id,input,gold_index,options,label 0,"Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected << rat D2 dopamine receptors >> (rD2(long)) by [[ quinpirole ]] had no effect. Query: What is the relation? activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line. Query: What is the relation? upregulator The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the << 5-HT(3/4)-receptor >> antagonist [[ tropisetron ]] did not affect it. Query: What is the relation? antagonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Query: What is the relation? substrate_product-of 8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor [[ bisindolylmaleimide I ]] (1 μM). Query: What is the relation? indirect-upregulator Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of [[ spermidine ]] and spermine with a significant accumulation of putrescine and induction of ODC. Query: What is the relation? product-of Dexamethasone (<< DEX >>), betamethasone (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]. Query: What is the relation? agonist Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats. Query: What is the relation? downregulator << Methionine synthase reductase >> (MTRR) is an enzyme involved in the conversion of [[ Hcy ]] to methionine. Query: What is the relation? substrate In contrast, zinc protoporphyrin (<< ZnPP >>), a specific [[ HO-1 ]] inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production. Query: What is the relation? inhibitor The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator Amrinone and << milrinone >>, selective PDE3 inhibitors, suppressed [[ TNF ]] secretion to a lesser extent. Query: What is the relation? indirect-downregulator Moreover, << geldanamycin >> decreases the amount and phosphorylation of Lck and Raf-1 [[ kinases ]] and prevents activation of the extracellular signal regulated kinase (ERK)-2 kinase. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 1,"Regarding the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and << midazolam >> (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively."", what is the relation? substrate Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Chronic insulin (24 h) activates NHE3 through the classic phosphatidylinositol 3-kinase-serum- and glucocorticoid-dependent kinase 1 (<< PI3K >>-SGK1) pathway as insulin stimulates SGK1 phosphorylation and the insulin effect can be blocked by the PI3K inhibitor [[ wortmannin ]] or a dominant-negative SGK1."", what is the relation? inhibitor Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""<< 2-(2-Aminoethyl)-quinoline >> (D-1997): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", what is the relation? agonist Regarding the sentence ""The data indicated that << PhIP >> could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and [[ c-jun ]] and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer."", what is the relation? activator Regarding the sentence ""CONCLUSIONS: In the maximum registered dosage, << nabumetone >> inhibits thromboxane production much more than meloxicam, signifying less [[ COX-2 ]] selectivity of the former."", what is the relation? downregulator Regarding the sentence ""Carnitine acetyltransferases (<< CrAT >>) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? product-of Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""Additionally, << AIF >> levels in the cytosol decreased due to [[ EGTA ]] but not due to calpeptin."", what is the relation? indirect-downregulator Regarding the sentence ""<< I3A >> induced a higher level of secretion of the inflammatory [[ cytokine ]] interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction."", what is the relation? indirect-upregulator Regarding the sentence ""CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", what is the relation? upregulator Regarding the sentence ""Effects of a << serotonin 5-HT(4) receptor >> antagonist [[ SB-207266 ]] on gastrointestinal motor and sensory function in humans."", what is the relation? antagonist Regarding the sentence ""Maqui berry (Aristotelia chilensis) and the constituent << delphinidin glycoside >> inhibit [[ photoreceptor ]] cell death induced by visible light."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 2,"Thus, in 158N cells, the ability of << oxysterols >> to trigger a mode of cell death by apoptosis involving [[ GSK-3 ]] and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains. Question: what is the relation? Answer: activator The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Question: what is the relation? Answer: agonist-activator The data show that CP[c]Ph is less potent at inducing << CYP1A >> gene expression in rainbow trout than benzo[a]pyrene ([[ B[a]P ]]), a well-known Ah-receptor agonist. Question: what is the relation? Answer: indirect-upregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Question: what is the relation? Answer: substrate_product-of << Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted ([[ DeltaKPQ ]]) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings. Question: what is the relation? Answer: downregulator Five classes of chalcogenopyrylium dyes (CGPs) were examined for their ability to modulate transport of << [(3)H]estradiol glucuronide >> (E217βG) (a prototypical [[ MRP ]] substrate) into MRP-enriched inside-out membrane vesicles. Question: what is the relation? Answer: substrate Two beta(2)-agonists, << formoterol >> and salmeterol, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity. Question: what is the relation? Answer: agonist Enalkiren (<< A-64662 >>), a potent, dipeptide renin inhibitor, mimics the transition state of the [[ human renin ]] substrate, angiotensinogen. Question: what is the relation? Answer: inhibitor << CGP 12177A >> mediates cardiostimulation by activation of the 'putative' beta(4)-adrenoceptor; however, it has recently been reported that disruption of the [[ beta(1)-adrenoceptor ]] gene abolishes this effect. Question: what is the relation? Answer: upregulator The inhibition of << UG >> synthesis and PR down-regulation by 5 alpha-NET and 3 beta,5 alpha-NET indicates that these [[ NET ]] metabolites possess antiprogestational properties. Question: what is the relation? Answer: indirect-downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor << Follicle-stimulating hormone >> (FSH), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex [[ steroids ]] and gametes. Question: what is the relation? Answer: product-of Terfenadine and astemizole are chemically unrelated to << histamine H1-receptor >> antagonists such as [[ diphenhydramine ]] and chlorpheniramine. Question: what is the relation? Answer: antagonist << Androgen >> antagonistic effect of estramustine phosphate (EMP) metabolites on wild-type and mutated [[ androgen receptor ]]. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 3,"Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""In comparison to diphenylhydantoin, the novel chloro-substituted << alpha-hydroxyphenylamide >> compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of [[ Na(V)1.5 ]] channels with an IC(50) value of 14.5 microM."". Can you identify the relation? inhibitor Consider the text ""The ultimate carcinogenic Phase I BP metabolite anti-BP-7,8-dihydrodiol-9,10-epoxide (BPDE) can be detoxified by << glutathione >> conjugate formation catalyzed by [[ glutathione S-transferases ]]."". Can you identify the relation? product-of Consider the text ""Thus, the << TCDD >>-induced reduction in canonical [[ Wnt ]] signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway."". Can you identify the relation? indirect-downregulator Consider the text ""<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and [[ catechol-O-methyltransferase ]] (COMT)."". Can you identify the relation? substrate Consider the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."". Can you identify the relation? agonist-activator Consider the text ""Chronic consumption of << alcohol >> also stimulated abrupt increases in pro-inflammatory cytokines such as nuclear factor (NF)-κB, [[ tumor necrosis factor (TNF)-α ]] and interleukin (IL)-1β in liver otherwise co-administration of CNF effectively suppressed production of these cytokines dose-dependently."". Can you identify the relation? activator Consider the text ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and [[ DNMT-3b ]]), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."". Can you identify the relation? downregulator Consider the text ""The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by << Tomudex >> indicate that increased cyclin E-[[ cdk2 ]] protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance."". Can you identify the relation? indirect-upregulator Consider the text ""In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the << CB2 >> antagonist AM630 [[[ (6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone) ]]]."". Can you identify the relation? antagonist Consider the text ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."". Can you identify the relation? upregulator Consider the text ""The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure."". Can you identify the relation? agonist Consider the text ""RESULTS: << GW572016 >> inhibited constitutive and/or ligand-induced [[ EGFR ]] or HER2 tyrosine phosphorylation of all five cell lines, which correlated with the antiproliferative response in all but one cell line."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 4,"Consider the text ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."". Can you identify the relation? agonist-activator Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""Phosphorylation of ER-stress marker << eIF2α >> was also increased but only at 30 min of [[ 2-deoxyglucose ]] exposure."". Can you identify the relation? activator Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""The use of << A3 receptor >> agonist [[ IB-MECA ]] attenuates EAP."". Can you identify the relation? agonist Consider the text ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system."". Can you identify the relation? product-of Consider the text ""The results show that CYP2E1 inhibits << CYP2B4 >>-mediated metabolism of benzphetamine ([[ BNZ ]]) with a K(i) of 0.04 µM."". Can you identify the relation? substrate Consider the text ""In combination with << clofarabine >>, the ability of resveratrol to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment."". Can you identify the relation? downregulator Consider the text ""In vitro, V(5+) decreased the << TCDD >>-mediated induction of [[ Cyp1a1 ]] mRNA, protein, and catalytic activity levels."". Can you identify the relation? indirect-upregulator Consider the text ""The estrogenic agent 3 beta,5 alpha-NET and << estradiol >> at a dose of 1.0 mg also inhibited the [[ UG ]] gene expression induced by P4."". Can you identify the relation? indirect-downregulator Consider the text ""<< Mazindol >> analogues as potential inhibitors of the [[ cocaine binding site ]] at the dopamine transporter."". Can you identify the relation? inhibitor Consider the text ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent << amino acid >> transporter, with functional features of [[ ASCT2 ]] transport."". Can you identify the relation? upregulator Consider the text ""The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the << 5-HT1A >> receptor antagonist [[ spiroxatrine ]] (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM)."". Can you identify the relation? antagonist Consider the text ""Affinity alkylation with 2 alpha-bromoacetoxyprogesterone suggests that the << dehydrogenase >> and isomerase substrate [[ steroids ]] bind at different sites on the same protein."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 5,"Regarding ""Here, we have now found that activation of p38 MAPK by << anisomycin >> potentiated induction of [[ CYP2B6 ]] mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes."", can you determine the relation? indirect-upregulator Regarding ""PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases (COX) and [[ prostaglandin E synthases ]] (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4)."", can you determine the relation? substrate Regarding ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", can you determine the relation? agonist-activator Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""To eliminate the interaction of << bupropion >> with DAT or [[ NET ]], nomifensine or desipramine, respectively, was included in the superfusion buffer."", can you determine the relation? inhibitor Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction."", can you determine the relation? antagonist Regarding ""Effect of ramelteon (<< TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor performance in mice."", can you determine the relation? agonist Regarding ""<< Dexamethasone >> suppresses histamine synthesis by repressing both transcription and activity of [[ HDC ]] in allergic rats."", can you determine the relation? indirect-downregulator Regarding ""We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase ([[ CHS ]]), and an antioxidant enzyme such as ascorbate peroxidase (APX)."", can you determine the relation? product-of Regarding ""At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of GluN1/[[ GluN2B ]] receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic."", can you determine the relation? downregulator Regarding ""Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα ([[ IκBα ]]) kinase, and inositol requiring enzyme 1α."", can you determine the relation? activator Regarding ""<< DEX >> enhanced the ratio [[ IFN-gamma ]]/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005)."", can you determine the relation? upregulator Regarding ""Unexpectedly, both the << mGluR(5) >>specific agonist, [[ CHPG ]], and the group II mGluR (mGlu(2/3)) agonist, LY379268 (LY), induced a TTX-insensitive outward current/hyperpolarization."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 6,"Regarding ""Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of << fisetin >> on [[ mTOR ]]."", can you determine the relation? downregulator Regarding ""The lysosomal inhibitor << chloroquine >> significantly increased [[ RCAN1 ]] accumulation in +/+ cells, consistent with the hypothesis that higher lysosomal pH impairs RCAN1 degradation, leading to a higher RCAN1/NFATc1 ratio and consequently NFATc1 inhibition."", can you determine the relation? indirect-upregulator Regarding ""CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of HDC gene expression and [[ HDC ]] activity in nasal mucosa plays an important role in the development of nasal hypersensitivity."", can you determine the relation? product-of Regarding ""PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates [[ phosphatidylinositol 4-phosphate ]] [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]."", can you determine the relation? substrate Regarding ""In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of << ethylmorphine-N-demethylase >> and aniline 4-hydroxylase activity and cytochrome P450, compared to the [[ CCl4 ]] only group."", can you determine the relation? activator Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or [[ methiothepin ]] (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction."", can you determine the relation? antagonist Regarding ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", can you determine the relation? substrate_product-of Regarding ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", can you determine the relation? upregulator Regarding ""There was no significant difference in << TLR4 >>, NF-κB, and IL-27 mRNA and proteins between [[ curcumin ]]-treated and sulfasalazine-treated groups."", can you determine the relation? indirect-downregulator Regarding ""OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a [[ peroxisome proliferator-activated receptor alpha ]] (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent."", can you determine the relation? agonist Regarding ""In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of << diphenylhydantoin >> and examined their ability to inhibit [[ human Na(V)1.5 ]] sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells."", can you determine the relation? inhibitor Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""Gemcitabine (<< dFdC >>, 2',2'-difluorodeoxycytidine) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase ([[ DCK ]]), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 7,"Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists terfenadine, astemizole, [[ loratadine ]], and acrivastine are reviewed."", describe the relation. antagonist Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""Previous studies demonstrated that the << Group III mGlu receptor >>-selective orthosteric agonist, [[ LSP1-2111 ]] produced anxiolytic- but not antidepressant-like effects upon peripheral administration."", describe the relation. agonist Given the text ""A dose of 25 microg kg(-1) day(-1) of << formoterol >> elicited greater EDL and soleus hypertrophy than salmeterol, but resulted in similar [[ beta-adrenoceptor ]] downregulation."", describe the relation. downregulator Given the text ""Conversely, AMPK inhibitor compound C or GSK3β inhibitor SB216763 blocked the cleavages of PARP and << caspase 3 >> induced by [[ ursolic acid ]] in HepG2 cells."", describe the relation. indirect-upregulator Given the text ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and [[ BT-05 ]] and BT-03 possessing asymmetric structure."", describe the relation. activator Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/[[ ERK ]] and Ras/mTOR pathways."", describe the relation. inhibitor Given the text ""These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of [[ p27(kip1) ]] expression and the increase in cyclin E and cdk2 kinase activities."", describe the relation. indirect-downregulator Given the text ""We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as [[ ascorbate peroxidase ]] (APX)."", describe the relation. product-of Given the text ""The alpha class << human GSTA4-4 >> enzyme (hGSTA4-4) has a particularly high catalytic efficiency toward [[ 4-HNE ]] conjugation."", describe the relation. substrate Given the text ""It has been reported that oligomeric << procyanidins >> of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and [[ insulin ]]-potentiating activities."", describe the relation. upregulator Given the text ""Valdecoxib potently inhibits recombinant << COX-2 >>, with an IC(50) of 0.005 microM; this compares with IC values of 0.05 microM for celecoxib, 0.5 microM for [[ rofecoxib ]], and 5 microM for etoricoxib."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 8,"Consider the text ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins ([[ MeCP-2 ]], MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."". Can you identify the relation? downregulator Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin ([[ TCDD ]]), the most potent activator of AhR."". Can you identify the relation? upregulator Consider the text ""In further studies, the diuretic effects of the << CB1 >> agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with [[ rimonabant ]], but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]."". Can you identify the relation? antagonist Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""The COX pathway generates inflammatory prostaglandins, while the << 5-LOX >> pathway generates inflammatory [[ leukotrienes ]]."". Can you identify the relation? product-of Consider the text ""After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist [[ 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium ]] (McN-A-343) and histamine."". Can you identify the relation? agonist Consider the text ""Taken together, << PTE >> is a potent inhibitor of osteosarcoma cell growth that targets the JAK2/[[ STAT3 ]] signaling pathway."". Can you identify the relation? inhibitor Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."". Can you identify the relation? agonist-activator Consider the text ""Upon co-exposure to V(5+) and TCDD, << V(5+) >> significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."". Can you identify the relation? indirect-upregulator Consider the text ""Polymorphisms in dopamine transporter (<< SLC6A3 >>) are associated with stimulant effects of [[ D-amphetamine ]]: an exploratory pharmacogenetic study using healthy volunteers."". Can you identify the relation? activator Consider the text ""Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, [[ NF-κB ]] p65 protein, and IL-27 p28 protein (p < 0.05)."". Can you identify the relation? indirect-downregulator Consider the text ""<< Carboxylesterases >> hydrolyze esters, [[ amides ]], and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively."". Can you identify the relation? substrate Consider the text ""With either substrate, << alendronate >> was a slow binding inhibitor of [[ PTPmeg1 ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 9,"The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator The << bupropion >> metabolic ratio appears to detect known differences in [[ CYP2B6 ]] activity associated with genetic polymorphism, across different ethnic groups. Please explain the relation. substrate Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. Please explain the relation. product-of One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Please explain the relation. substrate_product-of To determine whether dysregulation of SIRT1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of << SIRT1 >> ([[ nicotinamide ]], sirtinol, EX527) in aorta segments isolated from young Wistar rats. Please explain the relation. inhibitor Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Thus, it can be suggested that the inhibitory action of ginseng saponins against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking << norepinephrine >>- and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage rather than in the brain. Please explain the relation. indirect-upregulator The aim of the present study was to evaluate the cardiac effects of the << beta 3-adrenoceptor >> agonist [[ BRL35135 ]], and determine whether beta 3-receptors are involved in mediating chronotropic or inotropic responses in man. Please explain the relation. agonist Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, [[ MMP7 ]], and c-Myc. Please explain the relation. indirect-downregulator Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]. Please explain the relation. upregulator Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to << NRF2 >> inducers ([[ sulforaphane ]], tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments. Please explain the relation. activator Inhibition of binding of the << alpha2-receptor >> antagonist [[ [3H]RX821002 ]] to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro. Please explain the relation. antagonist Expression of the dominant negative mutants rab5A-<< N133I >> or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation. Please explain the relation. downregulator << Nicotinamide N-methyltransferase >> (NNMT) catalyses the conversion of nicotinamide to [[ 1-methylnicotinamide ]] and plays an important role in hepatic detoxification reactions. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 10,"Regarding ""Nitrogen-containing << bisphosphonates >> induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and [[ Bim ]]-mediated activation of the intrinsic apoptotic pathway."", can you determine the relation? activator Regarding ""However, combined treatment with << cinobufagin >> and SB216367 resulted in a significant reduction in [[ p65 ]] and an increase in cleaved-PARP in U2OS cells."", can you determine the relation? indirect-downregulator Regarding ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", can you determine the relation? agonist-activator Regarding ""The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the [[ Ras ]]/MEK/ERK and Ras/mTOR pathways."", can you determine the relation? inhibitor Regarding ""As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to metformin or [[ pioglitazone ]] and was noninferior to glipizide when added to metformin."", can you determine the relation? indirect-upregulator Regarding ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", can you determine the relation? substrate_product-of Regarding ""Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner."", can you determine the relation? upregulator Regarding ""Leukotriene A(4) hydrolase (<< LTA(4)H >>) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to [[ LTB(4) ]]."", can you determine the relation? product-of Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms."", can you determine the relation? downregulator Regarding ""The antagonistic property of << rilmenidine >> at [[ human alpha(2A)-adrenoceptors ]] indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved."", can you determine the relation? antagonist Regarding ""Both risperidone and << 9-hydroxyrisperidone >> are substrates of [[ P-glycoprotein ]] (P-gp), a transport protein involved in drug absorption, distribution, and elimination."", can you determine the relation? substrate Regarding ""At 10(-6)M in transcription assays, none of these compounds showed progestin agonist activity, whereas << mifepristone >> and its monodemethylated metabolite manifested slight [[ glucocorticoid ]] agonist activity."", can you determine the relation? agonist Regarding ""However, several promising nonpeptide, << vasopressin receptor >> antagonists have been described; these agents are VPA-985 ([[ lixivaptan ]]), YM-087 (conivaptan), OPC-41061 (tolvaptan), and SR-121463."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 11,"<< Orlistat >> is a new inhibitor of [[ pancreatic lipase ]] enzyme. Please explain the relation. inhibitor Pre-clinical pharmacology of << zolmitriptan >> (Zomig; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine. Please explain the relation. agonist These results suggest that << HSD11B1 >>-derived [[ cortisol ]] mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep. Please explain the relation. product-of Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized << KCNK1 >> as a [[ phenobarbital ]]-inducible antihyperplasia factor. Please explain the relation. activator CRH caused a rise in plasma ACTH after both loperamide (from 30 +/- 16.6 to a peak of 108 +/- 31 pmol/l) and placebo (from 98.5 +/- 47 to 211 +/- 61.7 pmol/l): the interaction between treatments and time was significant, and the first phase of << CRH >>-induced ACTH secretion was significantly lower after [[ loperamide ]]. Please explain the relation. downregulator Only pMPPI [<< 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride >>], a selective [[ 5-HT(1A) ]] antagonist, was effective in inhibiting all 5-HT syndrome behaviors produced by lisuride, whereas pMPPI was without effect on any behavior induced by LSD. Please explain the relation. antagonist Hydrogen sulphide (H(2)S) is synthesized from << L-cysteine >> via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS). Please explain the relation. substrate In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the << PGE1 >> mediated stimulation of [[ Na,K-ATPase beta ]] subunit gene transcription includes the stimulatory effect of 17-phenyl trinor PGE2, as well as the inhibitory effects of SC-51089. Please explain the relation. indirect-upregulator The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Please explain the relation. substrate_product-of Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Pyrrolidine dithiocarbamate (<< PDTC >>), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced [[ iNOS ]] expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity. Please explain the relation. indirect-downregulator Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (<< M/TPO-Ag >>) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis. Please explain the relation. upregulator << Pyridoxal kinase >> (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine, and [[ pyridoxine ]] in the presence of ATP and Zn2+. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 12,"In contrast, the << D-1997 >>-induced responses were potently and concentration-dependently antagonized by the mixed [[ 5-HT1-like ]] and 5-HT2 receptor antagonist methiothepin (0.01-1 microM). Please explain the relation. agonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor Selective antagonism of << GluR5 >> kainate-receptor-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons. Please explain the relation. antagonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Please explain the relation. agonist-activator In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and [[ Rspo3 ]]) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. Please explain the relation. indirect-downregulator Unlike mouse RetSat (mRetSat), << zRetSat A >> had an altered bond specificity saturating either the 13-14 or 7-8 double bonds of [[ all-trans-retinol ]] to produce either all-trans-13,14-dihydroretinol or all-trans-7,8-dihydroretinol, respectively. Please explain the relation. substrate At PND35, the medial prefrontal cortex (mPFC) of rats given << MPH >> showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase ([[ TH ]]), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density. Please explain the relation. indirect-upregulator << Aspirin >> (ASA) and other non-steroidal anti-inflammatory drugs, which are [[ cyclooxygenase ]] (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients. Please explain the relation. inhibitor Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Please explain the relation. upregulator Low levels of << serotonin >> may reduce the density of the serotonin transporter ([[ SERT ]]) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response"". Please explain the relation. downregulator In addition, PSE inhibited the transcriptional activity of NFAT without interfering with the << calcium >>-induced [[ NFAT ]] dephosphorylation event, which represents the major signaling pathway for its activation. Please explain the relation. activator Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues. Please explain the relation. product-of SK-Br3 cells cultured in the presence of topoisomerase IIalpha (<< TOP2A >>) inhibitors doxorubicin and etopoxide ([[ VP-16 ]]) demonstrated a 2- to 3-fold increase in FAS promoter activity when compared with control cells growing in drug-free culture conditions. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 13,"In reference to ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific)."", what is the relation? agonist In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, [[ cyclin dependent kinase 2 ]] (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator In reference to ""<< 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and Nrf-2-dependent [[ heme oxygenase-1 ]] induction."", what is the relation? activator In reference to ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator In reference to ""Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists."", what is the relation? antagonist In reference to ""Taken together, our results suggested that << Rg1 >> protected against Aβ25-35-induced apoptosis at least in part by two complementary GR-dependent ERK phosphorylation pathways: (1) down-regulating [[ HIF-1α ]] initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades."", what is the relation? indirect-downregulator In reference to ""However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]]."", what is the relation? indirect-upregulator In reference to ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by [[ thymidine phosphorylase ]] (TP) inside target tissues."", what is the relation? product-of In reference to ""Using a transient heterologous cell expression system, we find that the transport activities of the << short OATP2B1 >> variant towards substrates [[ estrone sulfate ]] and rosuvastatin are similar to the well-characterized full length variant."", what is the relation? substrate In reference to ""<< Miglustat >>, a small iminosugar molecule approved for the treatment of Gaucher disease, reversibly inhibits [[ glucosylceramide synthase ]], which catalyses the first committed step in glycosphingolipid synthesis."", what is the relation? inhibitor In reference to ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", what is the relation? upregulator In reference to ""<< Cabozantinib >> (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and [[ VEGF receptor 2 ]] (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 14,"The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. what is the relation? agonist-activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]. what is the relation? downregulator A series of phenolic acids and << phenol >> natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1). what is the relation? inhibitor Third, << ABCA1 >>-RNAi suppressed hepatic [[ alpha-tocopherol ]] secretion. what is the relation? product-of Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected rat D2 dopamine receptors (<< rD2 >>(long)) by [[ quinpirole ]] had no effect. what is the relation? activator OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of << FADS2 >> affects the PUFA biosynthetic pathway and consequently modifies the effect of [[ alpha-linolenic acid ]] (ALA) on myocardial infarction (MI). what is the relation? substrate << Conivaptan >>: a dual [[ vasopressin receptor v1a/v2 ]] antagonist [corrected]. what is the relation? antagonist The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure. what is the relation? agonist << Phillyrin >> strongly inhibited high glucose-induced fatty acid synthase ([[ FAS ]]) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation. what is the relation? indirect-downregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and [[ JNK1/2 ]] activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR. what is the relation? upregulator In this study, << aldosterone >> (ALD)-induced apoptosis of cardiomyocyte was evaluated based on the previous studies, and the roles of [[ calpain ]] signaling were clarified. what is the relation? indirect-upregulator << NFD >> abrogated EGF-induced phosphorylation of EGF receptor (EGFR) and phosphatidylinositol 3-kinase ([[ PI3K ]])/Akt. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 15,"Consider the text ""<< DXM >> and 1400W attenuated the mRNA expression of E-selectin and [[ iNOS ]] induced by the costimulation of reIL-4, reTNF-alpha, and LPS."". Can you identify the relation? indirect-downregulator Consider the text ""In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of ethylmorphine-N-demethylase and [[ aniline 4-hydroxylase ]] activity and cytochrome P450, compared to the CCl4 only group."". Can you identify the relation? activator Consider the text ""Compared with DM8W group, << SOD >> and ALDH2 in [[ EtOH ]]+DM8W group was increased, MDA was decreased."". Can you identify the relation? indirect-upregulator Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Labetalol (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the << isoprenaline >> responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors."". Can you identify the relation? agonist Consider the text ""<< COX-1 >> inhibition was measured as percentage inhibition of serum [[ TXB2 ]] generation in clotting whole blood, and as closure time with use of the platelet function analyser PFA-100."". Can you identify the relation? product-of Consider the text ""<< OMT >> showed partial protection in the cortical neurons via down-regulation of NR2B containing [[ NMDA receptors ]] and up-regulation of Bcl-2 family."". Can you identify the relation? downregulator Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""This study was conducted in order to understand the association between acute renal failure and the two << COX-2 >> inhibitors celecoxib and [[ rofecoxib ]]."". Can you identify the relation? inhibitor Consider the text ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."". Can you identify the relation? agonist-activator Consider the text ""Pretreatment with << tropisetron >> (1 microM), a [[ 5-HT3 ]] antagonist, ketanserin (10 microM), a 5-HT2 antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect."". Can you identify the relation? antagonist Consider the text ""It has been reported that oligomeric << procyanidins >> of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and [[ insulin ]]-potentiating activities."". Can you identify the relation? upregulator Consider the text ""Reductive detoxification of << arylhydroxylamine >> carcinogens by [[ human NADH cytochrome b5 reductase ]] and cytochrome b5."". Can you identify the relation? substrate Consider the text ""These findings are the first to show that long-term exposure to << Mn >> during a critical period of neurodevelopment causes motor coordination dysfunction with parallel increment in oxidative stress markers, [[ p38 ]](MAPK) phosphorylation and caspase activity in the striatum."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 16,"Given the text ""Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of sildenafil (<< Viagra >>, Pfizer) - the first approved selective [[ PDE ]] inhibitor for the treatment of ED."", describe the relation. inhibitor Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""4-Hydroxynonenal (<< 4-HNE >>) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several glutathione S-transferase ([[ GST ]]) isoforms."", describe the relation. substrate Given the text ""Discovery and optimization of << anthranilic acid sulfonamides >> as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of [[ albumin ]] binding."", describe the relation. downregulator Given the text ""The << TSA >>-induced [[ uc002mbe.2 ]] expression was positively correlated with the apoptotic effect of TSA in HCC cells."", describe the relation. indirect-upregulator Given the text ""Differences in magnitude of Na(+)-dependent << l-alanine >> uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", describe the relation. upregulator Given the text ""Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist AM1241 [[[ 1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole ]]], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects."", describe the relation. agonist Given the text ""(+)-Tamsulosin, (-)-tamsulosin, << SL 89,0591 >>, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]."", describe the relation. antagonist Given the text ""CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of [[ HDC ]] gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity."", describe the relation. product-of Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""<< Nox4 >> oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific [[ quinone ]] derivatives could modulate this activity."", describe the relation. activator Given the text ""There was no significant difference in << TLR4 >>, NF-κB, and IL-27 mRNA and proteins between curcumin-treated and [[ sulfasalazine ]]-treated groups."", describe the relation. indirect-downregulator Given the text ""Moreover, the effects of the DRD3 agonist << 7-hydroxy-N,N-dipropyl-2-aminotetralin >> (7-OH-DPAT)-induced locomotor hypoactivity were significantly increased when [[ DRD3 ]] proteins were abundant."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 17,"Question: What is the relation in the sentence ""The values of mean corpuscular << hemoglobin >> concentration and mean corpuscular hemoglobin increased in the [[ STX ]] group.""? indirect-upregulator Question: What is the relation in the sentence ""MXF or << VP-16 >> slightly affected cellular topo II activity in nuclear extracts derived from drug-treated cells while the combination enhanced inhibitory activity and the reduction in band depletion of [[ topo II ]].""? inhibitor Question: What is the relation in the sentence ""Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, [[ IL-27 ]] mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05).""? indirect-downregulator Question: What is the relation in the sentence ""Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line.""? upregulator Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and << sulprostone >> (an [[ EP3 ]]-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2.""? agonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted ([[ DeltaKPQ ]]) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings.""? downregulator Question: What is the relation in the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""These results indicate a major role of << CYP2B6 >> in [[ ketamine ]] N-demethylation in vitro and a significant impact of the CYP2B6*6 allele on enzyme-ketamine binding and catalytic activity.""? substrate Question: What is the relation in the sentence ""The potency of the antipsychotic drug, << risperidone >>, to antagonize alpha 1A-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of [[ alpha 1-adrenoceptor ]] subtype-discriminating antagonists.""? antagonist Question: What is the relation in the sentence ""The results reinforce previous assumptions that << dopamine >> may interact with eicosanoid metabolism by means of [[ D(2) receptor ]] activation, and implicate an involvement of cPLA(2) and COX-2 in this effect.""? activator Question: What is the relation in the sentence ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system.""? product-of Question: What is the relation in the sentence ""Reuptake of extracellular noradrenaline (<< NA >>) into superior cervical ganglion (SCG) neurones is mediated by means of the noradrenaline transporter ([[ NAT ]], uptake 1).""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 18,"Regarding the sentence ""The data show that CP[c]Ph is less potent at inducing << CYP1A >> gene expression in rainbow trout than benzo[a]pyrene ([[ B[a]P ]]), a well-known Ah-receptor agonist."", what is the relation? indirect-upregulator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Little is known in terms of multi-matrix << cytochrome P450 >> activity induction under repeated oral exposure to planar halogenated and polycyclic aromatic hydrocarbons (PHH, [[ PAH ]])."", what is the relation? activator Regarding the sentence ""The discovery of an inducible << oxidase >> whose apparent substrate preference is [[ spermine ]] indicates that polyamine catabolism is more complex than that originally proposed."", what is the relation? substrate Regarding the sentence ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", what is the relation? agonist-activator Regarding the sentence ""EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists ONO-AE3-208 and [[ AH 23848 ]], inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."", what is the relation? antagonist Regarding the sentence ""Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."", what is the relation? upregulator Regarding the sentence ""Our results demonstrated that << auranofin >> suppressed TLR4-mediated activation of transcription factors, NF-kappaB and [[ IRF3 ]], and expression of COX-2, a pro-inflammatory enzyme."", what is the relation? inhibitor Regarding the sentence ""After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full << muscarinic receptor >> agonist [[ methacholine ]], the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine."", what is the relation? agonist Regarding the sentence ""These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by SP-[[ NK-1R ]] related pathway in mouse pancreatic acinar cells."", what is the relation? product-of Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""<< Carvedilol >> reduced the risk of death or heart failure in patients with above-median levels of N-BNP or [[ adrenomedullin ]], or both, to rates not significantly different from those observed in patients with levels below the median value."", what is the relation? indirect-downregulator Regarding the sentence ""In addition, << ethanol >> induced degradation of DNA methyltransferases ([[ DNMT- ]]1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", what is the relation? downregulator Regarding the sentence ""We recently showed that << TETA >> is metabolized in vitro by polyamine catabolic enzyme spermidine/spermine-N(1)-acetyltransferase ([[ SSAT1 ]]) and by thialysine acetyltransferase (SSAT2) to its monoacetylated derivative (MAT)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 19,"OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (<< AR >>) agonist ([[ dexmedetomidine ]]). Question: what is the relation? Answer: agonist Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats. Question: what is the relation? Answer: upregulator The in vivo inhibitory effect of << harmaline >> on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified [[ CYP2D6 ]]. Question: what is the relation? Answer: downregulator A novel class of << biaryl urea >> that inhibits [[ C-RAF ]] kinase was discovered using a combination of medicinal and combinatorial chemistry approaches. Question: what is the relation? Answer: inhibitor Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while << 1400W dihydrochloride >> (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, [[ VEGF ]], and iNOS. Question: what is the relation? Answer: indirect-downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(<< WAF1 >>/CIP1) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2. Question: what is the relation? Answer: indirect-upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Question: what is the relation? Answer: agonist-activator Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the << phillyrin >>-enhanced activation of [[ AMPK ]] in HepG2 hepatocytes. Question: what is the relation? Answer: activator Pretreatment with << pranlukast >> (1.5 ng/mouse, intracerebroventricularly), a [[ CysLT(1)R ]] antagonist, blocked LTD4-induced amyloidogenesis, memory deficits. Question: what is the relation? Answer: antagonist Glycylsarcosine coadministration could inhibit the uptake of << cefadroxil >> in PEPT2(+/+) mice (p < 0.01) but not [[ PEPT2 ]](-/-) mice. Question: what is the relation? Answer: substrate We have shown that << COX-2 >> mediates acid-induced [[ PGE2 ]] production. Question: what is the relation? Answer: product-of The gastric mucin secretory responses to isoproterenol, furthermore, were inhibited by PP2, a selective inhibitor of tyrosine kinase Src responsible for ligand-independent EGFR autophosphorylation, but not by << ERK >> inhibitor, [[ PD98059 ]]. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 20,"Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""We now show that mutation of the 769R/ G desensitization site (Lomeli, H.M.J., Melcher, T., Hoger, T., Geiger, J.R., Kuner, T., Monyer, H., Higuchi, M.B.A. and Seeburg, P.H, Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science, 9(266) (1994) 1709-1713) greatly attenuates the << lithium >>-induced potentiation of [[ GluR3 ]]."", what is the relation? activator Regarding the sentence ""Ca(v)1.3 channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to << dihydropyridine >> (DHP) [[ L-VGCC ]] antagonists."", what is the relation? antagonist Regarding the sentence ""<< Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of [[ caspase 3 ]] and release of cytochrome c to the cytosol induced by DZN."", what is the relation? indirect-upregulator Regarding the sentence ""<< ATP-binding cassette transporter A1 >> is involved in hepatic [[ alpha-tocopherol ]] secretion."", what is the relation? product-of Regarding the sentence ""The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", what is the relation? agonist Regarding the sentence ""Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and [[ JNK1/2 ]] activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR."", what is the relation? upregulator Regarding the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and [[ retinoblastoma protein ]] (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator Regarding the sentence ""Using whole-cell voltage clamp, we examined << mibefradil >> block of four [[ Na+ channel ]] isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), Nav1.4 (skeletal muscle), Nav1.2 (brain), and Nav1.7 (peripheral nerve)."", what is the relation? inhibitor Regarding the sentence ""4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM [[ UGT1A6 ]] was about 10 times better catalyst than the other recombinant UGTs."", what is the relation? substrate Regarding the sentence ""<< Sulindac >> metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate cyclic GMP-dependent protein kinase (PKG); (b) activate c-jun NH2-terminal kinase (JNK); (c) inhibit extracellular signal-regulated kinase 1/2 (ERK1/2); and (d) decrease [[ beta-catenin ]] protein expression at times and doses consistent with apoptosis."", what is the relation? indirect-downregulator Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Late INa induced by the VGSC long QT mutant << R1623Q >> was reduced by [[ resveratrol ]] and quercetin."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 21,"Regarding the sentence ""The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, [[ alkaline phosphatase ]], total protein, albumin, bilirubin, cholesterol, urea and creatinine)."", what is the relation? indirect-upregulator Regarding the sentence ""Inhibition of << MCP-1 >> and MIP-2 transcription and translation by [[ mimosine ]] in muscle tissue infected with the parasite Trichinella spiralis."", what is the relation? indirect-downregulator Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Moreover, kinetic analysis revealed that inhibition by reserpine, a typical << VMAT2 >> inhibitor, was uncompetitive, decreasing maximum velocity and affinity for [[ dopamine ]]."", what is the relation? substrate Regarding the sentence ""Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]."", what is the relation? upregulator Regarding the sentence ""<< GPxs >> reduce hydroperoxides to the corresponding [[ alcohols ]] by means of glutathione (GSH)."", what is the relation? product-of Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase ([[ SOD ]]) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control."", what is the relation? downregulator Regarding the sentence ""Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, [[ doxazosin ]], prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials."", what is the relation? antagonist Regarding the sentence ""Phosphorylation of << AMPK >> at Thr172 increased by 1.4-fold within 5 min, and remained elevated throughout a 30-min time course, in response to [[ 2-deoxyglucose ]]."", what is the relation? activator Regarding the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", what is the relation? agonist-activator Regarding the sentence ""Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist AM1241 [[[ 1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole ]]], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects."", what is the relation? agonist Regarding the sentence ""We describe here the isolation and biochemical characterization of the marine natural << sesquiterpene >> palinurin as a [[ GSK-3β ]] inhibitor."", what is the relation? inhibitor Regarding the sentence ""<< Trichostatin A >> inhibits transforming growth factor-β-induced reactive oxygen species accumulation and myofibroblast differentiation via enhanced [[ NF-E2-related factor 2 ]]-antioxidant response element signaling."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 22,"Regarding the sentence ""In vitro, V(5+) decreased the << TCDD >>-mediated induction of [[ Cyp1a1 ]] mRNA, protein, and catalytic activity levels."", what is the relation? indirect-upregulator Regarding the sentence ""Pyrrolidine dithiocarbamate (<< PDTC >>), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced [[ iNOS ]] expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity."", what is the relation? indirect-downregulator Regarding the sentence ""Further, 5HHMF increased specific DNA-binding activity of << Nrf2 >>, and transient knockdown with Nrf2 siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity."", what is the relation? upregulator Regarding the sentence ""6-DHSG was metabolised by GSH to form a GSH conjugate (<< GS-6-DHSG >>) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of [[ glutathione-S-transferase ]] (GST)."", what is the relation? product-of Regarding the sentence ""A dose of 25 microg kg(-1) day(-1) of formoterol elicited greater EDL and soleus hypertrophy than << salmeterol >>, but resulted in similar [[ beta-adrenoceptor ]] downregulation."", what is the relation? downregulator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Independent of dietary choline, supplemental << Met >> increased hepatic [[ BHMT ]] activity approximately 30%."", what is the relation? activator Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and << oxymetazoline >>-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates."", what is the relation? agonist Regarding the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator Regarding the sentence ""The effects of meloxicam were compared with those of << diclofenac >>, a nonselective [[ COX ]] inhibitor."", what is the relation? inhibitor Regarding the sentence ""The potency of the antipsychotic drug, << risperidone >>, to antagonize [[ alpha 1A-adrenoceptor ]]-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 1-adrenoceptor subtype-discriminating antagonists."", what is the relation? antagonist Regarding the sentence ""<< QR2 >> catalyzes the two-electron reduction of menadione via the oxidation of N-alkylated or [[ N-ribosylated nicotinamides ]]."", what is the relation? substrate Regarding the sentence ""The next large phase III adjuvant trial for this subset of breast cancer is an international collaboration designed to evaluate the added or alternative benefit of an oral tyrosine kinase inhibitor targeting HER2/neu as well as the epidermal growth factor receptor (<< EGFR >>), [[ lapatinib ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 23,"In reference to ""On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]]."", what is the relation? upregulator In reference to ""Terbutaline (Bricanyl) and its prodrug << Bambuterol >> (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients."", what is the relation? agonist In reference to ""Both 5 alpha-NET and << 3 beta,5 alpha-NET >> blocked the [[ PR ]] down-regulation induced by P4 as assessed by Western and Northern blot methods."", what is the relation? indirect-upregulator In reference to ""In addition, << ethanol >> induced degradation of [[ DNA methyltransferases ]] (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", what is the relation? downregulator In reference to ""Specificity of << zebrafish retinol saturase >>: formation of all-trans-13,14-dihydroretinol and [[ all-trans-7,8- dihydroretinol ]]."", what is the relation? product-of In reference to ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets RAF/MEK/[[ ERK ]] pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature."", what is the relation? inhibitor In reference to ""Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 ([[ hCES1 ]]) and 2 (hCES2)."", what is the relation? substrate In reference to ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator In reference to ""We discovered that each RSPO alone or in combination partially rescues << TCDD >> inhibition of both canonical [[ Wnt ]] signaling and prostatic bud formation."", what is the relation? indirect-downregulator In reference to ""METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (<< SB-207266 >>) on the cisapride mediated increase in plasma aldosterone (a [[ 5-HT(4) ]] mediated response) and orocaecal transit in 18 subjects."", what is the relation? antagonist In reference to ""Effect of << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity on contractile receptor function in airway smooth muscle."", what is the relation? activator In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""The fact that << trimipramine >> also suppressed [[ IFN-gamma ]] production and T-cell proliferation indicates that these immunomodulatory actions of antidepressants are most likely unrelated to inhibition of monoamine reuptake."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 24,"Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively. Query: What is the relation? activator << Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α ([[ TNF-α ]]), inducible NO synthase (iNOS), and receptor for AGE (RAGE). Query: What is the relation? indirect-downregulator The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists SB224289 (300 microg/kg; 5-HT1B), << BRL15572 >> (300 microg/kg; [[ 5-HT1D ]]), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C). Query: What is the relation? antagonist The intrinsic clearance for both << ketamine >> enantiomers by the high affinity enzyme in HLMs with [[ CYP2B6*1 ]]/*1 genotype were at least 2-fold and 6-fold higher, respectively, than those for CYP2B6*1/*6 genotype and CYP2B6*6/*6 genotype. Query: What is the relation? substrate In conclusion, << IL-8 >> production and neutrophil infiltration are increased in high-[[ glucose ]] environment due to elevated ROS level and contributed to impaired wound healing in diabetic skin. Query: What is the relation? indirect-upregulator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Using a unique biosensor-based assay, << trifluoperazine >> (TFP) was identified as an inhibitor that disrupts the [[ S100A4 ]]/myosin-IIA interaction. Query: What is the relation? inhibitor Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats. Query: What is the relation? upregulator Third, << ABCA1 >>-RNAi suppressed hepatic [[ alpha-tocopherol ]] secretion. Query: What is the relation? product-of RGM-1 cells were treated with CDCA or << GW4064 >>, an [[ FXR ]] agonist, in the presence or absence of guggulsterone, an FXR antagonist. Query: What is the relation? agonist In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Query: What is the relation? agonist-activator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein ([[ pRb ]]), and the upregulation of p21(WAF1/CIP1) and p53. Query: What is the relation? downregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Galangin >> decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, [[ interleukin ]] (IL)-6, IL-1β, and IL-8. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 25,"Labetalol (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the << isoprenaline >> responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors. Query: What is the relation? agonist The TXM peptides were effective in inhibiting << AuF >>-induced MAPK, [[ JNK ]] and p38(MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation. Query: What is the relation? activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Query: What is the relation? substrate_product-of << TSA >> selectively induced [[ uc002mbe.2 ]] in four studied HCC cell lines. Query: What is the relation? indirect-upregulator It is concluded that << labetalol >> and dilevalol are [[ beta 1-adrenoceptor ]] selective antagonists. Query: What is the relation? antagonist << Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, [[ amines ]], and thiols, respectively. Query: What is the relation? product-of Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, [[ cyclin A ]], cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Query: What is the relation? downregulator Before the next drug intake, << MAO-A >> inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with [[ moclobemide ]] but not with toloxatone. Query: What is the relation? inhibitor << Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as [[ ketone ]] bodies. Query: What is the relation? substrate Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (SCF), and macrophage migration inhibitory factor (<< MIF >>)) were down-regulated by [[ artemisinic acid ]]. Query: What is the relation? indirect-downregulator The positive correlation between << vitamin A >> and immunoglobulin A concentrations might be the result of the vitamin A inductive effect during [[ immunoglobulins A ]] synthesis. Query: What is the relation? upregulator << Desvenlafaxine succinate >> identifies novel antagonist binding determinants in the [[ human norepinephrine transporter ]]. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 26,"Consider the text ""RESULTS: Ketorolac was six times more active against << COX-1 >> (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while [[ bromfenac ]] was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM)."". Can you identify the relation? downregulator Consider the text ""BACKGROUND AND AIMS: << Glutamic acid decarboxylase >> (GAD, EC 4.1.1.15) catalyses the conversion of [[ glutamate ]] to gamma-aminobutyric acid (GABA)."". Can you identify the relation? substrate Consider the text ""The effects of CDCA and GW4064 on expression of Cdx2 and << MUC2 >> were abolished by [[ guggulsterone ]]."". Can you identify the relation? indirect-downregulator Consider the text ""The beta-adrenergic/<< 5-HT1A >> receptor antagonist [[ (+/-)pindolol ]] and the selective 5-HT1B/D antagonist GR127935 produced no significant augmentation of venlafaxine-induced changes in either 5-HT or NA."". Can you identify the relation? antagonist Consider the text ""<< TSA >> selectively induced [[ uc002mbe.2 ]] in four studied HCC cell lines."". Can you identify the relation? indirect-upregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""These results suggest that << HSD11B1 >>-derived [[ cortisol ]] mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep."". Can you identify the relation? product-of Consider the text ""Both << tolbutamide >> and gliclazide stimulated [[ phospholipase C ]] activity; however, only gliclazide did so independently of its activity at K(ATP) channels, and this activity was partially inhibited by pertussis toxin."". Can you identify the relation? activator Consider the text ""The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure."". Can you identify the relation? agonist Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."". Can you identify the relation? agonist-activator Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""Synthesis, molecular modeling and evaluation of novel << N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone >> derivatives as dual inhibitors for cholinesterases and [[ Aβ ]] aggregation."". Can you identify the relation? inhibitor Consider the text ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively."". Can you identify the relation? upregulator Consider the text ""It is currently not known how much this << H(1) >> antagonism of [[ clozapine ]] contributes to the therapeutic or adverse side effects of clozapine."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 27,"The beta-adrenergic/<< 5-HT1A >> receptor antagonist [[ (+/-)pindolol ]] and the selective 5-HT1B/D antagonist GR127935 produced no significant augmentation of venlafaxine-induced changes in either 5-HT or NA. Please explain the relation. antagonist The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition. Please explain the relation. agonist RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Please explain the relation. agonist-activator Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of CA I and [[ CA II ]]. Please explain the relation. downregulator db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively. Please explain the relation. upregulator Expression of << L-type pyruvate kinase >> (L-PK) is upregulated in the liver by dietary [[ carbohydrate ]]. Please explain the relation. indirect-upregulator We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (<< PhIP >>; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5. Please explain the relation. substrate Overall, our findings suggest that << ursolic acid >> induced apoptosis in HepG2 cells via [[ AMPK ]] activation and GSK3β phosphorylation as a potent chemopreventive agent. Please explain the relation. activator Taken together, our study demonstrated that << SB365 >> inhibits the AKT/[[ mTOR ]] pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis. Please explain the relation. inhibitor Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor The << COX >> pathway generates inflammatory [[ prostaglandins ]], while the 5-LOX pathway generates inflammatory leukotrienes. Please explain the relation. product-of Epididymal tissue from wild-type mice responded in vitro to noradrenaline and << isoprenaline >> with increased glycerol release, reduced [[ IL-6 ]] release, and increased cAMP accumulation. Please explain the relation. indirect-downregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of The purified << Atp8a1 >> is inactive in detergent micelles or in micelles containing phosphatidylcholine, phosphatidic acid, or phosphatidylinositol, is minimally activated by [[ phosphatidylglycerol ]] or phosphatidylethanolamine (PE), and is maximally activated by PS. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 28,"<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ [[ glycogen synthase kinase 3β ]] (GSK-3β) signaling pathway. what is the relation? indirect-downregulator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of 8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by [[ tolbutamide ]] was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 μM). what is the relation? indirect-upregulator In concert with these results, we highlighted that the secretion of pro-inflammatory cytokine and << NF-κB >> activation induced by [[ TCDD ]] can be mediated by elevation of [Ca(2+)]i in HAPI microglial cells. what is the relation? activator It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a [[ BRCA2 ]] mutation. what is the relation? downregulator The M564G mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type << CrAT >>, and lower activity toward its natural substrate, [[ acetyl-CoA ]]. what is the relation? substrate The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. what is the relation? agonist-activator This stimulation was attenuated by the << Pak >> inhibitor 2,2'-dihydroxy-1,1'-dinaphthyldisulfide ([[ IPA3 ]]) or dominant-negative Pak1. what is the relation? inhibitor The << A2A adenosine receptor >> agonist CGS21680 ([[ C23H29N7O6.HCl.xH2O ]]) (0.001-0.1 μM) did not alter NE oxidation currents. what is the relation? agonist << DEX >> enhanced the ratio [[ IFN-gamma ]]/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). what is the relation? upregulator In contrast, there was little change in mRNA levels for GTP cyclohydrolase I (<< GTPCH >>), the rate limiting enzyme in synthesis of the [[ tetrahydrobiopterin ]] (BH4), the obligate cofactor for TPH. what is the relation? product-of Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists terfenadine, astemizole, [[ loratadine ]], and acrivastine are reviewed. what is the relation? antagonist Chromatographic analysis of the metabolism of << 14C-labeled arachidonic acid >> in this system revealed that PB-dependent inactivation of [[ PHS ]] is markedly increased in the presence of 100 microM H2O2. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 29,"Question: What is the relation in the sentence ""The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity.""? agonist Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Next to << Glut-4 >>, the predominant protein influencing [[ glucose ]] metabolism is PPARα and γ whose expressions were also positively modulated.""? substrate Question: What is the relation in the sentence ""The potent << histamine H(1)-receptor >> antagonist [[ cetirizine ]] (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine.""? antagonist Question: What is the relation in the sentence ""In conclusion, we find that << sinapic acid >> exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress [[ TGF-β1 ]] and its ability to attenuate activation of hepatic stellate cells.""? indirect-downregulator Question: What is the relation in the sentence ""6-Ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide (<< TAK-441 >>) is a potent, selective [[ hedgehog ]] signaling pathway inhibitor that binds to Smo and is being developed for the treatment of cancer.""? inhibitor Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]].""? agonist-activator Question: What is the relation in the sentence ""<< Mouse brain serine racemase >> catalyzes specific elimination of L-serine to [[ pyruvate ]].""? product-of Question: What is the relation in the sentence ""RESULTS: Ketorolac was six times more active against COX-1 (IC(50) = 0.02 microM) than << COX-2 >> (IC(50) = 0.12 microM) while [[ bromfenac ]] was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM).""? downregulator Question: What is the relation in the sentence ""Treatment of Rat-2 fibroblast cells with << C2-ceramide >> caused the stimulation of [[ c-fos SRE ]]-dependent reporter gene activity in a dose- and time-dependent manner by transient transfection analysis.""? activator Question: What is the relation in the sentence ""Cotreatments of 5, 10 and 20 µg/mL concentrations of MEP with << aflatoxin B(1) >> decreased the frequencies of SCE and the malondialdehyde level and increased amount of [[ superoxide dismutase ]], glutathione and glutathione peroxidase which were decreased by aflatoxin.""? indirect-upregulator Question: What is the relation in the sentence ""<< Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity.""? upregulator Question: What is the relation in the sentence ""Imatinib (STI571, << Gleevec >>, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, [[ PDGFRA ]], and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 30,"Question: What is the relation in the sentence ""<< Aliskiren >> represents the first in a novel class of [[ renin ]] inhibitors with the potential for treatment of hypertension and related cardiovascular diseases.""? inhibitor Question: What is the relation in the sentence ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.).""? upregulator Question: What is the relation in the sentence ""<< ORF 17583 >>, a [[ histamine H2-receptor ]] antagonist, inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 4.9 mg/kg intraduodenal; 3.4 mg/kg p.o.; and 0.21 mg/kg i.p.) and in total gastric fistula or Heidenhain pouch dogs stimulated by betazole (ED50 = 0.12 mg/kg p.o. and 0.08 mg/kg i.v.), histamine, tetragastrin, bethanechol, 2-deoxy-D-glucose or a meal (ED50 values ranged from 0.11-0.26 mg/kg p.o.).""? antagonist Question: What is the relation in the sentence ""In view of the role of CA in acid-base balance as well as the fact that an increase or decrease in its activity is accompanied by an increase or decrease in intra- and extracellular pH, our results suggest that: firstly, << CA >> activation induced by [[ indomethacin ]] might cause changes in COX activity; secondly, PGs are synthetized as a consequence of the changes in COX activity, a hypothesis that requires further study.""? activator Question: What is the relation in the sentence ""Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(WAF1/<< CIP1 >>) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2.""? indirect-upregulator Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].""? agonist-activator Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""Specifically, << hGSTA4 >> cells had significantly higher GSH concentrations when exposed to 5-15 microM 4-HNE, but not at 20 microM [[ 4-HNE ]], suggesting extensive GSH utilization at high concentrations of 4-HNE.""? substrate Question: What is the relation in the sentence ""Thus, << amitriptyline >> acts as a TrkA and [[ TrkB ]] agonist and possesses marked neurotrophic activity.""? agonist Question: What is the relation in the sentence ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and [[ MBD-3 ]]), in MEF cells by the proteasomal pathway.""? downregulator Question: What is the relation in the sentence ""Preincubation for 30 minutes with iloprost, << ciprostene >>, and carbacyclin led to a dose-dependent inhibition of [[ tissue factor ]] expression induced by all three challenging agents.""? indirect-downregulator Question: What is the relation in the sentence ""As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and << xanthine oxidase >> was identified as the likely source of TES-stimulated [[ superoxide ]] production.""? product-of Question: What is the relation in the sentence ""Upon studying the drug-drug interaction of darunavir with ketoconazole, data were indicative for an inhibitory effect of ketoconazole on << P-gp >> as the main mechanism for the increased transport of [[ darunavir ]] across the small intestine.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 31,"Second, << probucol >>, an antiatherogenic compound reported to be an inactivator of [[ ABCA1 ]] reduced hepatic alpha-tocopherol secretion. Question: what is the relation? Answer: downregulator The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the << alpha 1-adrenoceptor >> antagonist [[ prazosin ]] (0.01-1 microM). Question: what is the relation? Answer: antagonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase ([[ CAT ]]) activity compared with the control. Question: what is the relation? Answer: upregulator Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal << NGF >>, BDNF and ChAT that was eliminated by [[ olanzapine ]] treatment. Question: what is the relation? Answer: indirect-upregulator The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Question: what is the relation? Answer: agonist-activator One of the << CB2 >> agonists, [[ N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1,3,5-triazin-2-amine ]] (19, -logEC(50)=7.5, E(max)=255%) was selected for further development. Question: what is the relation? Answer: agonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and [[ Ras ]]/mTOR pathways. Question: what is the relation? Answer: inhibitor These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from << xanthine oxidase >>-generated [[ superoxide ]] and NO. Question: what is the relation? Answer: product-of In this study, we found that << 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of [[ inducible NO synthase ]] (iNOS) in BV2 microglia. Question: what is the relation? Answer: indirect-downregulator Under isotonic conditions, N-ethylmaleimide (<< NEM >>) produced [[ KCC ]] activation and transient cell shrinkage. Question: what is the relation? Answer: activator However, the loss of proliferative capacity of << hGSTA4 >> cells challenged with levels of [[ 4-HNE ]] associated with severe oxidative stress indicates a role of other aldehyde metabolizing enzymes, and/or GSH-electrophile transporter proteins, in providing full cellular protection against 4-HNE toxicity. Question: what is the relation? Answer: substrate RESULTS: Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective << COX-1 >>/COX-2 inhibitor, [[ ketorolac ]], resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 32,"RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. what is the relation? agonist-activator Extracellular application of << meclofenamate >> (EC(50) = 25 microM) and diclofenac (EC(50) = 2.6 microM) resulted in the activation of [[ KCNQ2/Q3 ]] K(+) currents, heterologously expressed in Chinese hamster ovary cells. what is the relation? activator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor RESULTS: Ketorolac was six times more active against << COX-1 >> (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while [[ bromfenac ]] was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM). what is the relation? downregulator << Licofelone >> almost abolished [[ 5-LOX ]] activity by inhibiting leukotriene B4 generation in rabbit neutrophils and prevented platelet thromboxane B2 production from whole blood. what is the relation? inhibitor Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity. what is the relation? upregulator << (+/-)-Tamsulosin >> effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of [[ alpha 1B-adrenoceptors ]] by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine. what is the relation? antagonist Thus, << amitriptyline >> acts as a TrkA and [[ TrkB ]] agonist and possesses marked neurotrophic activity. what is the relation? agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of Third, << ABCA1 >>-RNAi suppressed hepatic [[ alpha-tocopherol ]] secretion. what is the relation? product-of << Somatostatin >> which also inhibits [[ insulin ]] secretion was less efficient (inhibition by 20%). what is the relation? indirect-downregulator << Leukotriene D4 >> induces cognitive impairment through enhancement of CysLT₁ R-mediated [[ amyloid-β ]] generation in mice. what is the relation? indirect-upregulator One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (<< SHMT >>, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source. what is the relation? substrate Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 (MMP-13), [[ tissue inhibitor of metalloproteinase-1 ]] (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 33,"Regarding ""These findings suggest that << S1P >> activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of [[ osteoptotegerin ]] and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively."", can you determine the relation? indirect-upregulator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", can you determine the relation? agonist-activator Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""In membranes from HEK293 cells transfected with << alpha2-receptors >>, etomidate inhibited binding of the alpha2-antagonist, [[ [3H]RX821002 ]], with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm)."", can you determine the relation? antagonist Regarding ""4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (<< F >>, Cl, Br) derivatives are first-generation dual [[ aromatase ]] and sulfatase inhibitors (DASIs)."", can you determine the relation? inhibitor Regarding ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h."", can you determine the relation? upregulator Regarding ""Inhibition of mTOR by low dose << rapamycin >> decreases HG-induced [[ Nox4 ]] and Nox1, NADPH oxidase activity and podocyte apoptosis."", can you determine the relation? indirect-downregulator Regarding ""RGM-1 cells were treated with << CDCA >> or GW4064, an [[ FXR ]] agonist, in the presence or absence of guggulsterone, an FXR antagonist."", can you determine the relation? agonist Regarding ""OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of << FADS2 >> affects the [[ PUFA ]] biosynthetic pathway and consequently modifies the effect of alpha-linolenic acid (ALA) on myocardial infarction (MI)."", can you determine the relation? product-of Regarding ""The results reinforce previous assumptions that << dopamine >> may interact with eicosanoid metabolism by means of [[ D(2) receptor ]] activation, and implicate an involvement of cPLA(2) and COX-2 in this effect."", can you determine the relation? activator Regarding ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", can you determine the relation? substrate_product-of Regarding ""Concentration-dependent inhibitory effects of baicalin on the metabolism of << dextromethorphan >>, a dual probe of [[ CYP2D ]] and CYP3A, in rats."", can you determine the relation? substrate Regarding ""To determine whether 3,4-methylenedioxymethamphetamine (<< MDMA >>)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured."", can you determine the relation? downregulator Regarding ""The acetylation of << TETA >> is increased in [[ SSAT1 ]]-overexpressing mice compared with wild-type mice."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 34,"Question: What is the relation in the sentence ""To this end, 158N murine oligodendrocytes were treated with 7KC or << 7βOHC >> inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving [[ Mcl-1 ]], and caspase-3 activation.""? activator Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""Inhibition of mTOR by low dose << rapamycin >> decreases HG-induced [[ Nox4 ]] and Nox1, NADPH oxidase activity and podocyte apoptosis.""? indirect-downregulator Question: What is the relation in the sentence ""RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against [[ COX-2 ]] (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM).""? downregulator Question: What is the relation in the sentence ""Our results suggest that arsenite can potentiate EDHF-type relaxations via a mechanism that is dependent on hydrogen peroxide, thus demonstrating that dismutation of the << superoxide >> anion generated by [[ NADPH oxidase ]] can potentially offset loss of NO bioavailability under conditions of reduced eNOS activity.""? product-of Question: What is the relation in the sentence ""<< Nateglinide >> inhibits Kir6.2/SUR1 and [[ Kir6.2 ]]/SUR2B channels at 100 nM, and inhibits Kir6.2/SUR2A channels at high concentrations (1 microM).""? inhibitor Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""In addition to affecting << DAT >> function, MDMA rapidly decreased vesicular [[ DA ]] transport as assessed in striatal vesicles prepared from treated rats.""? substrate Question: What is the relation in the sentence ""Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (<< NK-1R >>), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells.""? indirect-upregulator Question: What is the relation in the sentence ""Previous studies demonstrated that the << Group III mGlu receptor >>-selective orthosteric agonist, [[ LSP1-2111 ]] produced anxiolytic- but not antidepressant-like effects upon peripheral administration.""? agonist Question: What is the relation in the sentence ""(+)-Tamsulosin, (-)-tamsulosin, << SL 89,0591 >>, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].""? antagonist Question: What is the relation in the sentence ""On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]].""? upregulator Question: What is the relation in the sentence ""Moreover, the specific << PKC >>-inhibitor [[ 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl) maleimide ]] (GF 109203X) markedly increased the potency and E(max) of isoprenaline for all conditions used, including control conditions, and the synergistic effects of PMA and fenoterol were completely prevented.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 35,"Question: What is the relation in the sentence ""<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), [[ NF-kB ]] p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin.""? indirect-downregulator Question: What is the relation in the sentence ""Expression of the dominant negative mutants arrestin-2(319-418) or dynamin I-K44A significantly reduced << U50,488H >>-induced down-regulation of the [[ hkor ]].""? downregulator Question: What is the relation in the sentence ""The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the << 5-HT(2A) >>-receptor antagonist [[ ketanserin ]] was without effect.""? antagonist Question: What is the relation in the sentence ""Vandetanib (<< Caprelsa >>(®), AstraZeneca) is a once-daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by growth-factor receptor tyrosine kinase RET (constitutively activated in roughly 60 % of all MTCs), vascular endothelial growth-factor receptors 2 and 3, and [[ epidermal growth-factor receptors ]].""? inhibitor Question: What is the relation in the sentence ""Activation of << ALDH2 >> with [[ ethanol ]] attenuates diabetes induced myocardial injury in rats.""? activator Question: What is the relation in the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol.""? agonist-activator Question: What is the relation in the sentence ""In the DRN, << brexpiprazole >> completely inhibited the firing of 5-HT neurons via [[ 5-HT1A ]] agonism and was more potent than aripiprazole (ED50 = 230 and 700 mug/kg, respectively).""? agonist Question: What is the relation in the sentence ""Here, we have determined the molecular mechanism of this male-specific activation of the << Kcnk1 >> gene and characterized KCNK1 as a [[ phenobarbital ]]-inducible antihyperplasia factor.""? indirect-upregulator Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""<< Uridine 5'-diphosphate- glucuronosyltransferases >> are colocalized with carboxylesterases and have the potential to further metabolize [[ carboxylic acids ]] to acyl glucuronides, but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases.""? substrate Question: What is the relation in the sentence ""We have previously reported that TZDs reduce << estrogen >> synthesis by inhibiting [[ aromatase ]] activity in human granulosa cells (HGC).""? product-of Question: What is the relation in the sentence ""To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance.""? upregulator Question: What is the relation in the sentence ""Among them, << nobiletin >> markedly inhibited [[ HGF ]]-induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and transwell-chamber invasion/migration assay under non-cytotoxic concentrations.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 36,"Given the text ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of << L-leucine >> for [[ leucine aminopeptidase ]], 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B."", describe the relation. substrate Given the text ""Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones [[ glucagon-like peptide-1 ]] and glucose-dependent insulinotropic polypeptide."", describe the relation. indirect-upregulator Given the text ""<< Tomudex >> treatment resulted in the decrease in [[ p27(kip1) ]] expression, with an increase in cyclin E and cdk2 protein expression and kinase activities 24 h after a 2-h exposure."", describe the relation. indirect-downregulator Given the text ""To further our understanding of how << fisetin >> negatively regulates [[ mTORC1 ]] signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells."", describe the relation. downregulator Given the text ""Two beta(2)-agonists, << formoterol >> and salmeterol, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity."", describe the relation. agonist Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""The positive correlation between << vitamin A >> and immunoglobulin A concentrations might be the result of the vitamin A inductive effect during [[ immunoglobulins A ]] synthesis."", describe the relation. upregulator Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""The acetylcholinesterase (AChE) and << butyrylcholinesterase >> (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), [[ 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline ]] (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described."", describe the relation. inhibitor Given the text ""Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system."", describe the relation. product-of Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""It was concluded that << PGE1 >> selectively reduces both N- and R-type Ca2+ currents by activating a [[ G-protein ]] probably through the EP3 receptor in paratracheal ganglion cells."", describe the relation. activator Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction."", describe the relation. antagonist Given the text ""Importantly, << 2-hydroxychalcone >> and xanthohumol exerted more potent inhibitory effects on the proliferation, [[ MMP-9 ]] expression and invasive phenotype of MDA-MB-231 than chalcone."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 37,"Regarding ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (<< 1O2 >>) donor chloramine T (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."", can you determine the relation? downregulator Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""<< Ozone >> plus PM(2.5) exposure, however, induced CRP, [[ IL-6 ]], CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way."", can you determine the relation? indirect-upregulator Regarding ""<< Memantine >> is an uncompetitive (channel blocking) [[ NMDA receptor ]] antagonist."", can you determine the relation? antagonist Regarding ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor [[ NF-κB ]], HSF1, AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins."", can you determine the relation? activator Regarding ""<< Thalidomide >> reduced [[ COX-2 ]] expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60."", can you determine the relation? indirect-downregulator Regarding ""<< Acetazolamide >>, a specific inhibitor of [[ CA ]], reduces the activity of CA I and CA II from red cells."", can you determine the relation? inhibitor Regarding ""However the regulatory mechanism of << histamine >> synthesis by [[ HDC ]] remains to be elucidated."", can you determine the relation? product-of Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM [[ UGT1A6 ]] was about 10 times better catalyst than the other recombinant UGTs."", can you determine the relation? substrate Regarding ""Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist acetylcholine ([[ ACh ]]) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump."", can you determine the relation? agonist Regarding ""G6pc2 deletion resulted in a leftward shift in the dose-response curve for << glucose >>-stimulated [[ insulin ]] secretion (GSIS)."", can you determine the relation? upregulator Regarding ""Blocking EGFR signaling with the EGFR/<< HER-2 >> kinase inhibitor (KI) [[ GW572016 ]] decreased the postradiation survival of irradiated Ras-transformed cells and normal cells but had no effect on the survival of unirradiated cells."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 38,"The potent << histamine H(1)-receptor >> antagonist cetirizine (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and [[ dextrocetirizine ]]. Query: What is the relation? antagonist Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Activation of an apoptotic signal transduction pathway involved in the upregulation of calpain and << apoptosis-inducing factor >> in [[ aldosterone ]]-induced primary cultured cardiomyocytes. Query: What is the relation? indirect-upregulator Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of [[ spermidine ]] and spermine with a significant accumulation of putrescine and induction of ODC. Query: What is the relation? product-of Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators ([[ Rspo2 ]] and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. Query: What is the relation? downregulator The current U.S. military and civilian oxime countermeasure, 2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium chloride (2-PAM), is under consideration for replacement with a more effective << acetylcholinesterase >> reactivator, 1,1'-methylenebis{4-hydroxyiminomethyl}pyridinium dimethanesulfonate ([[ MMB-4 ]]). Query: What is the relation? activator The mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes << tyrosinase >>, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment. Query: What is the relation? indirect-downregulator Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.). Query: What is the relation? upregulator We found that reduction of the carcinogenic << hydroxylamines >> of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5. Query: What is the relation? substrate First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive TOP2 poisons (e.g. doxorubicin, etoposide, mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive << TOP2 >> poisons (e.g. amonafide, batracylin, and [[ menadione ]]) was only slightly (less than 3-fold) affected. Query: What is the relation? inhibitor Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor Adenosine and N(6)-cyclopentyl-adenosine (<< CPA >>, [[ A1R ]] agonist) constricted MVs but not MAs. Query: What is the relation? agonist The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator To evaluate to what extent the regional differences in expression of P-gp and << P450 enzymes >> affect the absorption of a dual substrate, we investigated the transport of [[ darunavir ]] across different small intestinal segments (duodenum, proximal jejunum and ileum). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 39,"Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."". Can you identify the relation? agonist-activator Consider the text ""Liver << BHMT >> activity was 1.3-fold higher in rats fed the Met deficient diet containing [[ choline ]], which was reflected in corresponding increases in mRNA content and immunodetectable protein."". Can you identify the relation? indirect-upregulator Consider the text ""<< HSYA >> suppressed the expression of [[ TLR-4 ]], Myd88, ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells."". Can you identify the relation? indirect-downregulator Consider the text ""The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of [[ AchE ]] activity, CRP, NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level."". Can you identify the relation? upregulator Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system."". Can you identify the relation? product-of Consider the text ""Treatment with diclofenac resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated caspase-3 after 6 hr, indicating that << diclofenac >> may cause apoptosis of neuronal cells via activation of the [[ caspase ]] cascade."". Can you identify the relation? activator Consider the text ""Moreover, recent in vitro studies suggest that << memantine >> abrogates [[ beta-amyloid ]] (Abeta) toxicity and possibly inhibits Abeta production."". Can you identify the relation? downregulator Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""<< Acarbose >>, an [[ alpha-glucosidase ]] inhibitor, delays the absorption of carbohydrate from the small intestine, thereby reducing postprandial hyperglycemia."". Can you identify the relation? inhibitor Consider the text ""Pre-clinical pharmacology of << zolmitriptan >> (Zomig; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine."". Can you identify the relation? agonist Consider the text ""The anticonvulsant << felbamate >> blocks N-methyl-D-asparate (NMDA) receptors but fails to exhibit the neurobehavioral toxicity characteristic of other [[ NMDA receptor ]] antagonists."". Can you identify the relation? antagonist Consider the text ""<< SR-BI >> is a receptor that binds HDL with high affinity and mediates both the selective lipid uptake of cholesteryl esters from lipid-rich HDL to cells and the efflux of unesterified [[ cholesterol ]] from cells to HDL."". Can you identify the relation? substrate Consider the text ""Most of the tested H(2)R agonists and << imidazole >>-based H(3)R ligands show micromolar-to-nanomolar range hH(4)R affinity, and these ligands exert different intrinsic [[ hH(4)R ]] activities, ranging from full agonists to inverse agonists."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",12,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist-inhibitor 40,"The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator The ARB << eprosartan >> is a nonbiphenyl nontetrazole [[ angiotensin II type 1 receptor ]] (AT1) antagonist, which acts to decrease total peripheral resistance. Please explain the relation. antagonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Please explain the relation. substrate_product-of In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor Galanin attenuates cyclic AMP regulatory element-binding protein (<< CREB >>) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures. Please explain the relation. activator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, [[ cyclin dependent kinase 2 ]] (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Please explain the relation. downregulator Sumatriptan and << LY 344864 >> decreased the number of capsaicin-induced [[ c-fos ]]-like immunoreactive cells within trigeminal nucleus caudalis (ID50 = 0.04 and 0.6 mg kg(-1)). Please explain the relation. indirect-downregulator Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons ([[ PAHs ]]), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis. Please explain the relation. substrate In addition to CYP2B6, << anisomycin >> co-treatment potentiated an increase in CYP2A7 and [[ CYP2C9 ]] mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs. Please explain the relation. indirect-upregulator First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive << TOP2 >> poisons (e.g. doxorubicin, etoposide, [[ mitoxantrone ]], and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected. Please explain the relation. inhibitor Follicle-stimulating hormone (<< FSH >>), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex [[ steroids ]] and gametes. Please explain the relation. product-of Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells. Please explain the relation. upregulator After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and [[ histamine ]]. Please explain the relation. agonist Fenofibrate and << GW2331 >> induced expression of acyl-coenzyme A (CoA) oxidase and [[ enoyl-CoA hydratase ]] and reduced apolipoprotein C-III and phosphoenolpyruvate carboxykinase mRNAs. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 41,"Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and mTOR via suppression of [[ Ras ]] prenylation and enhanced Bim expression. Query: What is the relation? inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Query: What is the relation? substrate_product-of Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Query: What is the relation? upregulator We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and [[ chalcone synthase ]] (CHS), and an antioxidant enzyme such as ascorbate peroxidase (APX). Query: What is the relation? product-of In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, [[ DNMT-3a ]], and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Query: What is the relation? downregulator In the present study, we investigated the effect of << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity on muscarinic receptor agonist- and histamine-induced bovine tracheal smooth muscle contractions. Query: What is the relation? activator The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals. Query: What is the relation? antagonist The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator In conclusion, the production of IL-4 and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by << DEX >> than that of [[ IFN-gamma ]], which may account for the therapeutic effects of glucocorticosteroids in patients with asthma. Query: What is the relation? indirect-downregulator Indoleamine 2,3-dioxygenase (<< IDO >>), a [[ tryptophan ]] catabolizing enzyme, has been implicated in the pathogenesis of various neurological disorders. Query: What is the relation? substrate Furthermore, the up-regulation of << IL-12 >> and TNF-α was found in the [[ procyanidin ]] trimers-treated cells in the presence of OVA. Query: What is the relation? indirect-upregulator Thus, << amitriptyline >> acts as a [[ TrkA ]] and TrkB agonist and possesses marked neurotrophic activity. Query: What is the relation? agonist Here, we show that at noncytotoxic concentrations, << H(2)S >> was able to inhibit NO production and inducible NO synthase ([[ iNOS ]]) expression via heme oxygenase (HO-1) expression in RAW264.7 macrophages stimulated with lipopolysaccharide (LPS). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 42,"The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). what is the relation? agonist In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport. what is the relation? upregulator As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to metformin or pioglitazone and was noninferior to glipizide when added to [[ metformin ]]. what is the relation? indirect-downregulator Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity. what is the relation? downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Here, we have now found that activation of p38 << MAPK >> by [[ anisomycin ]] potentiated induction of CYP2B6 mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes. what is the relation? indirect-upregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists ONO-AE3-208 and [[ AH 23848 ]], inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth. what is the relation? antagonist Moreover, activities of caspase-3 and << caspase-9 >> enzymes were also significantly higher in both kinds of cells exposed to [[ SiO(2) ]] NPs. what is the relation? activator << Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, [[ pyruvate ]], as well as ketone bodies. what is the relation? substrate Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]]. what is the relation? product-of Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), << kurarinol >> ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]). what is the relation? inhibitor << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. what is the relation? agonist-activator Under voltage-clamp conditions, << cisapride >> block of [[ HERG ]] is dose dependent with a half-maximal inhibitory concentration of 6.5 nM at 22 degrees C (n = 25 cells). what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 43,"Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of Correlation between activation of PPARγ and << resistin >> downregulation in a mouse adipocyte cell line by a series of [[ thiazolidinediones ]]. Question: what is the relation? Answer: downregulator Structural features of the central cannabinoid CB1 receptor involved in the binding of the specific << CB1 >> antagonist [[ SR 141716A ]]. Question: what is the relation? Answer: antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of arginine with << rhArg >>, to [[ citrulline ]], which is converted back to arginine via ASS. Question: what is the relation? Answer: product-of In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: agonist-activator Systemic administration of << beta2-adrenoceptor >> agonists, formoterol and [[ salmeterol ]], elicit skeletal muscle hypertrophy in rats at micromolar doses. Question: what is the relation? Answer: agonist In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport. Question: what is the relation? Answer: upregulator Pretreatment of human breast carcinoma MCF-7 cells for 24 h with the groundnut extract and soybean << isoflavone >> increased gene expression of [[ heme oxygenase-1 ]] (HO-1), a major antioxidative stress enzyme. Question: what is the relation? Answer: indirect-upregulator Several active analogues were also evaluated for their ability to block uptake of DA, << 5-HT >>, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-[[ hSERT ]], and HEK-hNET cells. Question: what is the relation? Answer: substrate These findings suggest that the anti-allodynia effect of << CP-101,606 >> is ascribable to blockade of [[ NR2B ]] receptors at the brain, but not at the spinal cord. Question: what is the relation? Answer: inhibitor The treatment of mice with << Fe-NTA >> alone enhances [[ ornithine decarboxylase ]] activity to 4.6 folds, protein carbonyl formation increased up to 2.9 folds and DNA synthesis expressed in terms of [(3)H] thymidine incorporation increased to 3.2 folds, and antioxidants and antioxidant enzymes decreased to 1.8-2.5 folds, compared with the corresponding saline-treated controls. Question: what is the relation? Answer: activator Inhibition of human iNOS promoter-driven luciferase activity by << gemfibrozil >> in cytokine-stimulated U373MG astroglial cells suggests that this compound inhibits the transcription of [[ iNOS ]]. Question: what is the relation? Answer: indirect-downregulator RESULTS: Rolipram unmasked the inhibitory effect of << beta(2)-adrenoceptor >> stimulation with [[ salmeterol ]] and significantly attenuated the stimulated release of AA and subsequent LTC(4). Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 44,"In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of [[ R-spondins ]] (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. Query: What is the relation? indirect-downregulator On the other hand, treatment with << gentianine >> significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-γ, GLUT-4 and [[ adiponectin ]]. Query: What is the relation? indirect-upregulator A series of 2-carbonyl analogues of the muscarinic antagonist << diphenidol >> bearing 1-substituents of different lipophilic, electronic, and steric properties was synthesized and their affinity for the [[ M2 and M3 muscarinic receptor ]] subtypes was evaluated by functional tests. Query: What is the relation? antagonist << Amitriptyline >> is a TrkA and [[ TrkB ]] receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Query: What is the relation? agonist The chemical identity and position of the substituents on the lower << aniline >> ring were important in determining the potency and extent of [[ COX ]] inhibition as well as COX-2 selectivity. Query: What is the relation? inhibitor G6pc2 deletion resulted in a leftward shift in the dose-response curve for << glucose >>-stimulated [[ insulin ]] secretion (GSIS). Query: What is the relation? upregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, [[ TMB-4 ]] and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. Query: What is the relation? activator Polyclonal antisera to either << b5R >> or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl ([[ NHOH-4-ABP ]]) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP). Query: What is the relation? substrate One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Query: What is the relation? substrate_product-of Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. Query: What is the relation? product-of Previously, we showed that the << human kappa-opioid receptor >> (hkor) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged [[ U50,488H ]] treatment. Query: What is the relation? downregulator In a human whole blood assay, IC(50) values for << lumiracoxib >> were 0.13 microM for COX-2 and 67 microM for COX-1 ([[ COX-1 ]]/COX-2 selectivity ratio 515). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 45,"In reference to ""Thus, in 158N cells, the ability of << oxysterols >> to trigger a mode of cell death by apoptosis involving [[ GSK-3 ]] and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains."", what is the relation? activator In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of AchE activity, CRP, NF-κB, and [[ MCP-1 ]] accompanied with a significant depletion in the Ach level."", what is the relation? indirect-upregulator In reference to ""(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and << RS 17053 >> appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]."", what is the relation? antagonist In reference to ""BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, << EC 4.1.1.15 >>) catalyses the conversion of [[ glutamate ]] to gamma-aminobutyric acid (GABA)."", what is the relation? substrate In reference to ""Here we report the re-engineering of << navitoclax >> to create a highly potent, orally bioavailable and [[ BCL-2 ]]-selective inhibitor, ABT-199."", what is the relation? inhibitor In reference to ""To determine whether << 3,4-methylenedioxymethamphetamine >> (MDMA)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured."", what is the relation? downregulator In reference to ""<< Phillyrin >> strongly inhibited high glucose-induced fatty acid synthase ([[ FAS ]]) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation."", what is the relation? indirect-downregulator In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Evidence has accumulated in the last few years that the expression of the << microsomal/peroxidase antigen >> (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis."", what is the relation? upregulator In reference to ""<< Mouse brain serine racemase >> catalyzes specific elimination of L-serine to [[ pyruvate ]]."", what is the relation? product-of In reference to ""<< H1-receptor >> antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which [[ histamine ]] is considered to be of pathogenic importance and conversely to help elucidate the role of histamine in disease, through an evaluation of their influence on disease expression."", what is the relation? agonist In reference to ""Valdecoxib potently inhibits recombinant << COX-2 >>, with an IC(50) of 0.005 microM; this compares with IC values of 0.05 microM for [[ celecoxib ]], 0.5 microM for rofecoxib, and 5 microM for etoricoxib."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 46,"The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase ([[ GPx ]]) activities, while increased catalase (CAT) activity compared with the control. what is the relation? downregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). what is the relation? substrate_product-of The potent << histamine H(1)-receptor >> antagonist [[ cetirizine ]] (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine. what is the relation? antagonist Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and << sulprostone >> (an [[ EP3 ]]-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. what is the relation? agonist Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin ([[ TCDD ]]), the most potent activator of AhR. what is the relation? upregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. what is the relation? agonist-activator Kinetic constants of the mutant << CrAT >> showed modification in favor of longer [[ acyl-CoAs ]] as substrates. what is the relation? substrate Compared with aripiprazole, which significantly inhibited the firing activity of VTA DA neurons, << brexpiprazole >> displayed less efficacy at [[ D2 receptors ]]. what is the relation? indirect-downregulator << Epi >> increased both WNT6/[[ Wnt6 ]] and Cav1 expression in human GC cells and within the tumor area of a murine model of GC (CEA424-SV40 TAg). what is the relation? indirect-upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor On the basis of FIP1L1-PDGFRa fusion gene hypereosinophilic syndrome would be classified as a clonal disease and in the FIP1L1-PDGFRa positive cases the << tyrosine kinase >> inhibitor [[ imatinib mesylate ]] (Glivec) would be effective. what is the relation? inhibitor To determine whether dysregulation of SIRT1 promotes << NADPH oxidase >>-dependent production of reactive [[ oxygen ]] species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of SIRT1 (nicotinamide, sirtinol, EX527) in aorta segments isolated from young Wistar rats. what is the relation? product-of << 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and [[ Nrf-2 ]]-dependent heme oxygenase-1 induction. what is the relation? activator Moreover, << geldanamycin >> decreases the amount and phosphorylation of [[ Lck ]] and Raf-1 kinases and prevents activation of the extracellular signal regulated kinase (ERK)-2 kinase. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 47,"Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal << NGF >>, BDNF and ChAT that was eliminated by [[ olanzapine ]] treatment."", describe the relation. indirect-upregulator Given the text ""Dexamethasone (DEX), betamethasone (<< BM >>), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]."", describe the relation. agonist Given the text ""Cotreatment with U0126 and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of << sulindac >> treatment on ERK1/2, [[ JNK ]], and beta-catenin."", describe the relation. activator Given the text ""One major route involves the tetrahydrofolate (THF)-dependent activities of the << glycine decarboxylase complex >> (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source."", describe the relation. substrate Given the text ""Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and << BMY-7378 >> (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective [[ alpha(1D)-adrenoceptor ]] antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively)."", describe the relation. antagonist Given the text ""Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS."", describe the relation. product-of Given the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", describe the relation. agonist-activator Given the text ""Additionally, the mRNA levels of melanogenesis-related genes (<< c-KIT >>, stem cell factor (SCF), and macrophage migration inhibitory factor (MIF)) were down-regulated by [[ artemisinic acid ]]."", describe the relation. indirect-downregulator Given the text ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity."", describe the relation. upregulator Given the text ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase ([[ GPx ]]) activities, while increased catalase (CAT) activity compared with the control."", describe the relation. downregulator Given the text ""Indomethacin inhibited both hCOX-1 and hCOX-2, whereas << NS-398 >> and Dup-697 selectively inhibited [[ hCOX-2 ]]."", describe the relation. inhibitor Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", describe the relation. substrate_product-of Given the text ""Currently, the most important insecticides are << neonicotinoids >>, which are metabolized in vitro by [[ AOX ]] on reduction of the nitroimino group and by CYPs via oxidation reactions."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 48,"Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512).""? upregulator Question: What is the relation in the sentence ""Taken together, our findings indicate that << 5HHMF >> suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of [[ Nrf2 ]]-dependent HO-1 activity.""? activator Question: What is the relation in the sentence ""<< Aldosterone >>-induced [[ ENaC ]] and basal Na(+)/K(+)-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIIIβ trans Golgi signalling in M1 cortical collecting duct cells.""? indirect-upregulator Question: What is the relation in the sentence ""The purified human enzyme also does not oxidize eight representative antitumor polyamine analogues; however, specific oligamine analogues were found to be potent inhibitors of the oxidation of << spermine >> by PAOh1/[[ SMO ]].""? substrate Question: What is the relation in the sentence ""Terfenadine and << astemizole >> are chemically unrelated to [[ histamine H1-receptor ]] antagonists such as diphenhydramine and chlorpheniramine.""? antagonist Question: What is the relation in the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Everolimus (<< RAD001 >>, Afinitor((R)) Novartis) is the first oral inhibitor of [[ mTOR ]] (mammalian target of rapamycin) to reach the oncology clinic.""? inhibitor Question: What is the relation in the sentence ""Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, [[ NF-κB ]] p65 protein, and IL-27 p28 protein (p < 0.05).""? indirect-downregulator Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""PIP5K1B encodes << phosphatidylinositol 4-phosphate 5-kinase β type I >> (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2].""? product-of Question: What is the relation in the sentence ""However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of [[ metallothionein-II ]] production, and an increase in p53 activation and the pro-apoptotic protein Bax.""? downregulator Question: What is the relation in the sentence ""Terbutaline (<< Bricanyl >>) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients.""? agonist Question: What is the relation in the sentence ""The potent anabolic effects of the << beta 2-adrenoceptor >> agonist [[ clenbuterol ]] on skeletal muscle have been reported to be independent of actions on beta-adrenoceptors.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 49,"One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (<< GDC >>, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source. what is the relation? substrate RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. what is the relation? agonist-activator Effects of a << serotonin 5-HT(4) receptor >> antagonist [[ SB-207266 ]] on gastrointestinal motor and sensory function in humans. what is the relation? antagonist Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. what is the relation? downregulator Two beta(2)-agonists, << formoterol >> and salmeterol, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity. what is the relation? agonist The ROS scavenger << N-acetyl l-cysteine >> and the mitochondrial antioxidant Mito-TEMPO rescued the inhibitory effect of cucurbitacin I on [[ Rac1 ]] activation. what is the relation? activator Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]. what is the relation? upregulator A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the VEGFR << tyrosine kinase >> inhibitors [[ sunitinib ]] and/or sorafenib. what is the relation? inhibitor Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of Suppression of TβR1 by the pharmacological inhibitor (<< SB431542 >>) markedly reduced [[ VEGF ]] release by HFL-1 in response to CSE and this effect was confirmed by TβR1 siRNA. what is the relation? indirect-downregulator These results indicate transcription of << FDX1 >> is regulated by the NR5A family and [[ cAMP ]] signaling, and participates in steroid hormone production in ovarian granulosa cells. what is the relation? indirect-upregulator << PGE(2) >> is synthesized from arachidonic acid by [[ cyclooxygenases ]] (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). what is the relation? product-of In addition, << sorafenib >> demonstrated significant activity against several receptor tyrosine kinases involved in neovascularization and tumor progression, including vascular-endothelial growth factor (VEGFR)-2, [[ VEGFR-3 ]], platelet-derived growth factor (PDGFR)-beta Flt-3, and c-KIT. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",6,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",upregulator 50,"The identification of the succinate receptor << SUCNR1 >> in platelets is of particular interest, because physiologically relevant concentrations of [[ succinate ]] were shown to potentiate the effect of low doses of a variety of platelet agonists. Please explain the relation. agonist We also found that << TRPV1 >> receptors are activated by [[ CuSO(4) ]], ZnSO(4), and FeSO(4), three salts known to produce a metallic taste sensation. Please explain the relation. activator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of These findings demonstrate that cinnamon << polyphenols >> can exert the hypoglycemic and hypolipidemic effects through the mechanisms that may be associated with repairing pancreatic beta cells in diabetic mice and improving its anti-oxidative capacity, as well as attenuating cytotoxicity via inhibition of [[ iNOS ]], NF-κB activation. Please explain the relation. inhibitor One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, << EC 2.1.1.10 >>) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source. Please explain the relation. substrate Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor Apple << polyphenols >> suppress antigen presentation of [[ ovalbumin ]] by THP-1-derived dendritic cells. Please explain the relation. downregulator Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]. Please explain the relation. upregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator Inhibition of << SIRT1 >> significantly increased vascular [[ superoxide ]] production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by resveratrol. Please explain the relation. product-of Selective antagonism of << GluR5 >> kainate-receptor-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons. Please explain the relation. antagonist Exposure to << PAHs >>, their metabolites, and ROS further increase [[ AKRs ]] isoform expression that may amplify oxidative damage. Please explain the relation. indirect-upregulator << NaAsO(2) >> increased the mRNA levels of the light and medium subunits of neurofilament and decreased the mRNA levels of tau and [[ tubulin ]] in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin. Please explain the relation. indirect-downregulator Formation of pyruvate by << SDH >> is a two-step reaction in which the hydroxyl group of serine is cleaved to produce [[ aminoacrylate ]], and then the aminoacrylate is deaminated by nonenzymatic hydrolysis to produce pyruvate. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 51,"Consider the text ""The structure-activity relationships revealed that the free hydroxyl group at position 5 and phosphate group at position 7 of the << phosphorylated flavonoids >> are favorable to the inhibition of [[ CEase ]]."". Can you identify the relation? inhibitor Consider the text ""Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected << rat D2 dopamine receptors >> (rD2(long)) by [[ quinpirole ]] had no effect."". Can you identify the relation? activator Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Even though the activities of MAT and << GNMT >> were elevated, the concentration of liver S-adenosylmethionine was decreased (24%, p<0.001) and [[ S-adenosylhomocysteine ]] increased (113%, p<0.001) in the dwarf mice."". Can you identify the relation? product-of Consider the text ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of [[ VEGF ]]and MMP-9, resulting from the inhibition of Akt pathway."". Can you identify the relation? downregulator Consider the text ""The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and << 5-HT4 >> receptor antagonist ICS205930 ([[ tropisetron ]]; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM)."". Can you identify the relation? antagonist Consider the text ""I3A induced a higher level of secretion of the inflammatory << cytokine >> interleukin 6 compared with [[ PMA ]] in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction."". Can you identify the relation? indirect-upregulator Consider the text ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively."". Can you identify the relation? upregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""Furthermore, << V(5+) >> significantly inhibited the TCDD-induced [[ AhR ]]-dependent luciferase activity."". Can you identify the relation? indirect-downregulator Consider the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."". Can you identify the relation? agonist-activator Consider the text ""Injections of << m-CPBG >>, a selective [[ 5-HT3 ]] receptor agonist, induced a significant increase in blood glucose in non-stressed rats in both fasted and in fed states."". Can you identify the relation? agonist Consider the text ""In conclusion, immortalized SHR and WKY PTE cells take up << l-alanine >> mainly through a high-affinity Na(+)-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport."". Can you identify the relation? substrate Consider the text ""Fragment-based drug design and identification of << HJC0123 >>, a novel orally bioavailable [[ STAT3 ]] inhibitor for cancer therapy."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 52,"In reference to ""The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists terfenadine, astemizole, loratadine, and [[ acrivastine ]] are reviewed."", what is the relation? antagonist In reference to ""Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]."", what is the relation? upregulator In reference to ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator In reference to ""The ability of << sulindac >> to block [[ ERK1/2 ]] signaling by the EGF receptor may account for at least part of its potent growth-inhibitory effects against cancer cells."", what is the relation? indirect-downregulator In reference to ""<< Uridine 5'-diphosphate- glucuronosyltransferases >> are colocalized with carboxylesterases and have the potential to further metabolize carboxylic acids to acyl glucuronides, but it is currently unknown if [[ acyl glucuronides ]], being esters, also interact with carboxylesterases."", what is the relation? product-of In reference to ""In relation to zinc bioavailability, α-CPPs, << β-CPPs >>, α(s1)-CN(64-74)4P and β-CN(1-25)4P increased [[ zinc ]] uptake."", what is the relation? substrate In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and [[ glutathioneperoxidase ]] (GPx) activities, while increased catalase (CAT) activity compared with the control."", what is the relation? downregulator In reference to ""Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist AM1241 [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole], the anandamide transport inhibitor [[ AM404 ]], and the CB antagonist rimonabant did not have diuretic effects."", what is the relation? agonist In reference to ""<< Cobalt chloride >>, a typical HIF activator, induced the gene expression of CAR-target genes, including cyp2b9 and [[ cyp2b10 ]], an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver."", what is the relation? indirect-upregulator In reference to ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", what is the relation? substrate_product-of In reference to ""The results suggest that the 63-kDa (PDE 1B1) and 60-kDa (PDE 1A2) << CaMPDE >> isozymes are inhibited by [[ felodipine ]] and nicardipine by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other."", what is the relation? inhibitor In reference to ""Thus, in 158N cells, the ability of << oxysterols >> to trigger a mode of cell death by apoptosis involving [[ GSK-3 ]] and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains."", what is the relation? activator In reference to ""The << x(c)- cystine transporter >> represents a novel target for sulfasalazine-like drugs with high potential for application in therapy of lymphoblastic and other malignancies dependent on extracellular [[ cyst(e)ine ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 53,"Regarding ""Several active analogues were also evaluated for their ability to block uptake of << DA >>, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-[[ hDAT ]], HEK-hSERT, and HEK-hNET cells."", can you determine the relation? substrate Regarding ""As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to metformin or pioglitazone and was noninferior to glipizide when added to [[ metformin ]]."", can you determine the relation? indirect-downregulator Regarding ""<< 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 ([[ TSC2 ]]) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2."", can you determine the relation? activator Regarding ""In the DRN, brexpiprazole completely inhibited the firing of 5-HT neurons via << 5-HT1A >> agonism and was more potent than [[ aripiprazole ]] (ED50 = 230 and 700 mug/kg, respectively)."", can you determine the relation? agonist Regarding ""Calmodulin was relatively ineffective in preventing inhibition of << cAMP phosphodiesterase >> by felodipine and the [[ p-chloro ]] analogue."", can you determine the relation? inhibitor Regarding ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", can you determine the relation? agonist-activator Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an [[ N-methyl d-aspartate receptor ]] (NMDAR) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting."", can you determine the relation? antagonist Regarding ""<< Statins >> increase p21 through inhibition of histone deacetylase activity and release of promoter-associated [[ HDAC1/2 ]]."", can you determine the relation? upregulator Regarding ""<< N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase >> (EC 3.1.4.45; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome."", can you determine the relation? product-of Regarding ""However, combined treatment with << cinobufagin >> and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-[[ PARP ]] in U2OS cells."", can you determine the relation? indirect-upregulator Regarding ""Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of [[ CA I ]] and CA II."", can you determine the relation? downregulator Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< AMCA >> (0.06 mM) and EACA (0.6 mM) were effective in prolonging clot lysis if (1) whole blood clots were formed and then exposed to a lysine analogue and exogenous t-PA or if (2) whole blood clots were formed in the presence of exogenous [[ t-PA ]] and a lysine analogue."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 54,"Regarding the sentence ""Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2."", what is the relation? downregulator Regarding the sentence ""Our results showed that low dose << BPA >> and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and [[ Nanog ]] proteins, while only BPA could downregulate the expression of E-cadherin protein."", what is the relation? indirect-upregulator Regarding the sentence ""Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists."", what is the relation? antagonist Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""The enzyme << cyclo-oxygenase >> catalyses the oxygenation of arachidonic acid, leading to the formation of [[ prostaglandins ]]."", what is the relation? product-of Regarding the sentence ""Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (<< 1400W >>), a selective inhibitor of iNOS, decreased the expression of E-selectin, [[ VEGF ]], and iNOS."", what is the relation? indirect-downregulator Regarding the sentence ""Several inhibitors of << Lp-PLA(2) >> have been described, including [[ darapladib ]], which is currently in phase 3 clinical development for the treatment of atherosclerosis."", what is the relation? inhibitor Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""In a cell-based model, << bleomycin >> suppressed Nrf2 activation via [[ extracellular signal-related kinase ]] phosphorylation, enhancing intracellular reactive oxygen species in lung fibroblasts and stimulating abnormal cell proliferation and collagen secretion."", what is the relation? activator Regarding the sentence ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and << activating protein-1 >>, which were increased in [[ fructose ]]-fed rats."", what is the relation? upregulator Regarding the sentence ""<< Zolmitriptan >> (Zomig; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura."", what is the relation? agonist Regarding the sentence ""Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, estrone 3-sulfate, and << dehydroepiandrosterone sulfate >> (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or [[ OATP1B3 ]]."", what is the relation? substrate Regarding the sentence ""Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited << DMN >>-induced increases in matrix metalloproteinase-13 ([[ MMP-13 ]]), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 55,"Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, << PPT-A >>) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells. what is the relation? indirect-upregulator BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific << alpha2-adrenoceptor >> agonists of the type such as [[ dexmedetomidine ]]. what is the relation? agonist Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). what is the relation? upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA). what is the relation? product-of The << 5-HT(2B/2C)-receptor >> antagonist [[ SB 206553 ]] facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect. what is the relation? antagonist High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates [[ tuberin ]] and activates mTOR. what is the relation? downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. what is the relation? substrate_product-of The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator Genistin decreased myosin light chain kinase (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of << MLCK >> contents and inhibition of MLCK activity are involved in the [[ genistin ]]-induced inhibitory effects. what is the relation? indirect-downregulator Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, [[ myeloperoxidase ]] activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05). what is the relation? inhibitor In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives (AA-861, [[ tBuBHQ ]], tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines. what is the relation? activator We found that reduction of the carcinogenic << hydroxylamines >> of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]. what is the relation? substrate TCDD or prochloraz doubled << ABCG2 >>-mediated [[ Hoechst H33342 ]] secretion. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 56,"Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities.""? agonist-activator Question: What is the relation in the sentence ""The 5-HT(1/2/5/7)-receptor antagonist methysergide and the << 5-HT(2A/2B/2C)-receptor >> antagonist [[ LY 53857 ]] enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it.""? antagonist Question: What is the relation in the sentence ""Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, [[ thymidine kinase-1 ]] and thymidylate synthase, in various types of cancer.""? product-of Question: What is the relation in the sentence ""On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]].""? upregulator Question: What is the relation in the sentence ""Even though the activities of << MAT >> and GNMT were elevated, the concentration of liver [[ S-adenosylmethionine ]] was decreased (24%, p<0.001) and S-adenosylhomocysteine increased (113%, p<0.001) in the dwarf mice.""? substrate Question: What is the relation in the sentence ""Expression of the dominant negative mutants arrestin-2(319-418) or dynamin I-K44A significantly reduced << U50,488H >>-induced down-regulation of the [[ hkor ]].""? downregulator Question: What is the relation in the sentence ""Moreover, << IGFBP-rP2 >> noticeably increased in response to TGF-beta1 and [[ all-trans retinoic acid ]] (atRA) in HPEC and PC-3 cells, and it decreased in response to IGF-I in HPEC.""? indirect-upregulator Question: What is the relation in the sentence ""Thus, it can be suggested that the inhibitory action of << ginseng saponins >> against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking norepinephrine- and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage rather than in the brain.""? indirect-downregulator Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""Recently, it has been shown that the activation of particular << T2R >> bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and [[ acesulfame-K ]].""? activator Question: What is the relation in the sentence ""The potent and selective third-generation << aromatase >> inhibitors anastrozole, [[ letrozole ]] and exemestane were introduced to the market as endocrine therapy in postmenopausal patients failing anti-estrogen therapy alone, or multiple hormonal therapies.""? inhibitor Question: What is the relation in the sentence ""Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist formoterol [[[ eformoterol ]]].""? agonist Question: What is the relation in the sentence ""<< GW660511X >> and omapatrilat increased the production of both BrBK1-8 and [[ Br-Phe5 ]] but not that of BrBK4-8 and BrBK2-8.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 57,"Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked << ABCA1 >>-mediated [[ cholesterol ]] efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM). Question: what is the relation? Answer: substrate << U50, 488H >> caused a significant down-regulation of the [[ hkor ]], although etorphine did not. Question: what is the relation? Answer: downregulator Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of << NO >> and the expression of inducible nitric-oxide synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes. Question: what is the relation? Answer: product-of << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Question: what is the relation? Answer: substrate_product-of Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, prazosin, [[ tamsulosin ]] and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials. Question: what is the relation? Answer: antagonist The values of mean corpuscular hemoglobin concentration and mean corpuscular << hemoglobin >> increased in the [[ STX ]] group. Question: what is the relation? Answer: indirect-upregulator Therefore, the objective of the present study was to investigate the effects of << PLA2 >> inhibitors p-bromophenacyl bromide (BPB) and [[ arachidonyl trifluoromethyl ketone ]] (AACOCF3) on interleukin-2 (IL-2) expression in murine primary splenocytes. Question: what is the relation? Answer: inhibitor Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of [[ PI3K ]]/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc. Question: what is the relation? Answer: indirect-downregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Question: what is the relation? Answer: agonist-activator Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells. Question: what is the relation? Answer: upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor The effects of the << adenosine A3 receptor >> agonist [[ IB-MECA ]] on sodium taurocholate-induced experimental acute pancreatitis. Question: what is the relation? Answer: agonist << Amprenavir >> efficiently activated [[ PXR ]] and induced PXR target gene expression in vitro and in vivo. Question: what is the relation? Answer: activator In overexpressing cell lines, OATP1B1- and OATP1B3-mediated estradiol-17β-glucuronide uptake and << OATP2B1 >>-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin [[ flavonolignans ]] investigated. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 58,"Regarding ""The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a ([[ SERCA2a ]]), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation."", can you determine the relation? substrate Regarding ""Second, C427A mutant human TOP2alpha, which exhibits reduced << ATPase >> activity, was shown to exhibit cross-resistance to all ATP-sensitive but not [[ ATP ]]-insensitive TOP2 poisons."", can you determine the relation? downregulator Regarding ""Finally, the amounts of << RORalpha >> and cAspAT mRNAs were similarly increased by [[ TZD ]] treatment of human adipose tissue explants, confirming coordinated regulation."", can you determine the relation? indirect-upregulator Regarding ""<< Bupropion >>, an efficacious antidepressant and smoking cessation agent, inhibits dopamine and norepinephrine transporters ([[ DAT ]] and NET, respectively)."", can you determine the relation? inhibitor Regarding ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", can you determine the relation? activator Regarding ""The << alpha(1)-adrenoceptor >> antagonist, [[ tamsulosin ]], is selective for alpha(1A)- and alpha(1D)- over alpha(1B)-adrenoceptors."", can you determine the relation? antagonist Regarding ""Aldose reductase (<< AR >>) catalyzes the reduction of toxic lipid aldehydes to their [[ alcohol ]] products and mediates inflammatory signals triggered by lipopolysaccharide (LPS)."", can you determine the relation? product-of Regarding ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", can you determine the relation? agonist-activator Regarding ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", can you determine the relation? upregulator Regarding ""Systemic administration of << beta2-adrenoceptor >> agonists, [[ formoterol ]] and salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses."", can you determine the relation? agonist Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""Separate << 5-aza-2'-deoxycytidine >> pretreatment or in combination with trichostatin A reduced (m)CpG and specific small interference RNAs targeting Mecp2 and [[ Creb1 ]] separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells."", can you determine the relation? indirect-downregulator Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""For some, pharmacologic inhibitors are available, including sorafenib for BRAF, farnesyltransferase inhibitors for NRAS, PD-0325901 for mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, << rapamycin >> analogues for [[ mammalian target of rapamycin ]], and agents that inhibit either vascular endothelial growth factor or its receptors."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 59,"Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist [[ formoterol ]] [eformoterol]."". Can you identify the relation? agonist Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""CONCLUSION: Oral << quinidine >> is effective in suppressing the gain of function in [[ IKr ]] responsible for some cases of short QT syndrome with a mutation in HERG and thus restoring normal rate dependence of the QT interval and rendering ventricular tachycardia/ventricular fibrillation noninducible."". Can you identify the relation? indirect-downregulator Consider the text ""Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration."". Can you identify the relation? upregulator Consider the text ""<< (125)I-Cyanopindolol >> saturation binding in Adv.beta(1) myocytes demonstrated approximately 18-fold increase in [[ beta(1)-adrenoceptors ]]."". Can you identify the relation? indirect-upregulator Consider the text ""Terfenadine and astemizole are chemically unrelated to << histamine H1-receptor >> antagonists such as [[ diphenhydramine ]] and chlorpheniramine."". Can you identify the relation? antagonist Consider the text ""Furthermore, << BRN-250 >> inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of [[ VEGF receptor 2 ]] (VEGFR2) and the activation of its downstream AKT pathway."". Can you identify the relation? inhibitor Consider the text ""BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA)."". Can you identify the relation? product-of Consider the text ""The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of [[ caspase-9 ]] and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways."". Can you identify the relation? activator Consider the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."". Can you identify the relation? agonist-activator Consider the text ""4-Hydroxynonenal (<< 4-HNE >>) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several glutathione S-transferase ([[ GST ]]) isoforms."". Can you identify the relation? substrate Consider the text ""To determine whether 3,4-methylenedioxymethamphetamine (<< MDMA >>)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured."". Can you identify the relation? downregulator Consider the text ""The << Intermediate-conductance Calcium-activated Potassium Channel KCa3.1 >> Regulates Vascular Smooth Muscle Cell Proliferation via Controlling [[ Calcium ]]-dependent Signaling."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 60,"In reference to ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of VEGFand MMP-9, resulting from the inhibition of [[ Akt ]] pathway."", what is the relation? inhibitor In reference to ""Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, << stem cell factor >> (SCF), and macrophage migration inhibitory factor (MIF)) were down-regulated by [[ artemisinic acid ]]."", what is the relation? indirect-downregulator In reference to ""In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with [[ rauwolscine ]], phentolamine, and idazoxan."", what is the relation? antagonist In reference to ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."", what is the relation? upregulator In reference to ""Leukotriene A(4) hydrolase (<< LTA(4)H >>) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to [[ LTB(4) ]]."", what is the relation? product-of In reference to ""Racemization of << serine >> is catalyzed by [[ serine racemase ]], a pyridoxal 5'-phosphate-dependent enzyme expressed mainly in brain and liver."", what is the relation? substrate In reference to ""Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced butein-induced HO-1 expression, and << butein >> treatment led to increased [[ JNK ]] phosphorylation."", what is the relation? activator In reference to ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""In hippocampal dentate gyrus, << MPH >>-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-[[ NCAM ]] (polysialylated form of neural cell adhesion molecule)."", what is the relation? indirect-upregulator In reference to ""OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha ([[ PPARalpha ]]) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent."", what is the relation? agonist In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""Expression of the dominant negative mutants rab5A-<< N133I >> or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation."", what is the relation? downregulator In reference to ""Rifampicin (10 micromol/L) inhibited << OATP8 >>-mediated [[ BSP ]] uptake by 50%, whereas inhibition of OATP-C-, OATP-B-, and OATP-A-mediated BSP transport was below 15%."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 61,"In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Please explain the relation. agonist-activator Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). Please explain the relation. upregulator Here, we demonstrate that << peptidyl-prolyl cis/trans-isomerase A1 >> (Pin1), an enzyme that catalyzes the conversion of the peptide bond of [[ pSer ]]/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification. Please explain the relation. substrate For << AII >> and ET1, MAP was also increased for the [[ fenofibrate ]] group but not in a dose-dependent fashion. Please explain the relation. indirect-upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor At 10(-6)M in transcription assays, none of these compounds showed progestin agonist activity, whereas << mifepristone >> and its monodemethylated metabolite manifested slight [[ glucocorticoid ]] agonist activity. Please explain the relation. agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of Upon activation by << phenobarbital >>, nuclear receptor [[ CAR ]] binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter. Please explain the relation. activator Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity. Please explain the relation. downregulator The most potent compound, << D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid >> (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini. Please explain the relation. antagonist However, whether increasing << EETs >> production by [[ CYP2J2 ]] overexpression in vivo could prevent abdominal aortic aneurysm (AAA) remains unknown. Please explain the relation. product-of << Rasagiline >> does not modify CNS monoamine tissue levels or monoamine-induced behavioural syndromes at doses which selectively inhibit MAO-B but not [[ MAO-A ]]. Please explain the relation. inhibitor In whole-cell voltage-clamp recordings from principal neurons of the rat basolateral amygdala, << topiramate >> at low concentrations (IC50, approximately 0.5 microm) selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by kainate receptors containing the [[ GluR5 ]] subunit. Please explain the relation. indirect-downregulator RESULT(S): The expression of endometrial ERalpha, PRAB, << PRB >>, and SRC-1 was increased significantly after 1 week of [[ mifepristone ]], but the increase was no longer seen after 10 weeks. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 62,"Regarding ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", can you determine the relation? agonist-activator Regarding ""While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of [[ H1-receptor ]] antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity."", can you determine the relation? agonist Regarding ""This study explored whether << curcumin >> improves colonic inflammation in a rat colitis model through inhibition of the TLR4/[[ NF-κB ]] signaling pathway and IL-27 expression."", can you determine the relation? inhibitor Regarding ""In combination with clofarabine, the ability of << resveratrol >> to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment."", can you determine the relation? downregulator Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""Thus, << SFO >> contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating [[ p75(NTR) ]] and IL-8 and cell apoptosis in plaque."", can you determine the relation? activator Regarding ""Luciferase reporter assays showed that transcription of << FDX1 >> was synergistically activated by the NR5A family and [[ 8Br-cAMP ]] treatment through two SF-1 binding sites and a CRE-like sequence in a human ovarian granulosa cell line, KGN."", can you determine the relation? indirect-upregulator Regarding ""Firstly, the V(max) of << GAD >> was increased when ApoCaM was present whereas the affinity for the substrate, [[ glutamate ]], was not affected."", can you determine the relation? substrate Regarding ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase ([[ CAT ]]) activity compared with the control."", can you determine the relation? upregulator Regarding ""In addition, << BGG >>-mediated inhibition of AR prevented LPS-induced activation of JNK and [[ p38 ]] and lowered ROS levels, which could inhibit LPS-induced apoptosis."", can you determine the relation? indirect-downregulator Regarding ""Prazosin (nonselective alpha(1)-adrenoceptor antagonist), << silodosin >> (selective [[ alpha(1A)-adrenoceptor ]] antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively)."", can you determine the relation? antagonist Regarding ""Cycloxygenase-2 (<< COX-2 >>)-derived prostaglandin E2 ([[ PGE2 ]]) has been shown to be important in esophageal tumorigenesis."", can you determine the relation? product-of Regarding ""The current study evaluates the effects of a selective << COX-2 >> inhibitor ([[ SC-236 ]]) on renal function in cirrhotic rats with ascites."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 63,"However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of [[ metallothionein-II ]] production, and an increase in p53 activation and the pro-apoptotic protein Bax. Please explain the relation. downregulator << Beta-1,4-galactosyltransferase I >> (beta4Gal-T1) normally transfers Gal from [[ UDP-Gal ]] to GlcNAc in the presence of Mn(2+) ion (Gal-T activity) and also transfers Glc from UDP-Glc to GlcNAc (Glc-T activity), albeit at only 0.3% efficiency. Please explain the relation. substrate The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific). Please explain the relation. agonist << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Please explain the relation. agonist-activator Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression and improved glucose tolerance parallel to [[ insulin ]] sensitivity in obese mice. Please explain the relation. indirect-upregulator Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. [[ alfuzosin ]], doxazosin, prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials. Please explain the relation. antagonist We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as [[ ascorbate peroxidase ]] (APX). Please explain the relation. product-of A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and << ellagic acid >>, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1). Please explain the relation. inhibitor Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512). Please explain the relation. upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor Docetaxel is a semisynthetic << taxane >> that inhibit tumor growth by induction of microtubule stabilization and promotion of [[ bcl-2 ]] inactivation, which induce apoptosis. Please explain the relation. indirect-downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h. Please explain the relation. activator The antidepressant << desipramine >> has been shown to decrease synaptic membrane concentrations of the norepinephrine re-uptake transporter ([[ NET ]]) in vivo and in vitro, on both an acute and a chronic basis. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 64,"<< Indomethacin >> activates carbonic anhydrase and antagonizes the effect of the specific [[ carbonic anhydrase ]] inhibitor acetazolamide, by a direct mechanism of action. Please explain the relation. activator Altogether, our findings support a model in which Top2β deficiency promotes << CPT >>-induced apoptosis in quiescent non-S-phase cells, possibly due to RNAP LS depletion and [[ p53 ]] accumulation. Please explain the relation. indirect-upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor There was no significant difference in TLR4, NF-κB, and << IL-27 >> mRNA and proteins between [[ curcumin ]]-treated and sulfasalazine-treated groups. Please explain the relation. indirect-downregulator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of Reactivators showed different activity in the reactivation of << rat brain AChE >> after [[ dichlorvos ]], paraoxon and tabun inhibition. Please explain the relation. inhibitor The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Please explain the relation. agonist-activator We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine << 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine >> (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]. Please explain the relation. substrate << Estrogens >> are biosynthesised from androgens by the [[ CYP450 ]] enzyme complex called aromatase. Please explain the relation. product-of Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced << NADPH oxidase >> activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by [[ resveratrol ]]. Please explain the relation. downregulator The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Please explain the relation. agonist Mutation of arginine 228 to << lysine >> enhances the [[ glucosyltransferase ]] activity of bovine beta-1,4-galactosyltransferase I. Please explain the relation. upregulator Since the original discovery of << azoles >> analogs as [[ PXR ]] antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic PXR antagonists. Please explain the relation. antagonist Western blot analysis of cells incubated with << imatinib >> demonstrated activation of [[ EGFR ]] and downstream signaling that was reduced by inhibition of mitogen-activated protein/extracellular signal-regulated kinase kinase 1 (MEK1) and EGFR, but not Her2/ErbB2. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 65,"In PFC, << DEX >> caused activation of [[ AKT ]], augmentation of pro-survival Bcl-2 protein and enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to mitochondria. Query: What is the relation? activator << Thalidomide >> reduced COX-2 expression accompanied by a decrease of [[ bcl-2 ]] protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60. Query: What is the relation? indirect-downregulator Histamine content, HDC activity and << HDC >> mRNA expression in nasal mucosa were also significantly increased after [[ TDI ]] provocation. Query: What is the relation? indirect-upregulator Enzyme kinetic analyses using human liver microsomes revealed inhibition of << CYP1A1 >> activity by delphinidin (IC50 78 μM) and [[ pelargonidin ]] (IC50 33 μM). Query: What is the relation? inhibitor Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Query: What is the relation? substrate_product-of The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased [[ superoxide dismutase ]] (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. Query: What is the relation? downregulator The non-selective << adenosine receptor >> antagonist ([[ caffeine ]]), and the selective adenosine A1 receptor antagonist (DPCPX), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice. Query: What is the relation? antagonist Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h. Query: What is the relation? upregulator Methionine synthase reductase (<< MTRR >>) is an enzyme involved in the conversion of Hcy to [[ methionine ]]. Query: What is the relation? product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Query: What is the relation? agonist-activator These findings demonstrate that << PEPT2 >> is the primary transporter responsible for [[ cefadroxil ]] uptake in the choroid plexus. Query: What is the relation? substrate Consistent with the weak transactivation activity of esterified-<< BM >> mediated by [[ rat GR ]], there were few side effects, evaluated by thymus involution and body weight loss, in an antigen-induced asthmatic model in rats. Query: What is the relation? agonist The ratio of TGF-beta1 absorbed light value to << GAPDH >> absorbed light value in the SHR group was 0.887+/-0.019, which was significantly higher than that in WKY group, [[ imidapril ]] group, and irbesartan group with the ratios of 0.780+/-0.018, 0.803+/-0.005, and 0.847+/-0.017, respectively (P<0.01). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 66,"G6PC2: A Negative Regulator of Basal << Glucose >>-Stimulated [[ Insulin ]] Secretion. what is the relation? upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. what is the relation? agonist-activator Discovery and optimization of << anthranilic acid sulfonamides >> as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of [[ albumin ]] binding. what is the relation? downregulator Together, this pharmacological profile of subtype-selective betaAR antagonists indicates that in this model, << beta1AR >> activation is responsible for the enhanced hippocampal CA3 network activity initiated by [[ isoproterenol ]]. what is the relation? agonist N-alkylation of the << pyridazinone >> ring markedly enhances potency against PDE4 but suppresses [[ PDE3 ]] inhibition. what is the relation? inhibitor Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor These results suggest that CYP2B6 genotype is the most important patient variable for predicting the level of << CYP2B6 >> activity in women, when measured by the metabolism of [[ bupropion ]]. what is the relation? substrate << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. what is the relation? substrate_product-of Tumor-growth-promoting << cyclooxygenase-2 >> [[ prostaglandin E2 ]] pathway provides medulloblastoma therapeutic targets. what is the relation? product-of Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h. what is the relation? indirect-upregulator << Ozone >> plus PM(2.5) exposure, however, induced CRP, IL-6, CK, LDH and MDA increase, [[ SOD ]] and HRV decrease significantly in a dose-response way. what is the relation? indirect-downregulator << [6]-Gingerol >> derived from Zingiber officinale Roscoe (ginger) was identified as a novel [[ angiotensin II type 1 receptor ]] antagonist, with an IC50 value of 8.173 µM. what is the relation? antagonist << Methylphenidate >> increased [[ DAT ]] Vmax in SHR mPFC and decreased DAT Vmax in WKY OFC. what is the relation? activator Furthermore, << galangin >> attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of [[ histamine receptor 1 ]] at the inflamed tissue. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 67,"RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. what is the relation? agonist-activator The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). what is the relation? agonist Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion><< gramine >>) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent. what is the relation? inhibitor For AII and << ET1 >>, MAP was also increased for the [[ fenofibrate ]] group but not in a dose-dependent fashion. what is the relation? indirect-upregulator Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats. what is the relation? upregulator Inhibition of endogenous production of << H(2)S >> by PAG significantly suppressed SP concentration, PPT-A expression and [[ NK1-R ]] expression in the acini. what is the relation? indirect-downregulator Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS). what is the relation? product-of Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]]. what is the relation? downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor In addition, << tolvaptan >> is metabolized by the [[ CYP3A4 ]] system; thus physicians should be aware of the potential for increased interactions with other medications. what is the relation? substrate The << CYP3A4 >> activity could be induced 2-fold by [[ rifampicin ]], whereas CYP2C9 activity remained equally high. what is the relation? activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). what is the relation? substrate_product-of The potency of the antipsychotic drug, << risperidone >>, to antagonize [[ alpha 1A-adrenoceptor ]]-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 1-adrenoceptor subtype-discriminating antagonists. what is the relation? antagonist The outflow of [3H]-MPP+ was significantly enhanced by MPP+, << guanidine >>, choline and amantadine as potential substrates for [[ OCT ]]-related transmembrane transporters. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 68,"Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, [[ prazosin ]], tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials. Please explain the relation. antagonist The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Please explain the relation. agonist-activator Favorable enzyme profiles (high TP and low << DPD >>) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS. Please explain the relation. product-of Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor We concluded that FDH has no direct role in the regulation of the above two pathways of Ser synthesis; the breakdown of << formate >> to CO(2) by the [[ FDH ]] reaction is the primary and preferred fate of the organic acid in Arabidopsis. Please explain the relation. substrate The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific). Please explain the relation. agonist Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of Phosphorylation of << AMPK >> at Thr172 increased by 1.4-fold within 5 min, and remained elevated throughout a 30-min time course, in response to [[ 2-deoxyglucose ]]. Please explain the relation. activator Taken together, these data demonstrated that << PLA2 >> inhibitors BPB and [[ AACOCF3 ]] are robust inhibitors of IL-2 expression at both the mRNA and protein levels in murine splenocytes. Please explain the relation. inhibitor << Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE ([[ RAGE ]]). Please explain the relation. indirect-downregulator Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms. Please explain the relation. downregulator << Orlistat >> treatment also results in modest improvements in total cholesterol, low-density lipoprotein, blood pressure, and fasting glucose and [[ insulin ]] concentrations. Please explain the relation. indirect-upregulator Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats. Please explain the relation. upregulator Furthermore, << gallium >> also seems to affect intracellular availability of iron already taken up via this pathway, probably due to its inhibitory activity on [[ vacuolar-type H(+)-ATPases ]]. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 69,"The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Question: what is the relation? Answer: agonist-activator The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, glutamate synthase, and [[ glutamate dehydrogenase ]], promoting amino acid conversion and protein synthesis in soybean seedlings. Question: what is the relation? Answer: downregulator EP(1) and << EP(3) receptor >> antagonists [[ ONO-8713 ]] and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth. Question: what is the relation? Answer: antagonist Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]]. Question: what is the relation? Answer: product-of Activating << glucocorticoid receptor >>-ERK signaling pathway contributes to [[ ginsenoside Rg1 ]] protection against β-amyloid peptide-induced human endothelial cells apoptosis. Question: what is the relation? Answer: activator In the reverse case, mutation of the orthologous glycine (Gly553) to methionine in carnitine octanoyltransferase (<< COT >>) decreased activity toward its natural substrates, medium- and long-chain acyl-CoAs, and increased activity toward short-chain [[ acyl-CoAs ]]. Question: what is the relation? Answer: substrate To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance. Question: what is the relation? Answer: upregulator << Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and [[ CK-MB ]], increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. Question: what is the relation? Answer: indirect-downregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition. Question: what is the relation? Answer: agonist In unstimulated cells, << Nor-NOHA >> dose-dependently reduced the [[ arginase ]] activity with maximal inhibition at 20 microM. Question: what is the relation? Answer: inhibitor << DNA methyltransferase 3a >> expression was increased in all [[ BPA ]] males and BPA 0.5 females and reduced in BPA 200 females. Question: what is the relation? Answer: indirect-upregulator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of Our findings reveal that << CdTe >>-QDs cause oxidative stress, interfere with antioxidant defenses and activate protein [[ kinases ]], leading to apoptosis via both extrinsic and intrinsic pathways. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 70,"The in vitro kinase activity of << PKC-alpha >> induced by I3A was lower than that induced by [[ PMA ]]. what is the relation? activator Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and [[ JNK1/2 ]] activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR. what is the relation? upregulator The beta-adrenergic/<< 5-HT1A >> receptor antagonist [[ (+/-)pindolol ]] and the selective 5-HT1B/D antagonist GR127935 produced no significant augmentation of venlafaxine-induced changes in either 5-HT or NA. what is the relation? antagonist The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of [[ nitrate reductase ]], glutamine synthetase, glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings. what is the relation? downregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. what is the relation? agonist-activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Kinetic parameters for << PAM >> inactivation by [[ 4-oxo-5-acetamido-6-phenyl-hex-2-enoic acid and 4-oxo-5-acetamido-6-(2-thienyl)-hex-2-enoic acid ]] were obtained by using both the conventional dilution assay method and the more complex progress curve method. what is the relation? inhibitor The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity. what is the relation? agonist Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released << glutamate >> and its conversion to glutamine through the enzyme [[ glutamine synthetase ]] (GS). what is the relation? substrate Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that << artemisinic acid >> regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the [[ hydroxymethylglutaryl CoA (HMG CoA) reductase ]] gene, which was mediated through reduced expression of the CCAAT/enhancer-binding protein (C/EBP) α gene. what is the relation? indirect-downregulator Adenylosuccinate synthetase (<< AdSS >>) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP. what is the relation? product-of One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of << PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as [[ p21 ]] and p27. what is the relation? indirect-upregulator SK-Br3 cells cultured in the presence of << topoisomerase IIalpha >> (TOP2A) inhibitors doxorubicin and [[ etopoxide ]] (VP-16) demonstrated a 2- to 3-fold increase in FAS promoter activity when compared with control cells growing in drug-free culture conditions. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 71,"Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", describe the relation. agonist-activator Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""<< Pranlukast >>, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from [[ leukotriene receptor ]] antagonism."", describe the relation. antagonist Given the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""The << M564G >> mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, [[ acetyl-CoA ]]."", describe the relation. substrate Given the text ""In study 1, cyclic ewes received vehicle, cortisol, << PF 915275 >> (PF; a selective inhibitor of [[ HSD11B1 ]]), cortisol and PF, meloxicam (a selective inhibitor of PTGS2), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus."", describe the relation. inhibitor Given the text ""In whole-cell voltage-clamp recordings from principal neurons of the rat basolateral amygdala, << topiramate >> at low concentrations (IC50, approximately 0.5 microm) selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by [[ kainate receptors ]] containing the GluR5 subunit."", describe the relation. indirect-downregulator Given the text ""The beneficial role of << 17beta-estradiol >> on blood pressure, cardiac hypertrophy, vascular [[ osteopontin ]] expression, perivascular fibrosis, and impaired NO-dependent relaxation of isolated aortic rings was completely abrogated by coadministration of medroxyprogesterone acetate."", describe the relation. indirect-upregulator Given the text ""Treatment with << diclofenac >> resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated [[ caspase-3 ]] after 6 hr, indicating that diclofenac may cause apoptosis of neuronal cells via activation of the caspase cascade."", describe the relation. activator Given the text ""On the other hand, in patients with a mean serum << carvedilol >> level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l."", describe the relation. downregulator Given the text ""Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."", describe the relation. upregulator Given the text ""<< 2-(2-Aminoethyl)-quinoline >> (D-1997): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", describe the relation. agonist Given the text ""The ultimate carcinogenic Phase I BP metabolite anti-BP-7,8-dihydrodiol-9,10-epoxide (BPDE) can be detoxified by << glutathione >> conjugate formation catalyzed by [[ glutathione S-transferases ]]."", describe the relation. product-of Given the text ""SK-Br3 cells cultured in the presence of topoisomerase IIalpha (<< TOP2A >>) inhibitors [[ doxorubicin ]] and etopoxide (VP-16) demonstrated a 2- to 3-fold increase in FAS promoter activity when compared with control cells growing in drug-free culture conditions."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 72,"Structure-activity relationship studies indicated that << 5-(p-toluenesulfonylamino)phthalimide >> moiety is a favorable scaffold to exert the [[ α-glucosidase ]] inhibitory activity and substituents at the N2 position have considerable influence on the efficacy of the inhibition activities. what is the relation? inhibitor Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, [[ thymidine kinase-1 ]] and thymidylate synthase, in various types of cancer. what is the relation? product-of Type I deiodinase, liver fatty-acid binding protein and << cytochrome P450 (CYP) 3A37 >> mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1. what is the relation? indirect-upregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms. what is the relation? downregulator << P2Y(2) receptor >> agonist [[ INS37217 ]] enhances functional recovery after detachment caused by subretinal injection in normal and rds mice. what is the relation? agonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. what is the relation? substrate_product-of The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives (AA-861, [[ tBuBHQ ]], tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines. what is the relation? activator Furthermore, << N >>-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase ([[ ERK ]]) and mTOR via suppression of Ras prenylation and enhanced Bim expression. what is the relation? indirect-downregulator In the rabbit pulmonary artery, rilmenidine and << oxymetazoline >> are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan. what is the relation? antagonist << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of [[ p21 ]](WAF1/CIP1) and p53. what is the relation? upregulator PIP5K1B encodes << phosphatidylinositol 4-phosphate 5-kinase β type I >> (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates [[ phosphatidylinositol 4-phosphate ]] [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. what is the relation? substrate In contrast, the << RA >> catabolising enzymes [[ Cyp26A1 ]] and Cyp26B1 which are known to be RA-responsive were not expressed at all in the developing eye. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 73,"In reference to ""Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (<< Pin1 >>), an enzyme that catalyzes the conversion of the peptide bond of pSer/pThr-[[ Pro ]] moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification."", what is the relation? substrate In reference to ""The IC50-values obtained for the inhibition of lipopolysaccharide (LPS)-induced release of prostaglandin E2 (PGE2) reflecting << cyclooxygenase (COX)-2 >>-mediated [[ PGE2 ]] release were 47 microg/ml and 0.6 microg/ml, for the Salix extract 1520L and rofecoxib-like research compound L745337, respectively."", what is the relation? product-of In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", what is the relation? substrate_product-of In reference to ""Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist AM1241 [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole], the anandamide transport inhibitor [[ AM404 ]], and the CB antagonist rimonabant did not have diuretic effects."", what is the relation? agonist In reference to ""siRNA knockdown of p38 MAPK abrogated the ability of << anisomycin >> to synergistically induce [[ CYP2B6 ]] mRNA."", what is the relation? indirect-upregulator In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator In reference to ""Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats."", what is the relation? upregulator In reference to ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of [[ R-spondins ]] (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD."", what is the relation? indirect-downregulator In reference to ""Activation of endogenous somatostatin receptor subtype 2 (<< sst2 >>) by [[ somatostatin-14 ]] or activation of transiently transfected rat D2 dopamine receptors (rD2(long)) by quinpirole had no effect."", what is the relation? activator In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, [[ cyclin E ]], cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator In reference to ""<< Mitiglinide >> (KAD-1229), a new anti-diabetic drug, is thought to stimulate insulin secretion by closing the [[ ATP-sensitive K+ (K(ATP)) channels ]] in pancreatic beta-cells."", what is the relation? inhibitor In reference to ""EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists ONO-AE3-208 and [[ AH 23848 ]], inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."", what is the relation? antagonist In reference to ""Moreover, << curcumin >> could also down-regulate the expression and activity of [[ matrix metalloproteinase-9 ]] (MMP-9)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 74,"Regarding ""<< Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of [[ cytochrome c ]] to the cytosol induced by DZN."", can you determine the relation? downregulator Regarding ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues."", can you determine the relation? product-of Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""Everolimus (<< RAD001 >>, Afinitor((R)) Novartis) is the first oral inhibitor of [[ mTOR ]] (mammalian target of rapamycin) to reach the oncology clinic."", can you determine the relation? inhibitor Regarding ""<< DBDCT >> also caused the phosphorylation of [[ JNK ]] and p38(MAPK)."", can you determine the relation? activator Regarding ""Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration."", can you determine the relation? upregulator Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""Additionally, << MPTP >> significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in Bax expression, cytochrome C translocation to the cytosol, andcleaved-[[ caspase-3 ]] expression, whereas these were inhibited by CRE or EB treatment."", can you determine the relation? indirect-upregulator Regarding ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the << adenosine A3 receptor >> agonist [[ IB-MECA ]] (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0.75 mg/kg b.w."", can you determine the relation? agonist Regarding ""Density functional theory calculations using the hybrid functional B3LYP have been performed to study the << methyl >> transfer step in [[ glycine N-methyltransferase ]] (GNMT)."", can you determine the relation? substrate Regarding ""A novel class of << quinoxalines >> has been discovered as antagonists of the [[ IgG ]]:FcRn protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen."", can you determine the relation? antagonist Regarding ""<< Curcumin >> improves TNBS-induced colitis in rats by inhibiting [[ IL-27 ]] expression via the TLR4/NF-κB signaling pathway."", can you determine the relation? indirect-downregulator Regarding ""As << thiamine >> metabolism deficiencies have been seen in placental infarcts previously, these indicate that PP20/[[ hTPK ]] may have a role in placental diseases."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 75,"<< ABT-199 >>, a potent and selective [[ BCL-2 ]] inhibitor, achieves antitumor activity while sparing platelets. Please explain the relation. inhibitor Taken together, our findings indicate that << 5HHMF >> suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent [[ HO-1 ]] activity. Please explain the relation. activator In contrast, the selective << beta2AR >> antagonists ICI-118,551 and butoxamine inhibited [[ isoproterenol ]]-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively). Please explain the relation. agonist Selective antagonism of GluR5 << kainate-receptor >>-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons. Please explain the relation. antagonist Moreover, protein and mRNA levels of DSS-induced proinflammatory << cytokines >> in colon, including TNF-α, IL-1β, IL-18, IL-17A and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]]. Please explain the relation. indirect-downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity. Please explain the relation. downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h. Please explain the relation. indirect-upregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator << Cholesterol >> uptake from [[ lipoproteins ]], intracellular vesicle transport and lipid transfer are also modified by oxysterols. Please explain the relation. substrate << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of [[ p21 ]](WAF1/CIP1) and p53. Please explain the relation. upregulator We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as [[ ascorbate peroxidase ]] (APX). Please explain the relation. product-of We demonstrate that two flavin mono-oxygenase family members, FMO1 and << FMO3 >>, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to [[ TMAO ]]. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 76,"Given the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", describe the relation. agonist-activator Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""In contrast to parenteral delivery of rBChE, which currently requires posttranslational modification for good plasma stability, an unmodified aer-rBChE pretreatment given 1-40h prior to >1 LD50 of aer-<< paraoxon >> (Px) was able to prevent inhibition of circulating [[ cholinesterase ]] in a dose-dependent manner."", describe the relation. activator Given the text ""Phospholipase A2 inhibitors << p-bromophenacyl bromide >> and arachidonyl trifluoromethyl ketone suppressed [[ interleukin-2 ]] (IL-2) expression in murine primary splenocytes."", describe the relation. indirect-downregulator Given the text ""<< N(5)-Substituted H(4)biopterin >> derivatives were not oxidized to products serving as substrates for [[ dihydropteridine reductase ]] and,depending on the substituent, were competitive inhibitors of phenylalanine hydroxylase: N(5)-methyl- and N(5)-hydroxymethyl H(4)biopterin inhibited phenylalanine hydroxylase, whereas N(5)-formyl- and N(5)-acetyl H(4)biopterin had no effect."", describe the relation. substrate Given the text ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase ([[ CAT ]]) activity compared with the control."", describe the relation. upregulator Given the text ""Previously, we have found that BRN-103, a << nicotinamide >> derivative, inhibits vascular endothelial growth factor ([[ VEGF ]])-mediated angiogenesis signaling in human endothelial cells."", describe the relation. inhibitor Given the text ""<< Amitriptyline >> is a [[ TrkA ]] and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity."", describe the relation. agonist Given the text ""The ratio between the GDC/<< SHMT >> and C1-THF synthase/SHMT pathways of [[ Ser ]] synthesis from [alpha-(13)C]Gly and [(13)C]formate, respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1."", describe the relation. product-of Given the text ""Previously, we showed that the << human kappa-opioid receptor >> (hkor) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged [[ U50,488H ]] treatment."", describe the relation. downregulator Given the text ""Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of << p21 >>(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2."", describe the relation. indirect-upregulator Given the text ""Derivatives of << 5-(dipentylamino)-5-oxo-pentanoic acid >> are a new class of non-peptide [[ cholecystokinin ]] (CCK) antagonists."", describe the relation. antagonist Given the text ""The expression of key genes important in << methionine >> metabolism, such as methionine adenosyltransferase-1a, [[ betaine-homocysteine methyltransferase ]] and thioether S-methyltransferase, were suppressed."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 77,"In reference to ""Sixteen of 34 CGPs inhibited << MRP1 >>-mediated [[ E217βG ]] uptake by >50% (IC50's 0.7-7.6 μM)."", what is the relation? substrate In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]."", what is the relation? upregulator In reference to ""In addition to << CYP2B6 >>, [[ anisomycin ]] co-treatment potentiated an increase in CYP2A7 and CYP2C9 mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs."", what is the relation? indirect-upregulator In reference to ""CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of [[ HDC ]] gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity."", what is the relation? product-of In reference to ""In another experiment, << cyanopindolol >>, an antagonist of the [[ serotonin terminal autoreceptor ]], also prolonged the clearance of 5-HT from the CA3 region."", what is the relation? antagonist In reference to ""The results of this study suggest that << noradrenaline >> predominantly, but not exclusively, mediates contraction of rat aorta through the activation of an [[ alphalD-adrenoceptor ]]."", what is the relation? activator In reference to ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in << MSG >>-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased [[ pIR ]] by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", what is the relation? downregulator In reference to ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific)."", what is the relation? agonist In reference to ""<< Licofelone >> reduced intima/media ratio in injured arteries, the macrophages infiltration in the neointimal area, [[ monocyte chemoattractant protein-1 ]] (MCP-1) gene expression, and the activation of nuclear factor-kappaB in rabbit atheroma."", what is the relation? indirect-downregulator In reference to ""Effects of felodipine (a << dihydropyridine >> [[ calcium channel ]] blocker) and analogues on calmodulin-dependent enzymes."", what is the relation? inhibitor In reference to ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""<< Nicotinamide N-methyltransferase >> (NNMT) catalyses the conversion of [[ nicotinamide ]] to 1-methylnicotinamide and plays an important role in hepatic detoxification reactions."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 78,"Consider the text ""Purified PAOh1/<< SMO >> oxidizes both [[ spermine ]] (K(m)=1.6 microM) and N(1)-acetylspermine (K(m)=51 microM), but does not oxidize spermidine."". Can you identify the relation? substrate Consider the text ""Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats."". Can you identify the relation? upregulator Consider the text ""Sorafenib (<< BAY 43-9006 >>, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and [[ tyrosine kinases ]] VEGFR/PDGFR in tumor vasculature."". Can you identify the relation? inhibitor Consider the text ""The sympathetic nerves of both the human atrial appendages and rabbit pulmonary artery are endowed with << alpha(2A)-autoreceptors >>, at which, however, both rilmenidine and [[ oxymetazoline ]] exhibit different properties (antagonism and agonism, respectively)."". Can you identify the relation? agonist Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""METHODS: << Cyclooxygenase >> activity and selectivity was determined in vitro by measuring [[ prostaglandin E(2) ]] (PGE(2)) production following incubation of varying concentrations of NSAID with human recombinant COX-1 or COX-2 and arachidonic acid."". Can you identify the relation? product-of Consider the text ""<< DBDCT >> also caused the phosphorylation of JNK and [[ p38 ]](MAPK)."". Can you identify the relation? activator Consider the text ""The effect of sumatriptan, but not of LY 344864, was prevented by pretreatment with the antagonist << SDZ 21-009 >>, which displays high affinity for [[ rat 5-HT1B ]] receptors."". Can you identify the relation? antagonist Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""To determine whether 3,4-methylenedioxymethamphetamine (<< MDMA >>)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured."". Can you identify the relation? downregulator Consider the text ""Furthermore, treatment with << spironoclactone >> not only attenuated the pro-apoptotic effect of ALD but reversed the ALD-induced increase of [[ calpain ]] and AIF levels."". Can you identify the relation? indirect-downregulator Consider the text ""<< Ozone >> plus PM(2.5) exposure, however, induced [[ CRP ]], IL-6, CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way."". Can you identify the relation? indirect-upregulator Consider the text ""Using hNET in transfected human embryonic kidney-293 cells, this difference in potency for DVS at sites labeled by [(3)H]NIS was found to distinguish DVS, the DVS analog rac-(1-[1-(3-chloro-phenyl)-2-(4-methylpiperazin-1-yl)-ethyl]cyclohexanol (WY-46824), methylphenidate, and the cocaine analog 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester (RTI-55) from other << hNET >> antagonists, such as NIS, mazindol, tricyclic antidepressants, and [[ cocaine ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 79,"Regarding the sentence ""In vivo << lorglumide >> antagonizes the contraction of the gall bladder of the guinea pig and of the dog provoked by i.v. [[ CCK-8 ]] or ceruletide (caerulein)."", what is the relation? antagonist Regarding the sentence ""<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted ([[ DeltaKPQ ]]) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings."", what is the relation? downregulator Regarding the sentence ""Our results have shown that << MMP-9 >> messenger ribonucleic acid (mRNA) expression was inhibited by [[ doxycycline ]] starting at 10 mg/kg/day (P<0.02)."", what is the relation? indirect-downregulator Regarding the sentence ""In breast cancer, intratumoural << aromatase >> is the source for local [[ estrogen ]] production in the tissue."", what is the relation? product-of Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""Monocarboxylate transporters (<< MCTs >>) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, [[ pyruvate ]], as well as ketone bodies."", what is the relation? substrate Regarding the sentence ""New classes of << pyrrole >>-derived nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as [[ COX-2 ]] selective inhibitors and NO donors were synthesized and are herein reported."", what is the relation? inhibitor Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity."", what is the relation? upregulator Regarding the sentence ""In the DRN, brexpiprazole completely inhibited the firing of 5-HT neurons via << 5-HT1A >> agonism and was more potent than [[ aripiprazole ]] (ED50 = 230 and 700 mug/kg, respectively)."", what is the relation? agonist Regarding the sentence ""However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of metallothionein-II production, and an increase in p53 activation and the pro-apoptotic protein [[ Bax ]]."", what is the relation? indirect-upregulator Regarding the sentence ""Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced butein-induced HO-1 expression, and << butein >> treatment led to increased [[ JNK ]] phosphorylation."", what is the relation? activator Regarding the sentence ""The results show that transient arsenite pre-treatment induces Hsp72, HO-1 and, to a lesser extent, Hsp27; it reduces H2O2-induced astrocyte death; and it causes selective activation of << Akt >> following [[ H2O2 ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 80,"In reference to ""Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in [[ ERK1/2 ]] and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR."", what is the relation? upregulator In reference to ""One of the mechanism of << mifepristone >> action on decreasing leiomyomata volume may be related to suppression on expression of [[ PR gene ]]."", what is the relation? indirect-downregulator In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible << nitric-oxide >> synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes."", what is the relation? product-of In reference to ""No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary efflux transporters [[ BSEP ]] and MRP2 or mitochondrial toxicity to THLE or HepG2 cells."", what is the relation? inhibitor In reference to ""Although generally highly specific for angiotensin II type 1 receptors, some ARBs, particularly << telmisartan >>, are partial agonists at [[ peroxisome proliferator-activated receptor-γ ]]."", what is the relation? agonist In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2."", what is the relation? downregulator In reference to ""Cholesterol esterase (<< CE >>) induced surface erosion of [[ poly(ethylene carbonate) ]] (PEC) and drug release from PEC under mild physiological environment was investigated."", what is the relation? substrate In reference to ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator In reference to ""Ca(v)1.3 channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to dihydropyridine (<< DHP >>) [[ L-VGCC ]] antagonists."", what is the relation? antagonist In reference to ""<< Cobalt chloride >>, a typical HIF activator, induced the gene expression of CAR-target genes, including cyp2b9 and [[ cyp2b10 ]], an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver."", what is the relation? indirect-upregulator In reference to ""<< cAspAT >> activity, as well as the incorporation of [(14)C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was stimulated by the thiazolidinedione (TZD) [[ rosiglitazone ]]."", what is the relation? activator In reference to ""The present results suggest that the action of << DMI >> in this animal model is unlikely to be directly related to a reduction in [[ beta-adrenoceptors ]] but may be related to a reduction in frontal cortical 5-HT2A receptors."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 81,"Question: What is the relation in the sentence ""Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.""? product-of Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity.""? agonist-activator Question: What is the relation in the sentence ""<< Conivaptan >> is a nonpeptide dual [[ V1a/V2 AVP receptor ]] antagonist.""? antagonist Question: What is the relation in the sentence ""Under isotonic conditions, << N-ethylmaleimide >> (NEM) produced [[ KCC ]] activation and transient cell shrinkage.""? activator Question: What is the relation in the sentence ""In this study, we demonstrate significant inhibitory activity of << dasatinib >> against both wild-type [[ KIT ]] and the KITD816V mutation in the nanomolar range in in vitro and cell-based kinase assays.""? inhibitor Question: What is the relation in the sentence ""Transport by OATP1B1 and << OATP1B3 >> enhances the cytotoxicity of [[ epigallocatechin 3-O-gallate ]] and several quercetin derivatives.""? substrate Question: What is the relation in the sentence ""The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity.""? agonist Question: What is the relation in the sentence ""CONCLUSION: A long-term intake of ethanol solution down-regulates the phosphorylation of << CREB >> in the nucleus accumbens, and those changes can be reversed by [[ naloxone ]], which may be one kind of the molecular mechanisms associated with ethanol dependence.""? upregulator Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and [[ IL-27 ]] p28 protein (p < 0.05).""? indirect-downregulator Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, [[ c-Myc ]], and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.""? downregulator Question: What is the relation in the sentence ""The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and [[ Aβ1-42 ]] in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of amyloid precursor protein (APP).""? indirect-upregulator Question: What is the relation in the sentence ""We have analyzed binding domains of the oxytocin receptor for barusiban, a highly selective oxytocin receptor antagonist, in comparison to the combined << vasopressin V1A/oxytocin receptor >> antagonist [[ atosiban ]] and the agonists oxytocin and carbetocin.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 82,"Regarding the sentence ""In membranes from HEK293 cells transfected with << alpha2-receptors >>, etomidate inhibited binding of the alpha2-antagonist, [[ [3H]RX821002 ]], with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm)."", what is the relation? antagonist Regarding the sentence ""One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, << EC 2.1.2.1 >>) with [[ glycine ]] (Gly) as one-carbon (1-C) source."", what is the relation? substrate Regarding the sentence ""Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats."", what is the relation? downregulator Regarding the sentence ""Neonatal << quinpirole >> treatment produced a significant decrease in [[ BDNF ]] and ChAT in the frontal cortex that was unaffected by olanzapine treatment."", what is the relation? indirect-downregulator Regarding the sentence ""<< Indomethacin >> treatment led to an increase in lipid peroxidation, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities and to a decrease in [[ catalase ]] activity and glutathione levels in gastric mucosa."", what is the relation? inhibitor Regarding the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme."", what is the relation? upregulator Regarding the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator Regarding the sentence ""The << CYP3A4 >> activity could be induced 2-fold by [[ rifampicin ]], whereas CYP2C9 activity remained equally high."", what is the relation? activator Regarding the sentence ""The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure."", what is the relation? agonist Regarding the sentence ""These unexpected and intriguing complexities seem likely to have some as yet undefined role in regulating << SSAT >> activity or stability as a part of [[ polyamine ]] homeostasis."", what is the relation? product-of Regarding the sentence ""Ginsenosides Rb2, Rd and Rg1 significantly decreased << norepinephrine >> and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage cell line (RAW 264.7)."", what is the relation? indirect-upregulator Regarding the sentence ""In contrast, << EGCG >> markedly downregulated major bile acid transporters ([[ Asbt ]] and Ostα) and regulatory molecules (Shp and Fgf15) in the ileum."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 83,"Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/<< Bcl2 >> ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]. Please explain the relation. downregulator << KCNK1 >>, a member of the family of two-pore K(+) ion channels, is specifically induced in the livers of male mice after [[ phenobarbital ]] treatment. Please explain the relation. activator << Amitriptyline >> is a [[ TrkA ]] and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Please explain the relation. agonist The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of [[ AchE ]] activity, CRP, NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level. Please explain the relation. upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of << Ifenprodil >>, known as the [[ GluNR2B ]] antagonist of reference, was chosen as the template for the elaboration of probes. Please explain the relation. antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor The << mitochondrial respiratory chain complex IV >> (cytochrome c oxidase) is a multi-subunit enzyme that transfers electrons from cytochrome c to molecular [[ oxygen ]], yielding water. Please explain the relation. substrate Cotreatment with U0126 and << YC-1 >> synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, JNK, and [[ beta-catenin ]]. Please explain the relation. indirect-downregulator Moreover, << IGFBP-rP2 >> noticeably increased in response to TGF-beta1 and all-trans retinoic acid ([[ atRA ]]) in HPEC and PC-3 cells, and it decreased in response to IGF-I in HPEC. Please explain the relation. indirect-upregulator The inhibitory effect of PGE1 or sulprostone was prevented by pretreatment with pertussis toxin [islet activating protein (IAP)] or phorbol-12-myristate-13-acetate (PMA), and the protein kinase C (<< PKC >>) inhibitor [[ chelerythrine ]] blocked the action of PMA. Please explain the relation. inhibitor RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Please explain the relation. agonist-activator Prednisolone also inhibited ACTH and << cortisol >> secretion in response to exogenous [[ CRH ]] stimulation, inferring rapid feedback inhibition at the anterior pituitary. Please explain the relation. product-of Fenofibrate and << GW2331 >> induced expression of acyl-coenzyme A (CoA) oxidase and enoyl-CoA hydratase and reduced [[ apolipoprotein C-III ]] and phosphoenolpyruvate carboxykinase mRNAs. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 84,"In reference to ""The studies with dThyd rescue from << cyclin E >>-cdk2 protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance."", what is the relation? indirect-upregulator In reference to ""Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues."", what is the relation? product-of In reference to ""The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the [[ Ras ]]/MEK/ERK and Ras/mTOR pathways."", what is the relation? inhibitor In reference to ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized << KCNK1 >> as a [[ phenobarbital ]]-inducible antihyperplasia factor."", what is the relation? activator In reference to ""The << mitochondrial respiratory chain complex IV >> (cytochrome c oxidase) is a multi-subunit enzyme that transfers electrons from cytochrome c to molecular [[ oxygen ]], yielding water."", what is the relation? substrate In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction."", what is the relation? antagonist In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator In reference to ""Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2."", what is the relation? downregulator In reference to ""In healthy rats, << ATB-429 >> dose dependently (25, 50, or 100 mg/kg) attenuated CRD-induced hypersensitivity and significantly inhibited CRD-induced overexpression of spinal [[ c-FOS ]] mRNA, whereas mesalamine had no effect."", what is the relation? indirect-downregulator In reference to ""Pre-clinical pharmacology of zolmitriptan (<< Zomig >>; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine."", what is the relation? agonist In reference to ""Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line."", what is the relation? upregulator In reference to ""Physiologic levels of << Mg(2+) >> ions decrease [[ ALDH1 ]] activity in part by increasing NADH binding affinity to the enzyme."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 85,"Consider the text ""Despite the importance of << AKRs >> in [[ PAHs ]] metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs)."". Can you identify the relation? substrate Consider the text ""Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible << nitric-oxide >> synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes."". Can you identify the relation? product-of Consider the text ""Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB [[ p65 ]] protein, and IL-27 p28 protein (p < 0.05)."". Can you identify the relation? indirect-downregulator Consider the text ""Treatment with << carvedilol >> reversed both protein and mRNA of HIF-1alpha, VEGF, BNP, and [[ NGF-beta ]] to the baseline values."". Can you identify the relation? indirect-upregulator Consider the text ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats."". Can you identify the relation? upregulator Consider the text ""Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, [[ doxazosin ]], prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials."". Can you identify the relation? antagonist Consider the text ""The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition."". Can you identify the relation? agonist Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, [[ DNMT-3a ]], and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."". Can you identify the relation? downregulator Consider the text ""It is concluded that << D-1997 >> contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the [[ 5-HT1A ]] or 5-HT1B receptor subtypes."". Can you identify the relation? activator Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."". Can you identify the relation? agonist-activator Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""<< Ca(v)1.3 >> channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to dihydropyridine ([[ DHP ]]) L-VGCC antagonists."". Can you identify the relation? inhibitor Consider the text ""In this work a novel approach combining HPLC-UV on-line with oaTOF-MS and ICPMS was applied to investigate in human and rat plasma the metabolism of labelled BK (79/81 Br-Phe5) BrBK in the presence of two new dual << ACE >>/NEP inhibitors ([[ GW660511X ]] and omapatrilat) currently under clinical trial."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 86,"<< Pranlukast >>, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from [[ leukotriene receptor ]] antagonism. Question: what is the relation? Answer: antagonist << N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase >> (EC 3.1.4.45; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome. Question: what is the relation? Answer: product-of Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and << sulprostone >> (an [[ EP3 ]]-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. Question: what is the relation? Answer: agonist << Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/[[ Bcl2 ]] ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. Question: what is the relation? Answer: indirect-downregulator << DBDCT >> up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of [[ Bax ]]/Bcl-2. Question: what is the relation? Answer: indirect-upregulator In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins ([[ MeCP-2 ]], MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Question: what is the relation? Answer: downregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor PURPOSE: Dasatinib (<< BMS-354825 >>), a potent oral multi-targeted kinase inhibitor against SRC and [[ BCR ]]-ABL, has recently been approved for the treatment of chronic myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance. Question: what is the relation? Answer: inhibitor The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Question: what is the relation? Answer: agonist-activator Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512). Question: what is the relation? Answer: upregulator Cross-inhibition of << SR-BI >>- and ABCA1-mediated [[ cholesterol ]] transport by the small molecules BLT-4 and glyburide. Question: what is the relation? Answer: substrate Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively. Question: what is the relation? Answer: activator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of We find that FP causes a decrease in stimulated eosinophil secretion of << LTC4 >> that is regulated by phospholipase A2 ([[ PLA2 ]]). Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 87,"Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."", what is the relation? upregulator Regarding the sentence ""It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and [[ BRCA2 ]] mutations, although preliminary evidence favors benefit for at least those with a BRCA2 mutation."", what is the relation? downregulator Regarding the sentence ""RORalpha ectopic expression activated the << cAspAT >> gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by [[ rosiglitazone ]] treatment of adipocytes."", what is the relation? indirect-upregulator Regarding the sentence ""This inhibition was blocked when mice were pretreated with the selective << H3R >> agonist [[ R-(alpha)-methyl-histamine ]] (10 mg/kg)."", what is the relation? agonist Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""Aldose reductase (<< AR >>) catalyzes the reduction of toxic lipid [[ aldehydes ]] to their alcohol products and mediates inflammatory signals triggered by lipopolysaccharide (LPS)."", what is the relation? substrate Regarding the sentence ""In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and [[ ATF-2 ]], together with the expression of HSP70 and Bax proteins."", what is the relation? activator Regarding the sentence ""<< Catecholamines >> (adrenaline, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, [[ EC 1.14.16.1 ]])."", what is the relation? inhibitor Regarding the sentence ""In the rabbit pulmonary artery, << rilmenidine >> and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan."", what is the relation? antagonist Regarding the sentence ""This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of << TCDD >> on canonical [[ Wnt ]] signaling and prostatic bud formation."", what is the relation? indirect-downregulator Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and << cortisol >> via [[ hydroxysteroid (11-β) dehydrogenase 1 ]] (HSD11B1)."", what is the relation? product-of Regarding the sentence ""In addition, the << factor Xa >> inhibitor [[ apixaban ]] is in late-stage clinical development."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 88,"Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist salbutamol 8 mg ([[ SAL ]]), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors. Query: What is the relation? agonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor Next, we examined the role of Rho family GTPases in the << ceramide >>-induced signalling to [[ SRE ]] activation. Query: What is the relation? activator The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of << navitoclax >>, a selective inhibitor of both [[ BCL-2 ]] and BCL-2-like 1 (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. Query: What is the relation? inhibitor << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), [[ CDK4 ]], c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Query: What is the relation? downregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. Query: What is the relation? upregulator << UGT1A6 >> exhibited a significantly higher Vmax and Km values toward both HFC and UDP-[[ glucuronic acid ]] than the other UGTs. Query: What is the relation? substrate One of the enzymes responsible for the production of << KA >>, [[ kynurenine aminotransferase I ]] (KATI), also catalyses the reversible transamination of glutamine to oxoglutaramic acid (GTK, EC 2.6.1.15). Query: What is the relation? product-of Alprenolol and << BAAM >> also caused surmountable antagonism of isoprenaline responses, and this [[ beta 1-adrenoceptor ]] antagonism was slowly reversible. Query: What is the relation? antagonist In conclusion, the production of IL-4 and << IL-5 >> by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by [[ DEX ]] than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma. Query: What is the relation? indirect-downregulator The reduction of << P2X3 >> expression levels was reversed by the proteasomal inhibitor [[ MG-132 ]]. Query: What is the relation? indirect-upregulator Agonist and antagonist actions of yohimbine as compared to << fluparoxan >> at [[ alpha(2)-adrenergic receptors ]] (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 89,"It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced [[ NF-κB ]] activation that involves degradation of I-κBε and nuclear translocation of c-Rel/p50 in alveolar epithelial cells. what is the relation? inhibitor Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of AchE activity, [[ CRP ]], NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level. what is the relation? indirect-upregulator Activation of << ALDH2 >> with [[ ethanol ]] attenuates diabetes induced myocardial injury in rats. what is the relation? activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of Concentration-dependent inhibitory effects of baicalin on the metabolism of << dextromethorphan >>, a dual probe of [[ CYP2D ]] and CYP3A, in rats. what is the relation? substrate Conversely, AMPK inhibitor compound C or GSK3β inhibitor << SB216763 >> blocked the cleavages of PARP and [[ caspase 3 ]] induced by ursolic acid in HepG2 cells. what is the relation? indirect-downregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. what is the relation? agonist-activator The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals. what is the relation? antagonist << L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or [[ 2-oxobutyrate ]]. what is the relation? product-of Second, C427A mutant human TOP2alpha, which exhibits reduced << ATPase >> activity, was shown to exhibit cross-resistance to all ATP-sensitive but not [[ ATP ]]-insensitive TOP2 poisons. what is the relation? downregulator << All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]]. what is the relation? upregulator OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a [[ peroxisome proliferator-activated receptor alpha ]] (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent. what is the relation? agonist It is thought to play a critical role in the visual cycle by functioning as an acceptor of << 11-cis-retinol >> from the [[ isomerohydrolase ]] reaction. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 90,"Consider the text ""These observations suggest that uptake of << phenformin >> into liver mitochondria is at least partly mediated by [[ OCTN1 ]] and functionally relevant to its inhibition potential of complex I respiration."". Can you identify the relation? substrate Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Suppression of << Src >>/ERK and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells."". Can you identify the relation? downregulator Consider the text ""Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized << KCNK1 >> as a [[ phenobarbital ]]-inducible antihyperplasia factor."". Can you identify the relation? activator Consider the text ""Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (<< M/TPO-Ag >>) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis."". Can you identify the relation? upregulator Consider the text ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."". Can you identify the relation? agonist-activator Consider the text ""<< GPxs >> reduce hydroperoxides to the corresponding [[ alcohols ]] by means of glutathione (GSH)."". Can you identify the relation? product-of Consider the text ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]]."". Can you identify the relation? indirect-downregulator Consider the text ""Brexpiprazole reversed the inhibitory effect of the DA agonist << apomorphine >> on VTA DA neurons (ED50 = 61 mug/kg), whereas it was ineffective when administered alone, indicating partial agonistic action on [[ D2 receptors ]]."". Can you identify the relation? agonist Consider the text ""Inhibition of binding of the << alpha2-receptor >> antagonist [[ [3H]RX821002 ]] to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro."". Can you identify the relation? antagonist Consider the text ""Taken together, these data demonstrate that << baicalin >> inhibits the metabolism of DXM in a concentration-dependent manner in rats, possibly through inhibiting hepatic CYP2D and [[ CYP3A ]] activities."". Can you identify the relation? inhibitor Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Moreover, << IGFBP-rP2 >> noticeably increased in response to TGF-beta1 and [[ all-trans retinoic acid ]] (atRA) in HPEC and PC-3 cells, and it decreased in response to IGF-I in HPEC."". Can you identify the relation? indirect-upregulator Consider the text ""Results confirmed that << YR-11 >> peptide inhibited pro-inflammatory cytokines in the sera and hind paw tissues of AIA rats through its suppressive effect on RANKL induced nuclear translocation of [[ NF-κB ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 91,"Neonatal << quinpirole >> treatment produced a significant decrease in BDNF and [[ ChAT ]] in the frontal cortex that was unaffected by olanzapine treatment. what is the relation? indirect-downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor << All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]]. what is the relation? upregulator Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II. what is the relation? product-of The mouse << CYP2J >> subfamily includes members that have wide tissue distribution and are active in the metabolism of [[ arachidonic acid ]] (AA), linoleic acid (LA), and other lipids and xenobiotics. what is the relation? substrate One of the << CB2 >> agonists, [[ N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1,3,5-triazin-2-amine ]] (19, -logEC(50)=7.5, E(max)=255%) was selected for further development. what is the relation? agonist One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). what is the relation? substrate_product-of Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of << p21 >>(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2. what is the relation? indirect-upregulator Only pMPPI [<< 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride >>], a selective [[ 5-HT(1A) ]] antagonist, was effective in inhibiting all 5-HT syndrome behaviors produced by lisuride, whereas pMPPI was without effect on any behavior induced by LSD. what is the relation? antagonist The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. what is the relation? agonist-activator << Licofelone >>, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and cyclooxygenase ([[ COX ]]) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability. what is the relation? inhibitor The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase ([[ SOD ]]) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. what is the relation? downregulator Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers ([[ sulforaphane ]], tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments. what is the relation? activator The time course of << PGE2 >> production was consistent with early release due to COX-1 activity followed by increased production 2-3 hours after surgery, consistent with [[ COX-2 ]] expression. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 92,"Ferredoxin 1 (<< FDX1 >>; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues. Query: What is the relation? product-of These results suggest that PDE4B mediates the antipsychotic effects of rolipram in CAR and that the << PDE4B >>-regulated [[ cyclic adenosine monophosphate ]] signaling pathway may play a role in the pathophysiology and pharmacotherapy of psychosis. Query: What is the relation? substrate Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats. Query: What is the relation? upregulator Galanin attenuates << cyclic AMP regulatory element-binding protein >> (CREB) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures. Query: What is the relation? activator OBJECTIVES: The alkaloid galantamine (<< GAL >>), which exhibits a combined [[ anticholinesterase ]] and direct parasympathomimetic mechanism of action, is employed in conjunction with therapeutic interventions in the stimulation of central cholinergic transfer in cognitive diseases. Query: What is the relation? inhibitor The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the << 5-HT1A >> receptor antagonist [[ spiroxatrine ]] (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM). Query: What is the relation? antagonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor Levels of << Cx43 >> protein were also decreased in a dose- and time-dependent manner following [[ antofine ]] treatment. Query: What is the relation? indirect-downregulator The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Query: What is the relation? agonist-activator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Suppression of Src/ERK and << GSK-3 >>/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells. Query: What is the relation? downregulator Furthermore, compared with control groups, the plaque endothelium level of << p75(NTR) >> was 3-fold increased and the liver level of p75(NTR) was 17.4-fold increased by [[ SFO ]]-HD. Query: What is the relation? indirect-upregulator The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α ([[ TNF- α ]]). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 93,"Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Prolonged use of << tolvaptan >> leads to increased endogenous levels of [[ AVP ]] and perhaps over-stimulation of V(1A) receptors. Please explain the relation. indirect-upregulator This study examined the inward transport of << l-[(14)C]alanine >>, an [[ ASCT2 ]] preferential substrate, in monolayers of immortalized renal proximal tubular epithelial (PTE) cells from Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Please explain the relation. substrate << Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, [[ amines ]], and thiols, respectively. Please explain the relation. product-of Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen ([[ PSA ]]) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT). Please explain the relation. indirect-downregulator Liver << BHMT >> activity was 1.3-fold higher in rats fed the Met deficient diet containing [[ choline ]], which was reflected in corresponding increases in mRNA content and immunodetectable protein. Please explain the relation. activator << Conivaptan >>: a dual [[ vasopressin receptor v1a/v2 ]] antagonist [corrected]. Please explain the relation. antagonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Please explain the relation. substrate_product-of In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator Moreover, kinetic analysis revealed that inhibition by << reserpine >>, a typical [[ VMAT2 ]] inhibitor, was uncompetitive, decreasing maximum velocity and affinity for dopamine. Please explain the relation. inhibitor This observation suggests that << MDMA >>-induced reductions in [[ SERT ]] density do not represent neuroadaptive responses to decreased levels of brain serotonin, but may occur in response to some other stimulus or to the neurotoxic effects of MDMA. Please explain the relation. downregulator Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an [[ EP1 ]]-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. Please explain the relation. agonist Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Please explain the relation. upregulator Gossypol and its isomers were non-competitive inhibitors of human and hamster LDH-X with respect to the coenzyme NADH, competitive inhibitors of human LDH-X and noncompetitive-competitive inhibitors of << hamster LDH-X >> with respect to the substrate [[ alpha-ketobutyrate ]]. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 94,"Question: What is the relation in the sentence ""In contrast, the << D-1997 >>-induced responses were potently and concentration-dependently antagonized by the mixed [[ 5-HT1-like ]] and 5-HT2 receptor antagonist methiothepin (0.01-1 microM).""? agonist Question: What is the relation in the sentence ""The positive correlation between << vitamin A >> and [[ immunoglobulin A ]] concentrations might be the result of the vitamin A inductive effect during immunoglobulins A synthesis.""? upregulator Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Structural features of the central cannabinoid CB1 receptor involved in the binding of the specific << CB1 >> antagonist [[ SR 141716A ]].""? antagonist Question: What is the relation in the sentence ""The ultimate carcinogenic Phase I BP metabolite anti-BP-7,8-dihydrodiol-9,10-epoxide (BPDE) can be detoxified by << glutathione >> conjugate formation catalyzed by [[ glutathione S-transferases ]].""? product-of Question: What is the relation in the sentence ""In combination with << clofarabine >>, the ability of resveratrol to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment.""? downregulator Question: What is the relation in the sentence ""<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and [[ receptor for AGE ]] (RAGE).""? indirect-downregulator Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""Purified PAOh1/<< SMO >> oxidizes both spermine (K(m)=1.6 microM) and [[ N(1)-acetylspermine ]] (K(m)=51 microM), but does not oxidize spermidine.""? substrate Question: What is the relation in the sentence ""Importantly, the carboxylic acid of << JY-3-094 >> improves the physicochemical properties of the lead compound, which will facilitate the incorporation of additional hydrophobicity that might enhance [[ Myc ]] inhibitory activity further still.""? inhibitor Question: What is the relation in the sentence ""Taken together, these findings indicate that << antofine >> induces Cx43 gap junction disassembly by the [[ PKCβ ]] signaling pathway.""? activator Question: What is the relation in the sentence ""Our results showed that low dose << BPA >> and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of [[ Oct4 ]] and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein.""? indirect-upregulator Question: What is the relation in the sentence ""Collectively, these data suggest that << cabozantinib >> is a promising agent for inhibiting tumor angiogenesis and metastasis in cancers with dysregulated MET and [[ VEGFR ]] signaling.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 95,"Question: What is the relation in the sentence ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, [[ Tcf1 ]], and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.""? indirect-downregulator Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 ([[ CDK2 ]]), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.""? downregulator Question: What is the relation in the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using << dexamethasone 21-phosphate >> (DEX-P) and midazolam (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.""? activator Question: What is the relation in the sentence ""<< zRetSat A >> also saturated the 13-14 or 7-8 double bonds of all-trans-3,4-didehydroretinol ([[ vitamin A2 ]]), a second endogenous form of vitamin A in zebrafish.""? substrate Question: What is the relation in the sentence ""<< DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005).""? upregulator Question: What is the relation in the sentence ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by [[ thymidine phosphorylase ]] (TP) inside target tissues.""? product-of Question: What is the relation in the sentence ""Taken together, our study demonstrated that << SB365 >> inhibits the AKT/[[ mTOR ]] pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis.""? inhibitor Question: What is the relation in the sentence ""Inhibition of binding of the alpha2-receptor antagonist << [3H]RX821002 >> to recombinant [[ alpha2-receptors ]] by etomidate was tested in human embryonic kidney (HEK293) cells in vitro.""? antagonist Question: What is the relation in the sentence ""Here, we have now found that activation of p38 MAPK by << anisomycin >> potentiated induction of [[ CYP2B6 ]] mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes.""? indirect-upregulator Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities.""? agonist-activator Question: What is the relation in the sentence ""<< 2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid >> (1) is a potent [[ AMPA receptor ]] agonist with moderate affinity for native kainic acid (KA) receptors, whereas (S)-E-4-(2,2-dimethylpropylidene)glutamic acid (3) show high affinity for the GluR5 subtype of KA receptors and much lower affinity for the GluR2 subtype of AMPA receptors.""? agonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""The Schild plots for the competitive antagonists << WB4101 >> and 5-methyl-urapidil against [[ alpha 1a-adrenoceptor ]]-selective agonist methoxamine-induced contraction were linear and had slopes not significantly different from unity, with a pA2 of 9.07 +/- 0.07 (n = 5) for WB4101 and 9.09 +/- 0.05 (n = 3) for 5-methyl-urapidil.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 96,"Given the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", describe the relation. agonist-activator Given the text ""Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]]."", describe the relation. product-of Given the text ""Also in contrast to effects of multiple << METH >> injections, 1) MDMA caused little or no decrease in binding of the [[ DAT ]] ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal DA transport."", describe the relation. downregulator Given the text ""Inhibition of binding of the alpha2-receptor antagonist << [3H]RX821002 >> to recombinant [[ alpha2-receptors ]] by etomidate was tested in human embryonic kidney (HEK293) cells in vitro."", describe the relation. antagonist Given the text ""BDZs and other positive GABA(A)R modulators, including << barbiturates >>, ethanol, and neurosteroids, can also inhibit [[ L-type voltage-gated calcium channels ]] (L-VGCCs), which could contribute to reduced neuronal excitability."", describe the relation. inhibitor Given the text ""The M564G mutated << CrAT >> showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, [[ acetyl-CoA ]]."", describe the relation. substrate Given the text ""<< Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line."", describe the relation. upregulator Given the text ""Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", describe the relation. indirect-upregulator Given the text ""<< DXM >> and 1400W attenuated the mRNA expression of E-selectin and [[ iNOS ]] induced by the costimulation of reIL-4, reTNF-alpha, and LPS."", describe the relation. indirect-downregulator Given the text ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", describe the relation. agonist Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""<< Nitrogen >>-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and [[ Bim ]]-mediated activation of the intrinsic apoptotic pathway."", describe the relation. activator Given the text ""In contrast, aspirin-like nonselective NSAIDs such as << sulindac >> and indomethacin inhibit not only the enzymatic action of the highly inducible, proinflammatory COX-2 but the constitutively expressed, cytoprotective [[ COX-1 ]] as well."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 97,"Consider the text ""The mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and << TRP-2 >> were reduced by [[ artemisinic acid ]] treatment."". Can you identify the relation? indirect-downregulator Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""Terfenadine and astemizole are chemically unrelated to << histamine H1-receptor >> antagonists such as diphenhydramine and [[ chlorpheniramine ]]."". Can you identify the relation? antagonist Consider the text ""We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and [[ chalcone synthase ]] (CHS), and an antioxidant enzyme such as ascorbate peroxidase (APX)."". Can you identify the relation? product-of Consider the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.)."". Can you identify the relation? upregulator Consider the text ""<< IRF3 >> activation induced by MyD88-independent signaling components, TRIF and TBK1, was also downregulated by [[ auranofin ]]."". Can you identify the relation? downregulator Consider the text ""The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition."". Can you identify the relation? agonist Consider the text ""4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, << Cl >>, Br) derivatives are first-generation dual [[ aromatase ]] and sulfatase inhibitors (DASIs)."". Can you identify the relation? inhibitor Consider the text ""Taken together, these data demonstrate that baicalin inhibits the metabolism of << DXM >> in a concentration-dependent manner in rats, possibly through inhibiting hepatic [[ CYP2D ]] and CYP3A activities."". Can you identify the relation? substrate Consider the text ""Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(WAF1/<< CIP1 >>) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2."". Can you identify the relation? indirect-upregulator Consider the text ""Recently, it has been shown that the activation of particular << T2R >> bitter taste receptors is partially involved with the bitter aftertaste sensation of [[ saccharin ]] and acesulfame-K."". Can you identify the relation? activator Consider the text ""This study was designed to determine the gastroprotective properties of cinitapride (<< CNT >>), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and [[ 5-HT2 ]] antagonist, on mucosal injury produced by 50% (v/v) ethanol."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 98,"Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited [[ p16 ]] mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control."", describe the relation. indirect-downregulator Given the text ""Polyclonal antisera to either b5R or << cyt b5 >> significantly inhibited [[ N-hydroxy-4-aminobiphenyl ]] (NHOH-4-ABP) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP)."", describe the relation. substrate Given the text ""The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the << 5-HT3 >> and 5-HT4 receptor antagonist ICS205930 ([[ tropisetron ]]; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM)."", describe the relation. antagonist Given the text ""<< Ozone >> plus PM(2.5) exposure, however, induced CRP, [[ IL-6 ]], CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way."", describe the relation. indirect-upregulator Given the text ""Our data demonstrate that the actions of both tolbutamide and gliclazide are strongly potentiated by 8-pCPT-2'-O-Me-cAMP-AM, that << gliclazide >> can stimulate [[ phospholipase C ]] activity via a partially pertussis toxin-sensitive mechanism, and that 8-pCPT-2'-O-Me-cAMP-AM potentiation of tolbutamide action may involve activation of a 2-APB-sensitive Ca(2+) influx."", describe the relation. activator Given the text ""Platelet-induced << COX-2 >>-dependent [[ PGE2 ]] synthesis in HT29 cells was involved in downregulation of p21(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by rofecoxib(a selective COX-2 inhibitor) and rescued by exogenous PGE2."", describe the relation. product-of Given the text ""Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by << TCDD >>, siRNA-mediated [[ Cx43 ]] knock-down was not sufficient to stimulate proliferation in contact-inhibited cells."", describe the relation. downregulator Given the text ""<< Terbutaline >> (Bricanyl) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients."", describe the relation. agonist Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""BACKGROUND: Since the introduction of the first << cholinesterase >> inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and [[ rivastigmine ]], to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase."", describe the relation. inhibitor Given the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", describe the relation. agonist-activator Given the text ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased [[ catalase ]] (CAT) activity compared with the control."", describe the relation. upregulator Given the text ""<< Imatinib mesylate >> is a [[ tyrosine kinase ]] inhibitor of the ABL, platelet-derived growth factor receptor (PDGFR), and c-kit kinases."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 99,"In this study, we investigated the presence of H(2)S and the expression of << H(2)S >> synthesizing enzymes, CSE and [[ CBS ]], in isolated mouse pancreatic acini. Query: What is the relation? product-of The effects of the << adenosine A3 receptor >> agonist [[ IB-MECA ]] on sodium taurocholate-induced experimental acute pancreatitis. Query: What is the relation? agonist To determine whether << 3,4-methylenedioxymethamphetamine >> (MDMA)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured. Query: What is the relation? downregulator These results suggest that << LTD4 >> increases [[ Aβ peptide ]] burden via activation of CysLT(1)R, which further affects APP levels and activity of β- and γ-secretases via the NF-κB pathway. Query: What is the relation? indirect-upregulator Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the dopamine D1 receptor antagonist SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine) and the << dopamine D2 receptor >> antagonist [[ raclopride ]] (both at 0.003-0.03 mg/kg). Query: What is the relation? antagonist The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator << 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and [[ Nrf-2 ]]-dependent heme oxygenase-1 induction. Query: What is the relation? activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of << TCDD >> inhibition of canonical [[ wnt ]] signaling disrupts prostatic bud formation in mouse urogenital sinus. Query: What is the relation? indirect-downregulator Further, 5HHMF increased specific DNA-binding activity of << Nrf2 >>, and transient knockdown with Nrf2 siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. Query: What is the relation? upregulator They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed COX-1/COX-2 inhibitor ibuprofen; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the << 5-LOX >> inhibitor [[ REV 5901 ]]; and the 5-LOX activating protein (FLAP) inhibitor MK-886. Query: What is the relation? inhibitor Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Carboxylesterases >> hydrolyze esters, [[ amides ]], and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively. Query: What is the relation? substrate Both outward currents were significantly reduced by the mGluR antagonist MCPG and the CHPG-induced current was blocked by the specific << mGluR(5) >> antagonist [[ MTEP ]]. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 100,"Regarding the sentence ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity."", what is the relation? downregulator Regarding the sentence ""UGT1A6 exhibited a significantly higher Vmax and Km values toward both << HFC >> and UDP-glucuronic acid than the other [[ UGTs ]]."", what is the relation? substrate Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]]."", what is the relation? upregulator Regarding the sentence ""Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>[[ parathion ]]>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent."", what is the relation? inhibitor Regarding the sentence ""<< Dexamethasone >> (DEX) inhibited the anti-CD3-induced production of IL-4, [[ IL-5 ]] and IFN-gamma in all 20 clones tested."", what is the relation? indirect-downregulator Regarding the sentence ""Altogether, our findings support a model in which Top2β deficiency promotes << CPT >>-induced apoptosis in quiescent non-S-phase cells, possibly due to RNAP LS depletion and [[ p53 ]] accumulation."", what is the relation? indirect-upregulator Regarding the sentence ""Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist formoterol [[[ eformoterol ]]]."", what is the relation? agonist Regarding the sentence ""Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing << GluR3 >>(L507Y) mutant, but has synergistic effects with [[ lithium ]] on wild-type receptors."", what is the relation? activator Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Selective antagonism of << GluR5 >> kainate-receptor-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons."", what is the relation? antagonist Regarding the sentence ""Uridine 5'-diphosphate- glucuronosyltransferases are colocalized with << carboxylesterases >> and have the potential to further metabolize carboxylic acids to [[ acyl glucuronides ]], but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases."", what is the relation? product-of Regarding the sentence ""Furthermore, << thrombin >> diminished cAMP production in ECs, which were prevented by treatment with [[ genistein ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 101,"Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", can you determine the relation? agonist-activator Regarding ""<< Doxorubicin >> is mainly excreted into the bile via P-glycoprotein (P-gp) and [[ multidrug resistance-associated protein 2 ]] (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily."", can you determine the relation? substrate Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Preincubation for 30 minutes with iloprost, << ciprostene >>, and carbacyclin led to a dose-dependent inhibition of [[ tissue factor ]] expression induced by all three challenging agents."", can you determine the relation? indirect-downregulator Regarding ""Novel analgesic/anti-inflammatory agents: << 1,5-diarylpyrrole nitrooxyalkyl ethers >> and related compounds as [[ cyclooxygenase-2 ]] inhibiting nitric oxide donors."", can you determine the relation? inhibitor Regarding ""<< L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or [[ 2-oxobutyrate ]]."", can you determine the relation? product-of Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric [[ oximes ]], and BT-05 and BT-03 possessing asymmetric structure."", can you determine the relation? activator Regarding ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, [[ cyclin dependent kinase 2 ]] (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", can you determine the relation? downregulator Regarding ""<< CDCA >> induced dose-dependent expression of Cdx2 and [[ MUC2 ]] at both the mRNA and protein levels."", can you determine the relation? indirect-upregulator Regarding ""In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the << dopamine D2 >> agonist [[ apomorphine ]]; however, it is not clear whether both findings share the same biological basis."", can you determine the relation? agonist Regarding ""The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the << 5-HT(1A/1B)-receptor >> antagonist [[ (-)-propranolol ]] and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it."", can you determine the relation? antagonist Regarding ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]]."", can you determine the relation? upregulator Regarding ""Moreover, << simvastatin >> concentration-dependently inhibited the expression of ICAM-1 and induced the expression of [[ CD40 ]] on monocytes."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 102,"Regarding the sentence ""Using cultured human keratinocytes and diabetic rat model, the current study showed that high-<< glucose >> environment enhanced [[ IL-8 ]] production via epidermal growth factor receptor (EGFR) -extracelluar signal-regulated kinase (ERK) pathway in a reactive oxygen species (ROS)-dependent manner in keratinocytes."", what is the relation? indirect-upregulator Regarding the sentence ""Role of organic cation/carnitine transporter 1 in uptake of << phenformin >> and inhibitory effect on [[ complex I ]] respiration in mitochondria."", what is the relation? inhibitor Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", what is the relation? substrate_product-of Regarding the sentence ""Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity."", what is the relation? upregulator Regarding the sentence ""(+)-Tamsulosin, << (-)-tamsulosin >>, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]."", what is the relation? antagonist Regarding the sentence ""<< Amitriptyline >> is a TrkA and [[ TrkB ]] receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity."", what is the relation? agonist Regarding the sentence ""In mechanistic studies, << Silibinin >> decreased the protein level of [[ p34cdc2 ]], which might be the possible molecular mechanism of Silibinin efficacy on the growth inhibition in SGC-7901 cells."", what is the relation? indirect-downregulator Regarding the sentence ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", what is the relation? downregulator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""<< alpha-Tocopherol transfer protein >> (alpha-TTP), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma [[ alpha-tocopherol ]] level by mediating the secretion of alpha-tocopherol by the liver."", what is the relation? substrate Regarding the sentence ""The latter reaction, catalyzed by aspartoacylase (<< ASPA >>), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter."", what is the relation? product-of Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, [[ tert-butylhydroquinone ]], cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."", what is the relation? activator Regarding the sentence ""To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v. << adenosine >> agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S-phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, antagonists, theophylline and 8-p-(sulfophenyl)theophylline as well as [[ enprofylline ]] on ethanol-(i.p.)-induced motor incoordination was evaluated by rotorod."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 103,"The non-selective adenosine receptor antagonist (caffeine), and the selective << adenosine A1 receptor >> antagonist ([[ DPCPX ]]), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice. Please explain the relation. antagonist We found that reduction of the carcinogenic << hydroxylamines >> of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5. Please explain the relation. substrate Consumption of << alcohol >> for 8weeks induced severe liver damage with increases in prognostic indicators such as aspartate transaminase, [[ alanine transaminase ]] in serum whereas co-administration of CNF suppressed their increases. Please explain the relation. indirect-upregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor In human blood, the tested glucocorticoids beclomethasone, << dexamethasone >> and fluticasone inhibited the LPS induced [[ TNF ]] release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced TNF release, with the exception of dexamethasone, was much less pronounced. Please explain the relation. indirect-downregulator A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, << gallic acid >>, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1). Please explain the relation. inhibitor CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Please explain the relation. upregulator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, [[ cyclin A ]], cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Please explain the relation. downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of Both tolbutamide and gliclazide stimulated phospholipase C activity; however, only << gliclazide >> did so independently of its activity at [[ K(ATP) channels ]], and this activity was partially inhibited by pertussis toxin. Please explain the relation. activator N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase (<< EC 3.1.4.45 >>; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome. Please explain the relation. product-of Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (ramelteon, << TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice. Please explain the relation. agonist In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator 4-Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors. << d-Amino acid oxidase >> (DAAO) catalyzes the oxidation of d-amino acids including [[ d-serine ]], a coagonist of the N-methyl-d-aspartate receptor. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 104,"While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early [[ H1-receptor ]] antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity. Question: what is the relation? Answer: agonist Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and [[ prostate-specific antigen ]] (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT). Question: what is the relation? Answer: indirect-downregulator Both risperidone and << 9-hydroxyrisperidone >> are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination. Question: what is the relation? Answer: substrate One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Treatment of C57 BL/6 mice with << bleomycin >> increased fibroblast viability and collagen production and significantly downregulated [[ Nrf2 ]]. Question: what is the relation? Answer: downregulator Ex vivo IC(50) values (COX-1: 105.2 micromol/L; << COX-2 >>: 26.3 micromol/L) of [[ acetaminophen ]] compared favorably with its in vitro IC(50) values. Question: what is the relation? Answer: inhibitor Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h. Question: what is the relation? Answer: upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor Additionally, experiments with the non-desensitizing site-directed mutant GluR3(L507Y) (Stern-Bach, Y., Russo, S., Neuman, M. and Rosenmund, C., A point mutation in the glutamate binding site blocks desensitization of AMPA receptors. Neuron, 21 (1998) 907-918) further confirms that << lithium >> enhances [[ GluR3 ]] responses by reducing desensitization, since lithium's effects are reversed in this mutant. Question: what is the relation? Answer: activator Pretreatment with << pranlukast >> (1.5 ng/mouse, intracerebroventricularly), a [[ CysLT(1)R ]] antagonist, blocked LTD4-induced amyloidogenesis, memory deficits. Question: what is the relation? Answer: antagonist The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator Licofelone almost abolished << 5-LOX >> activity by inhibiting [[ leukotriene B4 ]] generation in rabbit neutrophils and prevented platelet thromboxane B2 production from whole blood. Question: what is the relation? Answer: product-of Anti-diabetic Activity of Swertiamarin is due to an Active Metabolite, << Gentianine >>, that Upregulates [[ PPAR-γ ]] Gene Expression in 3T3-L1 cells. Question: what is the relation? Answer: indirect-upregulator Additionally, these effects of << ATO >> on γ-H2AX, Chk1, Chk2, p53, and p21([[ waf1 ]]/cip1) were reduced by an ATM inhibitor. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 105,"Regarding ""To explore the molecular basis for CPT hypersensitivity in Top2β-deficient cells, we found that upon << CPT >> exposure, the RNA polymerase II large subunit (RNAP LS) became progressively depleted, followed by recovery to nearly the original level in wild-type MEFs, whereas [[ RNAP LS ]] remained depleted without recovery in Top2β-deficient cells."", can you determine the relation? indirect-downregulator Regarding ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", can you determine the relation? agonist-activator Regarding ""Given these findings, a unified PK model including the inhibition of MAO-A- and << CYP2D6 >>-catalyzed [[ 5-MeO-DMT ]] metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models."", can you determine the relation? substrate Regarding ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals."", can you determine the relation? antagonist Regarding ""Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (<< M/TPO-Ag >>) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis."", can you determine the relation? upregulator Regarding ""The in vivo inhibitory effect of harmaline on CYP2D6-catalyzed << bufotenine >> formation was confirmed by in vitro study using purified [[ CYP2D6 ]]."", can you determine the relation? product-of Regarding ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", can you determine the relation? downregulator Regarding ""Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the << TCDD >>-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", can you determine the relation? indirect-upregulator Regarding ""Before the next drug intake, << MAO-A >> inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with [[ toloxatone ]]."", can you determine the relation? inhibitor Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""It is concluded that << D-1997 >> contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the 5-HT1A or [[ 5-HT1B ]] receptor subtypes."", can you determine the relation? activator Regarding ""Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective << alpha(1A)-adrenoceptor >> antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively)."", can you determine the relation? agonist Regarding ""Both fatty acids, but DHA to a lesser extent compared with << EPA >>, selectively and dose-dependently reduced the percentage of [[ cytokine ]]-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)γ-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 106,"The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the << 5-HT(1A/1B)-receptor >> antagonist [[ (-)-propranolol ]] and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it. Please explain the relation. antagonist << β-ionone >> was also shown to induce the expression of cleaved-[[ caspase-3 ]] and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner. Please explain the relation. indirect-upregulator << CGP 12177A >> mediates cardiostimulation by activation of the 'putative' beta(4)-adrenoceptor; however, it has recently been reported that disruption of the [[ beta(1)-adrenoceptor ]] gene abolishes this effect. Please explain the relation. upregulator The upregulation of calpain, tBid and << caspase-3 >> activity were further inhibited by treatment with EGTA in the presence of [[ ALD ]]. Please explain the relation. activator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. Please explain the relation. product-of Dexamethasone (<< DEX >>), betamethasone (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]. Please explain the relation. agonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of [[ DA ]] prevented the MDMA-induced reduction in plasmalemmal DA transport. Please explain the relation. substrate One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of << Licofelone >>, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and [[ cyclooxygenase ]] (COX) enzymes, may have a better cardiovascular profile that cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated antithrombotic effect and a better gastrointestinal tolerability. Please explain the relation. inhibitor These results indicate that << phillyrin >> prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and [[ FAS ]] through LKB1/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity. Please explain the relation. indirect-downregulator Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of VEGF and [[ MMP-9 ]] through Akt pathway in MDA-MB-231 breast cancer cells. Please explain the relation. downregulator In this work a novel approach combining HPLC-UV on-line with oaTOF-MS and ICPMS was applied to investigate in human and rat plasma the metabolism of labelled BK (79/81 Br-Phe5) BrBK in the presence of two new dual << ACE >>/NEP inhibitors (GW660511X and [[ omapatrilat ]]) currently under clinical trial. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 107,"Consider the text ""<< Noradrenaline >> and phenylephrine ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively."". Can you identify the relation? agonist Consider the text ""Moreover, LTD4-induced increases in CysLT(1)R and << NF-κB >> p65 in the brain were also attenuated by [[ pranlukast ]]."". Can you identify the relation? indirect-downregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of spermidine and [[ spermine ]] with a significant accumulation of putrescine and induction of ODC."". Can you identify the relation? product-of Consider the text ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and << activating protein-1 >>, which were increased in [[ fructose ]]-fed rats."". Can you identify the relation? upregulator Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (<< BLT-4 >>), blocked [[ ABCA1 ]]-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM)."". Can you identify the relation? inhibitor Consider the text ""First, we showed that intracerebroventricular administration of << glucose >> in rats increases [[ DBI ]] expression in hypothalamic glial-like tanycytes."". Can you identify the relation? indirect-upregulator Consider the text ""Activation of << AMP-activated Protein Kinase >> and Phosphorylation of Glycogen Synthase Kinase3 β Mediate [[ Ursolic Acid ]] Induced Apoptosis in HepG2 Liver Cancer Cells."". Can you identify the relation? activator Consider the text ""A novel class of << quinoxalines >> has been discovered as antagonists of the IgG:[[ FcRn ]] protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen."". Can you identify the relation? antagonist Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of [[ cyclin D1 ]], cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."". Can you identify the relation? downregulator Consider the text ""It has been claimed that << hCTR1 >>, the human high affinity copper transporter, is the major entry pathway for [[ cDDP ]] and related drugs via a mechanism that mimics copper."". Can you identify the relation? substrate Consider the text ""Furthermore, the EGFR inhibitor << AG1478 >> inhibited EGF-induced MMP-9 expression, cell migration and invasion, as well as the activation of PI3K/Akt, suggesting that PI3K/Akt activation occur downstream of [[ EGFR ]] activation."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 108,"Regarding the sentence ""This observation suggests that << MDMA >>-induced reductions in [[ SERT ]] density do not represent neuroadaptive responses to decreased levels of brain serotonin, but may occur in response to some other stimulus or to the neurotoxic effects of MDMA."", what is the relation? downregulator Regarding the sentence ""The positive correlation between << vitamin A >> and [[ immunoglobulin A ]] concentrations might be the result of the vitamin A inductive effect during immunoglobulins A synthesis."", what is the relation? upregulator Regarding the sentence ""Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as GluN1/GluN2B [[ N-Methyl-D-aspartate Receptor ]] Antagonists."", what is the relation? antagonist Regarding the sentence ""The potency of the selective alpha 1D-adrenoceptor antagonist BMY 7378 against noradrenaline (pA2 = 6.16 +/- 0.13) and of the selective alpha 1A-adrenoceptor antagonist RS-17053 against noradrenaline (pKB = 8.35 +/- 0.10) and against the selective << alpha 1A-adrenoceptor >> agonist [[ A-61603 ]] (pKB = 8.40 +/- 0.09) were too low to account for alpha 1D- and alpha 1A-adrenoceptor involvement."", what is the relation? agonist Regarding the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor Regarding the sentence ""When selectively applied to channels after inducing slow inactivation with a 60-s pulse to -10 mV, << mibefradil >> (1 microM) produced 45% fractional block in Nav1.5 and greater block (88%) in an isoform ([[ Nav1.4 ]]) that slow-inactivates more completely."", what is the relation? inhibitor Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""The treatment of U937 cells with << NRF2 >> inducers including [[ sulforaphane ]] effectively elevated the expression of AKR1B1, 1B10, 1C1, 1C2, and 1C3."", what is the relation? activator Regarding the sentence ""BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, << EC 4.1.1.15 >>) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA)."", what is the relation? product-of Regarding the sentence ""<< Ozone >> plus PM(2.5) exposure, however, induced CRP, IL-6, [[ CK ]], LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way."", what is the relation? indirect-upregulator Regarding the sentence ""One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and << serine hydroxymethyltransferase >> (SHMT, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source."", what is the relation? substrate Regarding the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator Regarding the sentence ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and [[ Wif1 ]], established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD."", what is the relation? indirect-downregulator Regarding the sentence ""EGTA and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid tetrakis (BAPTA), two Ca2+ chelators, but not << nifedipine >>, an [[ L-type Ca2+ channel ]] blocker, prevented GRIP1 degradation."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 109,"In reference to ""There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, << Notch-4 >>, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells."", what is the relation? indirect-upregulator In reference to ""Two beta(2)-agonists, formoterol and << salmeterol >>, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity."", what is the relation? agonist In reference to ""Synthesis and antagonistic activity at << muscarinic receptor >> subtypes of some [[ 2-carbonyl ]] derivatives of diphenidol."", what is the relation? antagonist In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular tyrosine kinase BCR-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, [[ c-FMS ]]."", what is the relation? inhibitor In reference to ""Mutation of arginine 228 to << lysine >> enhances the [[ glucosyltransferase ]] activity of bovine beta-1,4-galactosyltransferase I."", what is the relation? upregulator In reference to ""Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing << GluR3 >>(L507Y) mutant, but has synergistic effects with [[ lithium ]] on wild-type receptors."", what is the relation? activator In reference to ""We have previously reported that TZDs reduce << estrogen >> synthesis by inhibiting [[ aromatase ]] activity in human granulosa cells (HGC)."", what is the relation? product-of In reference to ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""<< HSYA >> suppressed the expression of TLR-4, Myd88, [[ ICAM-1 ]], TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells."", what is the relation? indirect-downregulator In reference to ""The << M564G >> mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, [[ acetyl-CoA ]]."", what is the relation? substrate In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and [[ retinoblastoma protein ]] (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator In reference to ""Preincubation with 1 microM of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) caused a small but significant decrease in << isoprenaline >>-induced E(max), indicating activated PKC-mediated heterologous [[ beta(2)-adrenoceptor ]] desensitization."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 110,"The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Query: What is the relation? agonist-activator RESULTS: << DZN >> induced histophatological damages and elevated the level of cardiac marker [[ CK-MB ]]. Query: What is the relation? indirect-upregulator << Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, [[ pyruvate ]], as well as ketone bodies. Query: What is the relation? substrate Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512). Query: What is the relation? upregulator Preclinical pharmacokinetics and in vitro metabolism of dasatinib (<< BMS-354825 >>): a potent oral multi-targeted kinase inhibitor against SRC and [[ BCR ]]-ABL. Query: What is the relation? inhibitor Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the dopamine D1 receptor antagonist SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine) and the << dopamine D2 receptor >> antagonist [[ raclopride ]] (both at 0.003-0.03 mg/kg). Query: What is the relation? antagonist Expression of the dominant negative mutants rab5A-<< N133I >> or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation. Query: What is the relation? downregulator The << COX >> pathway generates inflammatory [[ prostaglandins ]], while the 5-LOX pathway generates inflammatory leukotrienes. Query: What is the relation? product-of Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Query: What is the relation? activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor << Agmatine >>, locally synthesized, is an endogenous agonist at [[ imidazoline receptors ]], a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter. Query: What is the relation? agonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of << Topiramate >> also partially depressed predominantly [[ AMPA-receptor ]]-mediated EPSCs, but with lower efficacy. Query: What is the relation? indirect-downregulator 4. In the clinical study, small increases in the AUC(0-inf) of simvastatin [mean ratio (90% CI) of 1.34 (1.22, 1.48)] and rosuvastatin [mean ratio (90% CI) of 1.39 (1.30, 1.49)] were observed when co-administered with << GSK1292263 >>, which is consistent with an inhibitory effect on intestinal BCRP and [[ CYP3A4 ]]. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 111,"Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (<< NDGA >>), a [[ lipoxygenase ]] inhibitor on human lung cancer cell lines."". Can you identify the relation? inhibitor Consider the text ""In addition to CYP2B6, << anisomycin >> co-treatment potentiated an increase in [[ CYP2A7 ]] and CYP2C9 mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs."". Can you identify the relation? indirect-upregulator Consider the text ""Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]."". Can you identify the relation? upregulator Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/[[ Akt ]]/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc."". Can you identify the relation? indirect-downregulator Consider the text ""In another experiment, << cyanopindolol >>, an antagonist of the [[ serotonin terminal autoreceptor ]], also prolonged the clearance of 5-HT from the CA3 region."". Can you identify the relation? antagonist Consider the text ""Cholesterol esterase (<< CE >>) induced surface erosion of [[ poly(ethylene carbonate) ]] (PEC) and drug release from PEC under mild physiological environment was investigated."". Can you identify the relation? substrate Consider the text ""Expression of the dominant negative mutants rab5A-<< N133I >> or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation."". Can you identify the relation? downregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""<< Indomethacin >> completely antagonizes [[ CA ]] activity, i.e. abolishes the inhibitory effect of acetazolamide on CA."". Can you identify the relation? activator Consider the text ""Together, this pharmacological profile of subtype-selective betaAR antagonists indicates that in this model, << beta1AR >> activation is responsible for the enhanced hippocampal CA3 network activity initiated by [[ isoproterenol ]]."". Can you identify the relation? agonist Consider the text ""<< PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases (COX) and [[ prostaglandin E synthases ]] (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4)."". Can you identify the relation? product-of Consider the text ""<< Cyclothiazide >> prolonged the decay time constant of [[ AMPA receptor ]]-mediated e.p.s.cs (EC50 35.7 +/- 6.5 microM) with less pronounced effects in slowing e.p.s.c. onset kinetics and increasing e.p.s.c. amplitude."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 112,"Human and rat renin and << angiotensinogen >> genes were downregulated in dTGR and were increased by [[ losartan ]] and cilazapril treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed. Please explain the relation. indirect-upregulator Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats. Please explain the relation. upregulator << PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and [[ Mcl-1 ]], leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. Please explain the relation. indirect-downregulator << HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of p38 [[ mitogen-activated protein kinase ]] (p38 MAPK). Please explain the relation. inhibitor << H1-receptor >> antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which [[ histamine ]] is considered to be of pathogenic importance and conversely to help elucidate the role of histamine in disease, through an evaluation of their influence on disease expression. Please explain the relation. agonist Accordingly, loss of << pip5k1β >> function in FRDA cells was accompanied by decreased [[ PI(4,5)P2 ]] levels and was shown instrumental for destabilization of the actin network and delayed cell spreading. Please explain the relation. product-of Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and [[ hydrogen peroxide ]]) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments. Please explain the relation. activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor Synthesis and antagonistic activity at << muscarinic receptor >> subtypes of some 2-carbonyl derivatives of [[ diphenidol ]]. Please explain the relation. antagonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Please explain the relation. substrate_product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of CA I and [[ CA II ]]. Please explain the relation. downregulator Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam (<< MDZ >>) as an inducer and a substrate to [[ CYP3A ]], respectively. Please explain the relation. substrate We conclude that << cisapride >> is a potent blocker of [[ HERG ]] channels expressed in HEK293 cells. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 113,"<< Cholesterol >> uptake from [[ lipoproteins ]], intracellular vesicle transport and lipid transfer are also modified by oxysterols. Question: what is the relation? Answer: substrate Lisuride dose dependently decreased body temperature in rats with a potency similar to that of the selective << 5-HT(1A) >> agonist [[ LY 293284 ]]. Question: what is the relation? Answer: agonist Treatment of C57 BL/6 mice with << bleomycin >> increased fibroblast viability and collagen production and significantly downregulated [[ Nrf2 ]]. Question: what is the relation? Answer: downregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Question: what is the relation? Answer: agonist-activator Functional and biochemical studies indicated that << TES >> signaling involved activity of the phosphoinositide 3 (PI3) kinase-protein kinase B (Akt) cascade initiated by activation of the [[ androgen receptor ]] and culminated in enhanced production of cGMP and microvascular vasodilation. Question: what is the relation? Answer: activator Culture of HepG2 cells with << griseofulvin >> has now been shown to induce both the formation of intracellular aggregates containing K18 as well as an increase in the abundance of [[ K18 ]] mRNA. Question: what is the relation? Answer: indirect-upregulator Our recent study has demonstrated that coadministration of << monoamine oxidase A >> (MAO-A) inhibitor [[ harmaline ]] (5 mg/kg) increases systemic exposure to 5-MeO-DMT (2 mg/kg) and active metabolite bufotenine. Question: what is the relation? Answer: inhibitor These results indicate that the positive inotropic effect, mediated via << (+/-)-tamsulosin >>- and oxymetazoline-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates. Question: what is the relation? Answer: antagonist To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance. Question: what is the relation? Answer: upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2]. Question: what is the relation? Answer: product-of One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of These results indicate that << phillyrin >> prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and [[ FAS ]] through LKB1/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity. Question: what is the relation? Answer: indirect-downregulator << Sorafenib >> (BAY 43-9006) is a small-molecule inhibitor that has been shown to target members of multiple classes of [[ tyrosine kinases ]] that are known to be involved in tumor cell proliferation and tumor angiogenesis. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 114,"Consider the text ""Activation of AMP-activated Protein Kinase and Phosphorylation of << Glycogen Synthase Kinase3 β >> Mediate [[ Ursolic Acid ]] Induced Apoptosis in HepG2 Liver Cancer Cells."". Can you identify the relation? activator Consider the text ""Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic [[ arginase I ]] and mitochondrial arginase II."". Can you identify the relation? product-of Consider the text ""<< Carboxylesterases >> hydrolyze esters, [[ amides ]], and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively."". Can you identify the relation? substrate Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""The antagonistic property of << rilmenidine >> at [[ human alpha(2A)-adrenoceptors ]] indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved."". Can you identify the relation? antagonist Consider the text ""It has been reported that oligomeric << procyanidins >> of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and [[ insulin ]]-potentiating activities."". Can you identify the relation? upregulator Consider the text ""Based on recent reports that the small molecules, << isatin >> and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase ([[ MAO ]]) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues."". Can you identify the relation? inhibitor Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity."". Can you identify the relation? downregulator Consider the text ""Inhibition > 90% of << IL-2 >> secretion was observed at 1 microM BPB and 10 microM [[ AACOCF3 ]] compared to the respective vehicle control."". Can you identify the relation? indirect-downregulator Consider the text ""OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a [[ peroxisome proliferator-activated receptor alpha ]] (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent."". Can you identify the relation? agonist Consider the text ""The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and Aβ1-42 in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of [[ amyloid precursor protein ]] (APP)."". Can you identify the relation? indirect-upregulator Consider the text ""<< Sulfasalazine >> inhibited tumor necrosis factor alpha-induced activation of endogenous [[ IKK ]] in Jurkat T cells and SW620 colon cells, as well as the catalytic activity of purified IKK-alpha and IKK-beta in vitro."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 115,"In reference to ""Likewise, IL-2 steady-state mRNA expression was inhibited by both << PLA2 >> inhibitors in a concentration-dependent fashion with > 90% inhibition at 1 microM BPB and 20 microM [[ AACOCF3 ]]."", what is the relation? inhibitor In reference to ""<< Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line."", what is the relation? upregulator In reference to ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""Increased immunohistochemical labeling of HIF-1alpha, VEGF, and << BNP >> in the ventricular myocardium was observed in the shunt group and [[ carvedilol ]] again normalized the labeling."", what is the relation? indirect-downregulator In reference to ""Here, we demonstrate that << peptidyl-prolyl cis/trans-isomerase A1 >> (Pin1), an enzyme that catalyzes the conversion of the peptide bond of [[ pSer ]]/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification."", what is the relation? substrate In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS."", what is the relation? product-of In reference to ""Both 5 alpha-NET and << 3 beta,5 alpha-NET >> blocked the [[ PR ]] down-regulation induced by P4 as assessed by Western and Northern blot methods."", what is the relation? indirect-upregulator In reference to ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", what is the relation? substrate_product-of In reference to ""Previously, we showed that the << human kappa-opioid receptor >> (hkor) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged [[ U50,488H ]] treatment."", what is the relation? downregulator In reference to ""Two beta(2)-agonists, << formoterol >> and salmeterol, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity."", what is the relation? agonist In reference to ""BACKGROUND: << Pranlukast >>, a cysteinyl leukotriene receptor 1 ([[ CysLTR1 ]]) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation."", what is the relation? antagonist In reference to ""An amphiphile with branched << poly(ethylene glycol) >> architecture also activated the [[ lectin ]] pathway but only through L-ficolin recognition."", what is the relation? activator In reference to ""We have previously demonstrated that phosphorylation of << Fas-associated death domain-containing protein >> (FADD) at 194 serine through c-jun NH2-terminal kinase (JNK) activation sensitizes breast cancer cells to chemotherapy through accelerating cell cycle arrest at G2/M, and that Bcl-2 phosphorylation downstream of JNK/FADD plays an important role in cell growth suppression by [[ paclitaxel ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 116,"Regarding ""Cotreatment with U0126 and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of << sulindac >> treatment on ERK1/2, JNK, and [[ beta-catenin ]]."", can you determine the relation? indirect-downregulator Regarding ""Thus prolonged activation of NMDA receptors in hippocampal neurons reduced << GABAR δ subunit >> expression through [[ Ca2+ ]] entry and at least in part by ERK1/2 activation."", can you determine the relation? downregulator Regarding ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""On study day 10, the acute effects of << candoxatril >> were similar to those on day 1 (i.e., [[ ANP ]] was further increased, aldosterone was suppressed, and right and left ventricular filling pressures were decreased)."", can you determine the relation? indirect-upregulator Regarding ""<< Ambrisentan >> is an [[ endothelin type A (ET(A))-selective receptor ]] antagonist that is metabolized primarily by glucuronidation but also undergoes oxidative metabolism by CYP3A4."", can you determine the relation? antagonist Regarding ""Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II."", can you determine the relation? product-of Regarding ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound [[ BT-07-4M ]], TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure."", can you determine the relation? activator Regarding ""<< S1P >> activated phosphatidylinositol 3-kinase (PI3K)/Akt signaling, leading to the inhibition of [[ glycogen synthase kinase-3β ]] and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells."", can you determine the relation? inhibitor Regarding ""The << CYP2B6*6 >> Allele Significantly Alters the N-demethylation of [[ Ketamine ]] Enantiomers In Vitro."", can you determine the relation? substrate Regarding ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."", can you determine the relation? upregulator Regarding ""The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition."", can you determine the relation? agonist Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Cyclooxygenase-1 (<< COX-1 >>) inhibitors (flurbiprofen, ketoprofen and [[ ketrolack ]]) attenuated the nicotine-induced contraction in a concentration-dependent manner, and cyclooxygenase-2 (COX-2) inhibitors at high concentrations (nimesulide and NS-389) slightly attenuated the contraction."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 117,"Consider the text ""To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance."". Can you identify the relation? upregulator Consider the text ""We conclude that << mPGES1 >> mediates acid-induced increase in [[ PGE2 ]] production and cell proliferation."". Can you identify the relation? product-of Consider the text ""Again, inhibition of the actin-activated << myosin >> Mg2+-ATPase and myosin filament assembly by felodipine and the [[ p-chloro ]] analogue could be reversed by raising the calmodulin concentration."". Can you identify the relation? inhibitor Consider the text ""Growth inhibition of these tumor cell lines was associated with the dephosphorylation of EGFR, HER2, and HER3, accompanied by the loss of association of HER3 with << phosphatidylinositol 3-kinase >>[[ phosphatidylinositol ]] 3-kinase, and down-regulation of Akt activity."". Can you identify the relation? substrate Consider the text ""Nizatidine (<< LY139037 >>), a selective [[ histamine H2-receptor ]] antagonist, is a potent inhibitor of gastric acid secretion."". Can you identify the relation? antagonist Consider the text ""These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and << oxymetazoline >>-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates."". Can you identify the relation? agonist Consider the text ""<< DBDCT >> also caused the phosphorylation of [[ JNK ]] and p38(MAPK)."". Can you identify the relation? activator Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of [[ nitrate reductase ]], glutamine synthetase, glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings."". Can you identify the relation? downregulator Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""The mRNA levels of << microphthalmia-associated transcription factor >> (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment."". Can you identify the relation? indirect-downregulator Consider the text ""These results suggest that << LTD4 >> increases [[ Aβ peptide ]] burden via activation of CysLT(1)R, which further affects APP levels and activity of β- and γ-secretases via the NF-κB pathway."". Can you identify the relation? indirect-upregulator Consider the text ""Agents which have recently been shown to block << cyclin D1 >> translation by regulating calcium levels are the unsaturated essential fatty acid, eicosapentaenoic acid (EPA), the antidiabetic thiazolidinediones, and the antifungal agent, [[ clotrimazole ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 118,"Regarding the sentence ""The beta subunit has been cloned and shown to lower the K(m) of << methionine adenosyltransferase II alpha2 >> (the MAT2A product) for [[ methionine ]] and to render the enzyme more susceptible to S-adenosylmethionine inhibition."", what is the relation? substrate Regarding the sentence ""After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and [[ histamine ]]."", what is the relation? agonist Regarding the sentence ""Compared pharmacological characteristics in humans of racemic cetirizine and << levocetirizine >>, two [[ histamine H1-receptor ]] antagonists."", what is the relation? antagonist Regarding the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""<< 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and [[ Nrf-2 ]]-dependent heme oxygenase-1 induction."", what is the relation? activator Regarding the sentence ""Ferredoxin 1 (<< FDX1 >>; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues."", what is the relation? product-of Regarding the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator Regarding the sentence ""The present studies were undertaken to determine whether stable analogues of << prostacyclin >>, a potent endothelium-derived platelet inhibitor and vasodilator, could inhibit [[ tissue factor ]] expression by human monocytic cells."", what is the relation? indirect-downregulator Regarding the sentence ""Using the << mTOR >> inhibitor [[ PP242, ]] we found that TGFβ-induced both early and sustained activation of TORC1 and TORC2 was necessary for deptor suppression."", what is the relation? inhibitor Regarding the sentence ""<< HSYA >> treatment also decreased [[ NF-κB ]] p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK)."", what is the relation? downregulator Regarding the sentence ""Results showed that neonatal << quinpirole >> treatment induced [[ D2 ]] priming that was eliminated by olanzapine treatment."", what is the relation? indirect-upregulator Regarding the sentence ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase ([[ CAT ]]) activity compared with the control."", what is the relation? upregulator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent << CYP3A >> inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or [[ boceprevir ]], and therefore their coadministration is contraindicated."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 119,"In reference to ""The in vivo inhibitory effect of harmaline on CYP2D6-catalyzed << bufotenine >> formation was confirmed by in vitro study using purified [[ CYP2D6 ]]."", what is the relation? product-of In reference to ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", what is the relation? agonist-activator In reference to ""These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves."", what is the relation? agonist In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced [[ c-fos ]] and c-jun expression relative to control."", what is the relation? indirect-upregulator In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53."", what is the relation? upregulator In reference to ""Preclinical pharmacokinetics and in vitro metabolism of << dasatinib >> (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and [[ BCR ]]-ABL."", what is the relation? inhibitor In reference to ""Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes [[ arachidonic acids ]] to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on the cardiovascular system."", what is the relation? substrate In reference to ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and [[ obidoxime ]] from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure."", what is the relation? activator In reference to ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""Clinical effects of << pranlukast >>, an oral [[ leukotriene receptor ]] antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial."", what is the relation? antagonist In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, [[ cyclin E ]], cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator In reference to ""<< Tomudex >> treatment resulted in the decrease in [[ p27(kip1) ]] expression, with an increase in cyclin E and cdk2 protein expression and kinase activities 24 h after a 2-h exposure."", what is the relation? indirect-downregulator In reference to ""Several effects of << polyphenols >> are useful in this scenario, including a reduction in the activities of cytokines and modulation of cellular metabolism through histone deacetylase inhibitors, [[ AMPK ]] activators, calorie-restriction mimetics or epigenetic regulators."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 120,"Question: What is the relation in the sentence ""These results indicate transcription of << FDX1 >> is regulated by the NR5A family and [[ cAMP ]] signaling, and participates in steroid hormone production in ovarian granulosa cells.""? indirect-upregulator Question: What is the relation in the sentence ""Furthermore, these << phosphorylated flavonoids >> demonstrated good to high selectivity for CEase over [[ AChE ]], which only showed micromolar potency inhibition of AChE.""? inhibitor Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""Saturated << palmitic and stearic acids >> increased ceramides, up-regulated PTP1B, and had AKt and [[ PTP1B ]] phosphorylation at Ser 50 impaired.""? activator Question: What is the relation in the sentence ""<< 2-(2-Aminoethyl)-quinoline >> (D-1997): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery.""? agonist Question: What is the relation in the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons.""? agonist-activator Question: What is the relation in the sentence ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).""? downregulator Question: What is the relation in the sentence ""<< Terfenadine >> and astemizole are chemically unrelated to [[ histamine H1-receptor ]] antagonists such as diphenhydramine and chlorpheniramine.""? antagonist Question: What is the relation in the sentence ""Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released << glutamate >> and its conversion to glutamine through the enzyme glutamine synthetase ([[ GS ]]).""? substrate Question: What is the relation in the sentence ""Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II.""? product-of Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Moreover, << licofelone >> inhibited COX-2 and [[ 5-LOX ]] protein expression in vascular lesions.""? indirect-downregulator Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53.""? upregulator Question: What is the relation in the sentence ""Results indicate that AM4054 serves as an effective CB(1) discriminative stimulus, with an onset and time course of action comparable with that of the << CB(1) >> agonist Δ(9)-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the [[ AM4054 ]] dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 121,"The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), << nuclear factor kappa B >> (NF-κB) genes expression in [[ cisplatin ]] injected rats. what is the relation? indirect-downregulator Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.). what is the relation? upregulator In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, [[ MBD-2 ]] and MBD-3), in MEF cells by the proteasomal pathway. what is the relation? downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. what is the relation? agonist-activator Upon activation by << phenobarbital >>, [[ nuclear receptor ]] CAR binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter. what is the relation? activator << Theophylline >> exposure resulted in a sustained increase in mRNA expression for CysS and [[ PDE3A ]], but PDE4D gene expression was unchanged. what is the relation? indirect-upregulator These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by << peroxynitrite >> formed from [[ xanthine oxidase ]]-generated superoxide and NO. what is the relation? product-of However, << topiramate >> at low concentrations causes slow inhibition of [[ GluR5 ]] kainate receptor-mediated synaptic currents in the basolateral amygdala, indicating that it may protect against seizures, at least in part, through suppression of GluR5 kainate receptor responses. what is the relation? inhibitor Synthesis and antagonistic activity at << muscarinic receptor >> subtypes of some [[ 2-carbonyl ]] derivatives of diphenidol. what is the relation? antagonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. what is the relation? substrate_product-of In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the << dopamine D2 >> agonist [[ apomorphine ]]; however, it is not clear whether both findings share the same biological basis. what is the relation? agonist In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of << cAMP >> to AMP by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase. what is the relation? substrate Osteoblasts survive the << arsenic trioxide >> treatment by activation of [[ ATM ]]-mediated pathway. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 122,"Question: What is the relation in the sentence ""8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by tolbutamide was markedly inhibited by [[ 2-APB ]] (25 μM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 μM).""? indirect-downregulator Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""In this study, we assessed the effects of << clopidogrel >> and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with [[ CYP2B6 ]] polymorphisms in humans.""? inhibitor Question: What is the relation in the sentence ""Thus, << SFO >> contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and [[ IL-8 ]] and cell apoptosis in plaque.""? activator Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons.""? agonist-activator Question: What is the relation in the sentence ""We confirm the correlation between higher << hCTR1 >> levels and higher [[ Pt ]]-drug uptake in tumor cells sensitive to the drug.""? substrate Question: What is the relation in the sentence ""Moreover, recent in vitro studies suggest that << memantine >> abrogates beta-amyloid ([[ Abeta ]]) toxicity and possibly inhibits Abeta production.""? downregulator Question: What is the relation in the sentence ""In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the PGE1 mediated stimulation of << Na,K-ATPase beta >> subunit gene transcription includes the stimulatory effect of [[ 17-phenyl trinor PGE2 ]], as well as the inhibitory effects of SC-51089.""? indirect-upregulator Question: What is the relation in the sentence ""Local LC citalopram effect was abolished by LC presence of the 5-HT3 receptor antagonist MDL72222 (1 μM) but not the << 5-HT1/2 >> receptor antagonist [[ methiothepin ]] (1 μM).""? antagonist Question: What is the relation in the sentence ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity.""? upregulator Question: What is the relation in the sentence ""Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist [[ acetylcholine ]] (ACh) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump.""? agonist Question: What is the relation in the sentence ""<< PIP5K1B >> encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2].""? product-of Question: What is the relation in the sentence ""Furthermore, they suggest that TRPML1 works in concert with << ZnT4 >> to regulate [[ zinc ]] translocation between the cytoplasm and lysosomes.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 123,"These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. Question: what is the relation? Answer: upregulator Also, << vinblastine >> enhances the phosphorylation of [[ Ras homologous protein A ]], the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α. Question: what is the relation? Answer: activator << GCS >> therapy results in reduced mRNA expression of [[ interleukin-4 ]] (IL-4) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma. Question: what is the relation? Answer: indirect-downregulator The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by << Tomudex >> indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of [[ thymidylate synthase ]] and resultant dNTP pool imbalance. Question: what is the relation? Answer: inhibitor The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Question: what is the relation? Answer: substrate_product-of Cardiac effects of the << beta 3-adrenoceptor >> agonist [[ BRL35135 ]] in man. Question: what is the relation? Answer: agonist The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the << 5-HT(3/4)-receptor >> antagonist [[ tropisetron ]] did not affect it. Question: what is the relation? Answer: antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor << Ozone >> plus PM(2.5) exposure, however, induced CRP, [[ IL-6 ]], CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way. Question: what is the relation? Answer: indirect-upregulator Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]. Question: what is the relation? Answer: downregulator First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (<< ABCA1 >>)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner. Question: what is the relation? Answer: product-of At normal pH (7.4) and temperature (37 degrees C), the uptake of 1 microM << cefadroxil >> was reduced by 83% in PEPT2(-/-) mice as compared with [[ PEPT2 ]](+/+) mice (p < 0.001). Question: what is the relation? Answer: substrate Cabozantinib (<< XL184 >>), a novel [[ MET ]] and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 124,"In reference to ""In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the << dopamine D2 >> agonist [[ apomorphine ]]; however, it is not clear whether both findings share the same biological basis."", what is the relation? agonist In reference to ""<< cAspAT >> activity, as well as the incorporation of [(14)C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was stimulated by the thiazolidinedione ([[ TZD ]]) rosiglitazone."", what is the relation? activator In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""Transduction with constitutively active forms of GSK-3β could protect against the downregulation of << p65 >> and upregulation of cleaved-PARP that are induced by [[ cinobufagin ]] treatment."", what is the relation? indirect-downregulator In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively."", what is the relation? upregulator In reference to ""These protective effects were abolished by glucocorticoid receptor (GR) antagonist RU486 or p-ERK inhibitor U0126 rather than << estrogen receptor α >> antagonist [[ ICI 82,780 ]]."", what is the relation? antagonist In reference to ""<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins ([[ Bax ]], Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27."", what is the relation? indirect-upregulator In reference to ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator In reference to ""It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and [[ BRCA2 ]] mutations, although preliminary evidence favors benefit for at least those with a BRCA2 mutation."", what is the relation? downregulator In reference to ""Catecholamines (adrenaline, << noradrenaline >> and dopamine) are potent inhibitors of [[ phenylalanine 4-monooxygenase ]] (phenylalanine hydroxylase, EC 1.14.16.1)."", what is the relation? inhibitor In reference to ""Moreover, a normal level of expression of PSS1 and/or << PSS2 >> is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis."", what is the relation? product-of In reference to ""In the present study, we have evaluated possible participation of << monocarboxylate transporters >> (MCTs) responsible for the bidirectional membrane transport of [[ pyruvate ]] in the cytoprotective property in osteoblasts."", what is the relation? substrate In reference to ""Sedation and << histamine H1-receptor >> antagonism: studies in man with the enantiomers of chlorpheniramine and [[ dimethindene ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 125,"Consider the text ""Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, << pelargonidin >> can bind to and activate the [[ AhR ]] and AhR-dependent gene expression, and pelargonidin and delphinidin inhibit the CYP1A1 catalytic activity."". Can you identify the relation? activator Consider the text ""BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, << EC 4.1.1.15 >>) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA)."". Can you identify the relation? product-of Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""On the other hand, in patients with a mean serum << carvedilol >> level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l."". Can you identify the relation? downregulator Consider the text ""<< CYP1A1 >> and CYP1A2 mRNAs were also increased by [[ pelargonidin ]] in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."". Can you identify the relation? indirect-upregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases ([[ COX ]]) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4)."". Can you identify the relation? substrate Consider the text ""In further studies, the diuretic effects of the << CB1 >> agonist [[ AM4054 ]] were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]."". Can you identify the relation? agonist Consider the text ""Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the << dopamine D1 receptor >> antagonist SCH 39166 ([[ (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine ]]) and the dopamine D2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg)."". Can you identify the relation? antagonist Consider the text ""Furthermore, << V(5+) >> significantly inhibited the TCDD-induced [[ AhR ]]-dependent luciferase activity."". Can you identify the relation? indirect-downregulator Consider the text ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats."". Can you identify the relation? upregulator Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""CONCLUSION: Our results indicate that << pranlukast >> inhibits [[ IL-5 ]] synthesis via a mechanism distinct from CysLTR1 antagonism."". Can you identify the relation? inhibitor Consider the text ""Chromatographic analysis of the metabolism of 14C-labeled arachidonic acid in this system revealed that PB-dependent inactivation of << PHS >> is markedly increased in the presence of 100 microM [[ H2O2 ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 126,"Regarding ""<< Indomethacin >> abolished the inhibitory effect of acetazolamide on CA I and [[ CA II ]]."", can you determine the relation? activator Regarding ""This stimulation was attenuated by the << Pak >> inhibitor 2,2'-dihydroxy-1,1'-dinaphthyldisulfide ([[ IPA3 ]]) or dominant-negative Pak1."", can you determine the relation? inhibitor Regarding ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", can you determine the relation? agonist-activator Regarding ""In addition, the number and area of << glutathione S-transferase placental form >> (GST-P) positive foci and proliferating cell nuclear antigen (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg [[ MEG ]] compared with the control animals."", can you determine the relation? indirect-upregulator Regarding ""Suppression of Src/ERK and << GSK-3 >>/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells."", can you determine the relation? downregulator Regarding ""<< Astemizole >>, a potent [[ histamine H1-receptor ]] antagonist: effect in allergic rhinoconjunctivitis, on antigen and histamine induced skin weal responses and relationship to serum levels."", can you determine the relation? antagonist Regarding ""Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in [[ ERK1/2 ]] and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR."", can you determine the relation? upregulator Regarding ""Docetaxel is a semisynthetic << taxane >> that inhibit tumor growth by induction of microtubule stabilization and promotion of [[ bcl-2 ]] inactivation, which induce apoptosis."", can you determine the relation? indirect-downregulator Regarding ""<< QR2 >> catalyzes the two-electron reduction of menadione via the oxidation of [[ N-alkylated ]] or N-ribosylated nicotinamides."", can you determine the relation? substrate Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase ([[ CBS ]])."", can you determine the relation? product-of Regarding ""This inhibition was blocked when mice were pretreated with the selective << H3R >> agonist [[ R-(alpha)-methyl-histamine ]] (10 mg/kg)."", can you determine the relation? agonist Regarding ""Acute and chronic PLZ administration increase brain GABA levels, an effect due, at least in part, to an inhibition of the activity of the << GABA >> metabolizing enzyme, GABA transaminase ([[ GABA-T ]])."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 127,"<< Aldosterone >>-induced [[ ENaC ]] and basal Na(+)/K(+)-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIIIβ trans Golgi signalling in M1 cortical collecting duct cells. Question: what is the relation? Answer: indirect-upregulator The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure. Question: what is the relation? Answer: agonist In vivo << lorglumide >> antagonizes the contraction of the gall bladder of the guinea pig and of the dog provoked by i.v. [[ CCK-8 ]] or ceruletide (caerulein). Question: what is the relation? Answer: antagonist The << BH(4) >> treatment was associated with a 2-fold increase in [[ eNOS ]] activity as well as a 70% reduction in endothelial O(2)(-) production compared with those in fructose-fed rats. Question: what is the relation? Answer: activator In this study, we found that << 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase ([[ iNOS ]]) in BV2 microglia. Question: what is the relation? Answer: indirect-downregulator For determination of [PA+<< Pli >>]-activity, [[ arginine ]] was added after this incubation. Question: what is the relation? Answer: substrate << Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of [[ cytochrome c ]] to the cytosol induced by DZN. Question: what is the relation? Answer: downregulator In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: agonist-activator A series of phenolic acids and << phenol >> natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1). Question: what is the relation? Answer: inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Question: what is the relation? Answer: substrate_product-of Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]. Question: what is the relation? Answer: upregulator BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA). Question: what is the relation? Answer: product-of When combined, mianserin antagonized the effects of the full kappa-opioid receptor agonists in [(35)S]GTPgammaS assays and reduced the stimulation of p38 << MAPK >> and ERK1/2 phosphorylation by [[ dynorphin A ]]. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 128,"Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""G6PC2: A Negative Regulator of Basal << Glucose >>-Stimulated [[ Insulin ]] Secretion."". Can you identify the relation? upregulator Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Overall, higher alcohol production was reduced by << ammonium >> supplementation, and this can be correlated with a general downregulation of genes encoding [[ decarboxylases ]] and dehydrogenases of the Ehrlich pathway."". Can you identify the relation? indirect-downregulator Consider the text ""Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [[[ R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate ]]], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia."". Can you identify the relation? agonist Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""On the basis of our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxification of << arylhydroxylamine >> carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R) and [[ cytochrome b5 ]] (cyt b5)."". Can you identify the relation? substrate Consider the text ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (<< 1O2 >>) donor chloramine T (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."". Can you identify the relation? downregulator Consider the text ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to << NRF2 >> inducers ([[ sulforaphane ]], tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."". Can you identify the relation? activator Consider the text ""Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, [[ prazosin ]], tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials."". Can you identify the relation? antagonist Consider the text ""These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by << peroxynitrite >> formed from [[ xanthine oxidase ]]-generated superoxide and NO."". Can you identify the relation? product-of Consider the text ""Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor << manumycin A >> caused elevation of [[ ApoA-I ]] secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes."". Can you identify the relation? indirect-upregulator Consider the text ""The effects of two reversible, predominantly << monoamine oxidase-A >> (MAO-A) inhibitors, [[ moclobemide ]] (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects."". Can you identify the relation? inhibitor Consider the text ""In the current study, we show that systematic modification of an << aminoalkylindole >> scaffold identifies two new compounds with dual [[ CB1R ]] antagonist/CB2R agonist activity."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 129,"Regarding ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, [[ p38 ]], inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α."", can you determine the relation? activator Regarding ""To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance."", can you determine the relation? upregulator Regarding ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", can you determine the relation? agonist-activator Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""The mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and << TRP-2 >> were reduced by [[ artemisinic acid ]] treatment."", can you determine the relation? indirect-downregulator Regarding ""While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early [[ H1-receptor ]] antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity."", can you determine the relation? agonist Regarding ""<< (125)I-Cyanopindolol >> saturation binding in Adv.beta(1) myocytes demonstrated approximately 18-fold increase in [[ beta(1)-adrenoceptors ]]."", can you determine the relation? indirect-upregulator Regarding ""METHODS: << Cyclooxygenase >> activity and selectivity was determined in vitro by measuring prostaglandin E(2) ([[ PGE(2) ]]) production following incubation of varying concentrations of NSAID with human recombinant COX-1 or COX-2 and arachidonic acid."", can you determine the relation? product-of Regarding ""Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood << harmaline >>, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-[[ CYP2D6 ]] mouse models."", can you determine the relation? inhibitor Regarding ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase ([[ SOD ]]) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control."", can you determine the relation? downregulator Regarding ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: << 4-methoxy-2-naphthylamide >> of L-alanine for [[ aminopeptidase N ]], 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B."", can you determine the relation? substrate Regarding ""Terfenadine and astemizole are chemically unrelated to << histamine H1-receptor >> antagonists such as [[ diphenhydramine ]] and chlorpheniramine."", can you determine the relation? antagonist Regarding ""Unlike GW660511X, << omapatrilat >> abolished the production of BrBK1-5 and BrBK1-7, suggesting a better [[ ACE ]] inhibition effect over GW660511X as no NEP activity was found."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 130,"Question: What is the relation in the sentence ""Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of CA I and [[ CA II ]].""? downregulator Question: What is the relation in the sentence ""<< DNA methyltransferase 3a >> expression was increased in all [[ BPA ]] males and BPA 0.5 females and reduced in BPA 200 females.""? indirect-upregulator Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]].""? agonist-activator Question: What is the relation in the sentence ""<< Memantine >> is an uncompetitive (channel blocking) [[ NMDA receptor ]] antagonist.""? antagonist Question: What is the relation in the sentence ""Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, << IL-1β >>, IL-18, IL-17A and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]].""? indirect-downregulator Question: What is the relation in the sentence ""Troglitazone inhibited the antigen-induced production of LTB(4), C(4) and E(4) and the potency of the inhibition was comparable to that of << zileuton >>, a specific inhibitor of 5-lipoxygenase ([[ 5-LOX ]]) and a clinically used anti-asthmatic drug.""? inhibitor Question: What is the relation in the sentence ""<< LDH >> is responsible for pyruvate conversion to [[ lactate ]] through glycolysis.""? product-of Question: What is the relation in the sentence ""Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration.""? upregulator Question: What is the relation in the sentence ""alpha-Tocopherol transfer protein (<< alpha-TTP >>), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma [[ alpha-tocopherol ]] level by mediating the secretion of alpha-tocopherol by the liver.""? substrate Question: What is the relation in the sentence ""The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition.""? agonist Question: What is the relation in the sentence ""Thus, << SFO >> contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and [[ IL-8 ]] and cell apoptosis in plaque.""? activator Question: What is the relation in the sentence ""In another experiment, topical application of CFB, CFE or << CLS >> prior to UVB irradiation (200mJ/cm(2)) on BALB/c mice, inhibited the UVB-elevated protein levels of COX-2, iNOS, and [[ TNF-α ]].""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 131,"Given the text ""We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as [[ l-phenylalanine ammonia-lyase ]] (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as ascorbate peroxidase (APX)."", describe the relation. product-of Given the text ""The vascular protective effects of << kinsenoside >> were speculated to be attributed to oxidative stress inhibition and the reduction of [[ nuclear factor kappa B ]] (NF-κB) mRNA expression levels in high glucose conditions."", describe the relation. indirect-downregulator Given the text ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", describe the relation. agonist-activator Given the text ""We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the << heterocyclic amine >> 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5."", describe the relation. substrate Given the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", describe the relation. agonist Given the text ""Cross-inhibition of << SR-BI >>- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and [[ glyburide ]]."", describe the relation. inhibitor Given the text ""Labetalol (> or = 3 x 10(-8) M) and << dilevalol >> (> or = 10(-8) M) caused surmountable antagonism of the isoprenaline responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors."", describe the relation. antagonist Given the text ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam (<< MDZ >>) as an inducer and a substrate to [[ CYP3A ]], respectively."", describe the relation. activator Given the text ""Additionally, << MPTP >> significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in [[ Bax ]] expression, cytochrome C translocation to the cytosol, andcleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment."", describe the relation. indirect-upregulator Given the text ""Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the [[ MDMA ]]-induced reduction in plasmalemmal DA transport."", describe the relation. downregulator Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""<< DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005)."", describe the relation. upregulator Given the text ""Accordingly, docking of different << COX >> inhibitors, including selective and non-selective ligands: rofecoxib, ketoprofen, suprofen, [[ carprofen ]], zomepirac, indomethacin, diclofenac and meclofenamic acid were undertaken using the AMBER program."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 132,"The positive correlation between vitamin A and << immunoglobulin A >> concentrations might be the result of the [[ vitamin A ]] inductive effect during immunoglobulins A synthesis. Query: What is the relation? upregulator The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the << 5-HT1A >> receptor antagonist [[ spiroxatrine ]] (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM). Query: What is the relation? antagonist There was also an increase in c-kit, Trio, Rho-A, << Rac-3 >>, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells. Query: What is the relation? indirect-upregulator << Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 ([[ MCP-1 ]]), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE). Query: What is the relation? indirect-downregulator These data suggest that endothelial << NO >> synthesis depends on the activity of [[ arginase II ]] in mitochondria and l-arginine carriers in cell membrane. Query: What is the relation? product-of BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific << alpha2-adrenoceptor >> agonists of the type such as [[ dexmedetomidine ]]. Query: What is the relation? agonist The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator We previously reported that << aminoglycoside >> antibiotics reduce [[ SGLT1 ]]-dependent glucose transport in pig proximal tubular epithelial LLC-PK1 cells in parallel with the order of their nephrotoxicity. Query: What is the relation? downregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Catecholamines (<< adrenaline >>, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, [[ EC 1.14.16.1 ]]). Query: What is the relation? inhibitor In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor This study assessed changes in myocardial ALDH2 expression in the diabetic rat, in particular the diabetic rat pretreated with << ALDH2 >> activator ethanol ([[ EtOH ]]). Query: What is the relation? activator Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (<< Pin1 >>), an enzyme that catalyzes the conversion of the peptide bond of pSer/[[ pThr ]]-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification. Query: What is the relation? substrate In addition to effects on cell proliferation, << DHT >> increased the percentage of alkaline phosphatase ([[ ALP ]]) positive cells in all three bone cell systems tested, and this effect was inhibited by antiandrogens. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 133,"<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and [[ p27 ]]. Please explain the relation. indirect-upregulator The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific). Please explain the relation. agonist PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (<< 5-FU >>) by [[ thymidine phosphorylase ]] (TP) inside target tissues. Please explain the relation. product-of Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of << L-alanine >> for [[ aminopeptidase N ]], 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B. Please explain the relation. substrate Polymorphisms in dopamine transporter (<< SLC6A3 >>) are associated with stimulant effects of [[ D-amphetamine ]]: an exploratory pharmacogenetic study using healthy volunteers. Please explain the relation. activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor Both 5'-AMN and << 5'-MABN >> had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and [[ μ-receptor ]] antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum. Please explain the relation. antagonist The inhibition of << aminopeptidase >> activity in the presence of bestatin and [[ puromycin ]] inhibitors was also investigated. Please explain the relation. inhibitor Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity. Please explain the relation. downregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Please explain the relation. agonist-activator Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h. Please explain the relation. upregulator Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and [[ prostate-specific antigen ]] (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT). Please explain the relation. indirect-downregulator The current comprehensive losartan clinical end-point programme (4 large scale morbidity/mortality trials) should provide evidence regarding the efficacy of direct blockade of the << AT(1) receptor >> with [[ losartan ]] compared to standard therapy: 1) The Losartan Heart Failure Survival Study - ELITE II, 2) The Losartan Post-Myocardial Infarction Survival Study - OPTIMAAL, 3) The Losartan Hypertension Survival Study - LIFE and 4) The Losartan Renal Protection Study - RENAAL. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 134,"Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). Please explain the relation. upregulator Second, << ICRF-187 >>, a Top2 catalytic inhibitor known to deplete [[ Top2β ]], specifically sensitized MEFs to CPT. Please explain the relation. inhibitor Therefore, pretreatment tumor gene expression profiling of ASS and OTC could aid in predicting tumor response to << arginine >> depletion with [[ arginine-depleting enzymes ]]. Please explain the relation. substrate In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the PGE1 mediated stimulation of << Na,K-ATPase beta >> subunit gene transcription includes the stimulatory effect of [[ 17-phenyl trinor PGE2 ]], as well as the inhibitory effects of SC-51089. Please explain the relation. indirect-upregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Please explain the relation. substrate_product-of << Adrenaline >> inhibits [[ insulin ]] secretion via pertussis toxin-sensitive mechanisms. Please explain the relation. indirect-downregulator Humans with << FSH beta >> gene mutations tend to have a more severe phenotype than those with FSHR gene mutations, although infertility and varying degrees of impaired sex [[ steroid ]] production occur in both types of mutations. Please explain the relation. product-of Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced butein-induced HO-1 expression, and << butein >> treatment led to increased [[ JNK ]] phosphorylation. Please explain the relation. activator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator Also in contrast to effects of multiple << METH >> injections, 1) MDMA caused little or no decrease in binding of the [[ DAT ]] ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal DA transport. Please explain the relation. downregulator << Kynurenic acid >> (KA) is an endogenous [[ glutamate receptor ]] antagonist at the level of the different ionotropic glutamate receptors. Please explain the relation. antagonist << 2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid >> (1) is a potent [[ AMPA receptor ]] agonist with moderate affinity for native kainic acid (KA) receptors, whereas (S)-E-4-(2,2-dimethylpropylidene)glutamic acid (3) show high affinity for the GluR5 subtype of KA receptors and much lower affinity for the GluR2 subtype of AMPA receptors. Please explain the relation. agonist RA is known to induce expression of the Burkitt's lymphoma receptor 1 (BLR1) gene which propels RA-induced cell cycle arrest and differentiation of HL-60 human myeloblastic leukemia cells, motivating the present analysis of transcriptional regulation of << blr1 >> expression by [[ RA ]]. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 135,"Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity."", describe the relation. upregulator Given the text ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", describe the relation. agonist Given the text ""We found that << PSE >> inhibits interleukin-2 ([[ IL-2 ]]) and tumor necrosis factor (TNF) alpha-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line."", describe the relation. indirect-downregulator Given the text ""We previously employed a chemical genomic strategy to identify a novel small molecule, << MAC13243 >>, as a likely inhibitor of the bacterial lipoprotein targeting chaperone, [[ LolA ]]."", describe the relation. inhibitor Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal << NGF >>, BDNF and ChAT that was eliminated by [[ olanzapine ]] treatment."", describe the relation. indirect-upregulator Given the text ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (<< 5-FU >>) by [[ thymidine phosphorylase ]] (TP) inside target tissues."", describe the relation. product-of Given the text ""Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both << cAMP >> and cGMP ([[ PDE10A ]])."", describe the relation. substrate Given the text ""Low levels of << serotonin >> may reduce the density of the serotonin transporter ([[ SERT ]]) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response""."", describe the relation. downregulator Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of [[ apoptosis signal-regulating kinase 1 ]], c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α."", describe the relation. activator Given the text ""Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as GluN1/GluN2B [[ N-Methyl-D-aspartate Receptor ]] Antagonists."", describe the relation. antagonist Given the text ""Cells propagated in medium containing N5-methyltetrahydrofolate and << homocysteine >> showed a substantial increase in [[ MS ]] activity which paralleled the increase in the intracellular concentration of Me-Cbl and the Cbl bound to the enzyme."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 136,"Regarding ""Taken together, our results suggested that << Rg1 >> protected against Aβ25-35-induced apoptosis at least in part by two complementary GR-dependent ERK phosphorylation pathways: (1) down-regulating [[ HIF-1α ]] initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades."", can you determine the relation? indirect-downregulator Regarding ""The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, [[ glutamate synthase ]], and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings."", can you determine the relation? downregulator Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS)."", can you determine the relation? product-of Regarding ""Inhibition studies revealed that the << multidrug resistance-associated proteins >> (ABCCs) are involved in the transport of [[ BPDE glutathione ]] conjugates."", can you determine the relation? substrate Regarding ""The effect of troglitazone on ENT1 was PPAR(gamma)-independent and kinetic studies revealed that << troglitazone >> was a competitive inhibitor of [[ ENT1 ]]."", can you determine the relation? inhibitor Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""Discovery of novel cannabinoid receptor ligands by a virtual screening approach: further development of << 2,4,6-trisubstituted 1,3,5-triazines >> as [[ CB2 ]] agonists."", can you determine the relation? agonist Regarding ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", can you determine the relation? agonist-activator Regarding ""RESULTS: << Indomethacin >>, in vitro and in vivo. induces an increase in erythorcyte CA I and [[ CA II ]] activity."", can you determine the relation? activator Regarding ""It has been reported that oligomeric << procyanidins >> of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and [[ insulin ]]-potentiating activities."", can you determine the relation? upregulator Regarding ""Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (<< NK-1R >>), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells."", can you determine the relation? indirect-upregulator Regarding ""Derivatives of << 5-(dipentylamino)-5-oxo-pentanoic acid >> are a new class of non-peptide cholecystokinin ([[ CCK ]]) antagonists."", can you determine the relation? antagonist Regarding ""To study the mechanism underlying this phenomenon, the effects of the nonselective << beta-adrenoceptor >> antagonists propranolol [no intrinsic sympathomimetic activity (ISA)], alprenolol (weak ISA) and [[ mepindolol ]] (strong ISA) on lymphocyte beta 2-adrenoceptor density--assessed by (+/-)-[125I]-iodocyanopindolol (ICYP) binding--and plasma renin activity (PRA) were investigated in male healthy volunteers aged 23-35 years."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 137,"To determine whether 3,4-methylenedioxymethamphetamine (<< MDMA >>)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured. what is the relation? downregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator << DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). what is the relation? upregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of The studies with dThyd rescue from << cyclin E >>-cdk2 protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance. what is the relation? indirect-upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor These results confirm the selective << mGlu2 >> agonist and mGlu3 antagonist actions of [[ LY541850 ]]. what is the relation? agonist These results suggest that << HSD11B1 >>-derived [[ cortisol ]] mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep. what is the relation? product-of << Catalpol >> reduced the expression of pro-inflammatory mediates, such as [[ monocyte chemotactic protein-1 ]] (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE). what is the relation? indirect-downregulator The selective GluR5 kainate receptor agonist ATPA induces spontaneous epileptiform bursting that is sensitive to the << GluR5 >> kainate receptor antagonist [[ LY293558 ]]. what is the relation? antagonist In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of << ethylmorphine-N-demethylase >> and aniline 4-hydroxylase activity and cytochrome P450, compared to the [[ CCl4 ]] only group. what is the relation? activator Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, << 4-methoxy-2-naphthylamide >> of L-leucine for [[ leucine aminopeptidase ]], 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B. what is the relation? substrate We also observed that << fisetin >> efficiently suppressed the phosphorylation of [[ Akt ]], S6K1 and mTORC1 in adipose tissue. what is the relation? inhibitor Induction of << AhR >> by [[ TCDD ]] and prochloraz resulted in a time- and dose-dependent increase of ABCG2 gene expression and transporter protein levels. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",6,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",upregulator 138,"Consider the text ""<< Amiloride >> is a specific inhibitor of [[ uPA ]] but does not inhibit tPA."". Can you identify the relation? inhibitor Consider the text ""In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of << WIN 55,212 >> antagonized by the [[ CB2 ]] antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]."". Can you identify the relation? agonist Consider the text ""The << calcium >> homeostasis proteins [[ sarcoendoplasmic reticulum ATPase 2a ]] (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation."". Can you identify the relation? substrate Consider the text ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."". Can you identify the relation? downregulator Consider the text ""In this study, we found that << 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase ([[ iNOS ]]) in BV2 microglia."". Can you identify the relation? indirect-downregulator Consider the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""Upon treatment of isolated hepatocytes with Hb alone or in the presence of << TCDD >>, there was an increase in the [[ AhR ]]-dependent luciferase activity."". Can you identify the relation? indirect-upregulator Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates tuberin and activates [[ mTOR ]]."". Can you identify the relation? activator Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53."". Can you identify the relation? upregulator Consider the text ""<< COX-1 >> inhibition was measured as percentage inhibition of serum [[ TXB2 ]] generation in clotting whole blood, and as closure time with use of the platelet function analyser PFA-100."". Can you identify the relation? product-of Consider the text ""Derivatives of << 5-(dipentylamino)-5-oxo-pentanoic acid >> are a new class of non-peptide [[ cholecystokinin ]] (CCK) antagonists."". Can you identify the relation? antagonist Consider the text ""<< Metformin >> treatment is also associated with lower circulating levels of the orexigenic hormone [[ ghrelin ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 139,"Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular tyrosine kinase BCR-[[ ABL ]] and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS. Question: what is the relation? Answer: inhibitor The CYP3A4 activity could be induced 2-fold by << rifampicin >>, whereas [[ CYP2C9 ]] activity remained equally high. Question: what is the relation? Answer: activator The purified human enzyme also does not oxidize eight representative antitumor polyamine analogues; however, specific oligamine analogues were found to be potent inhibitors of the oxidation of << spermine >> by [[ PAOh1 ]]/SMO. Question: what is the relation? Answer: substrate Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Coexpression of GRK2 or GRK2 and arrestin-2 permitted << etorphine >> to induce down-regulation of the [[ hkor ]], although expression of arrestin-2 or dynamin I alone did not. Question: what is the relation? Answer: downregulator << Statins >> increase p21 through inhibition of histone deacetylase activity and release of promoter-associated [[ HDAC1/2 ]]. Question: what is the relation? Answer: upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Question: what is the relation? Answer: agonist-activator As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to [[ metformin ]] or pioglitazone and was noninferior to glipizide when added to metformin. Question: what is the relation? Answer: indirect-upregulator In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase ([[ LDH ]]), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system. Question: what is the relation? Answer: indirect-downregulator The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure. Question: what is the relation? Answer: agonist These results confirm the selective mGlu2 agonist and << mGlu3 >> antagonist actions of [[ LY541850 ]]. Question: what is the relation? Answer: antagonist When cultured in liquid minimal medium, yeast cells expressing the mutated << gamma-glutamyl kinase >> were found to accumulate intracellular [[ L-proline ]] and showed a prominent increase in cell viability after freezing at -20 degrees C compared to the viability of cells harboring the wild-type PRO1 gene. Question: what is the relation? Answer: product-of Treatment with EVn-50 or << VB1 >> resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of Cdk1 at Tyr15, expression of [[ cyclin B1 ]], and decreased expression of Cdc25c. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 140,"BACKGROUND: << Histamine >> synthesized by histidine decarboxylase ([[ HDC ]]) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity. what is the relation? product-of Central << 5-HT3 >> receptor stimulation by [[ m-CPBG ]] increases blood glucose in rats. what is the relation? activator INTRODUCTION: In this study, we examined the effects of the << alpha-glucosidase >> inhibitors acarbose and [[ voglibose ]] on postprandial plasma glucose and serum triglyceride levels in patients with type 2 diabetes mellitus. what is the relation? inhibitor Polyclonal antisera to either << b5R >> or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl ([[ NHOH-4-ABP ]]) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP). what is the relation? substrate RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. what is the relation? agonist-activator Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats. what is the relation? upregulator << P2Y(2) receptor >> agonist [[ INS37217 ]] enhances functional recovery after detachment caused by subretinal injection in normal and rds mice. what is the relation? agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and [[ Rspo3 ]]) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. what is the relation? downregulator Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(WAF1/<< CIP1 >>) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2. what is the relation? indirect-upregulator Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that << 5HHMF >> downregulated [[ iNOS ]] expression by suppressing NF-κB activity. what is the relation? indirect-downregulator Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors. what is the relation? antagonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor << Desipramine >> treatment decreases 3H-nisoxetine binding and [[ norepinephrine transporter ]] mRNA in SK-N-SHSY5Y cells. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 141,"Question: What is the relation in the sentence ""We have shown that << COX-2 >> mediates acid-induced [[ PGE2 ]] production.""? product-of Question: What is the relation in the sentence ""INTRODUCTION: In this study, we examined the effects of the << alpha-glucosidase >> inhibitors acarbose and voglibose on postprandial plasma [[ glucose ]] and serum triglyceride levels in patients with type 2 diabetes mellitus.""? inhibitor Question: What is the relation in the sentence ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased [[ catalase ]] (CAT) activity compared with the control.""? upregulator Question: What is the relation in the sentence ""<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase ([[ AADC ]]) and catechol-O-methyltransferase (COMT).""? substrate Question: What is the relation in the sentence ""Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (<< TCDD >>), the most potent activator of [[ AhR ]].""? activator Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity.""? agonist-activator Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Furthermore, V(5+) significantly inhibited the << TCDD >>-induced [[ AhR ]]-dependent luciferase activity.""? indirect-upregulator Question: What is the relation in the sentence ""Derivatives of << 5-(dipentylamino)-5-oxo-pentanoic acid >> are a new class of non-peptide [[ cholecystokinin ]] (CCK) antagonists.""? antagonist Question: What is the relation in the sentence ""After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist [[ 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium ]] (McN-A-343) and histamine.""? agonist Question: What is the relation in the sentence ""<< Prostacyclin >> analogues inhibit [[ tissue factor ]] expression in the human monocytic cell line THP-1 via a cyclic AMP-dependent mechanism.""? indirect-downregulator Question: What is the relation in the sentence ""<< HSYA >> treatment also decreased NF-κB [[ p65 ]] nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK).""? downregulator Question: What is the relation in the sentence ""Using the << alpha 1-adrenoceptor >> subtype-selective antagonists chlorethylclonidine (CEC), WB4101, and [[ 5-methyl-urapidil ]], we have examined the possible heterogeneity in the alpha 1-adrenoceptor populations in rabbit aorta.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 142,"Regarding ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and [[ hydrogen peroxide ]]) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."", can you determine the relation? activator Regarding ""The estrogenic agent << 3 beta,5 alpha-NET >> and estradiol at a dose of 1.0 mg also inhibited the [[ UG ]] gene expression induced by P4."", can you determine the relation? indirect-downregulator Regarding ""A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, << quercetin >>, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1)."", can you determine the relation? inhibitor Regarding ""Identification of a novel << benzimidazole >> derivative as a highly potent [[ NPY Y5 receptor ]] antagonist with an anti-obesity profile."", can you determine the relation? antagonist Regarding ""Although a proton-stimulated uptake of << cefadroxil >> was demonstrated in [[ PEPT2 ]](+/+) mice (pH 6.5 versus pH 7.4; p < 0.01), no pH dependence was observed in PEPT2(-/-) mice."", can you determine the relation? substrate Regarding ""These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and << oxymetazoline >>-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates."", can you determine the relation? agonist Regarding ""<< Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting [[ alcohols ]], amines, and thiols, respectively."", can you determine the relation? product-of Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, << beta catenin >> and mutant p53 protein expression in the [[ parathion ]]-treated cells."", can you determine the relation? indirect-upregulator Regarding ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", can you determine the relation? upregulator Regarding ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", can you determine the relation? agonist-activator Regarding ""Low levels of << serotonin >> may reduce the density of the [[ serotonin transporter ]] (SERT) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response""."", can you determine the relation? downregulator Regarding ""Agents which have recently been shown to block << cyclin D1 >> translation by regulating calcium levels are the [[ unsaturated essential fatty acid ]], eicosapentaenoic acid (EPA), the antidiabetic thiazolidinediones, and the antifungal agent, clotrimazole."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 143,"Regarding the sentence ""The folding rate for wild-type << RNase A >> is faster in the presence of the inhibitor [[ 2'CMP ]] than in its absence, indicating that the transition-state structure in the rate-determining step is stabilized by 2'CMP."", what is the relation? inhibitor Regarding the sentence ""In membranes from HEK293 cells transfected with << alpha2-receptors >>, etomidate inhibited binding of the alpha2-antagonist, [[ [3H]RX821002 ]], with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm)."", what is the relation? antagonist Regarding the sentence ""Similar to << gemfibrozil >>, clofibrate, another fibrate drug, also inhibited the expression of [[ iNOS ]]."", what is the relation? indirect-downregulator Regarding the sentence ""In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of << serotonin >> with transport-ready conformations of [[ SERT ]] when concentrations of serotonin were low and rate limiting."", what is the relation? substrate Regarding the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using dexamethasone 21-phosphate ([[ DEX-P ]]) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively."", what is the relation? activator Regarding the sentence ""These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by [[ SP ]]-NK-1R related pathway in mouse pancreatic acinar cells."", what is the relation? product-of Regarding the sentence ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."", what is the relation? upregulator Regarding the sentence ""Expression of the dominant negative mutants rab5A-N133I or rab7-<< N125I >> blunted [[ U50,488H ]]-induced down-regulation."", what is the relation? downregulator Regarding the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator Regarding the sentence ""Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by [[ TDI ]] in TDI-sensitized rats."", what is the relation? indirect-upregulator Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist [[ acetylcholine ]] (ACh) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump."", what is the relation? agonist Regarding the sentence ""<< Simvastatin >>, an HMG-CoA reductase inhibitor with mild inhibition of LFA-1, induced the production of [[ interleukin (IL)-18 ]], tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in human peripheral blood mononuclear cells (PBMC)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 144,"One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Please explain the relation. substrate_product-of Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in [[ ERK1/2 ]] and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR. Please explain the relation. upregulator BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, << EC 4.1.1.15 >>) catalyses the conversion of glutamate to gamma-aminobutyric acid ([[ GABA ]]). Please explain the relation. product-of RESULTS: Following administration of the highest of the << GAL >> doses used (2.5; 5; 10 mg/kg i.m.), [[ AChE ]] activity decreased mainly in the frontal cortex, hippocampus and hypophysis. Please explain the relation. inhibitor PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases ([[ COX ]]) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). Please explain the relation. substrate Subsequent analysis revealed that << cucurbitacin I >> strongly activates [[ RhoA ]] and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers. Please explain the relation. activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin. Please explain the relation. downregulator In mechanistic studies, << Silibinin >> decreased the protein level of [[ p34cdc2 ]], which might be the possible molecular mechanism of Silibinin efficacy on the growth inhibition in SGC-7901 cells. Please explain the relation. indirect-downregulator METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist (SB-207266) on the [[ cisapride ]] mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects. Please explain the relation. agonist The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Please explain the relation. agonist-activator In the present study, we compared the pharmacology of (+/-)pindolol, WAY-100635 (a 5-HT(1A) antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and << isamoltane >> (a [[ 5-HT(1B) ]] antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. Please explain the relation. antagonist Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Please explain the relation. indirect-upregulator By contrast, << 11beta-HSD2 >> plays a pivotal role in aldosterone target tissues where it catalyses the opposite reaction (i.e. inactivation of cortisol to [[ cortisone ]]) to prevent activation of the mineralocorticoid receptor (MR) by cortisol. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 145,"In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (<< 5HHMF >>) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase ([[ iNOS ]]) in BV2 microglia. Query: What is the relation? indirect-downregulator In addition, << 5HHMF >> blocked LPS-induced phosphorylation of [[ IκB ]], resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression. Query: What is the relation? inhibitor << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS). Query: What is the relation? product-of Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Query: What is the relation? upregulator The values of mean corpuscular hemoglobin concentration and mean corpuscular << hemoglobin >> increased in the [[ STX ]] group. Query: What is the relation? indirect-upregulator Leukotriene A(4) hydrolase (<< LTA(4)H >>) is a cystolic enzyme that stereospecifically catalyzes the transformation of [[ LTA(4) ]] to LTB(4). Query: What is the relation? substrate Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]. Query: What is the relation? downregulator In a recent study using protein-specific anti-acetyl lysine antibodies and immunological methods, we demonstrated the ability of << aspirin >> to acetylate the [[ tumor suppressor protein p53 ]]. Query: What is the relation? activator alpha(1)-Adrenoceptor antagonists were tested against the << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach. Query: What is the relation? agonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. Query: What is the relation? antagonist In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Query: What is the relation? agonist-activator Upon << nicotine >> pre-exposure, brain acetylcholinesterase increased, while monoamine oxidase ([[ MAO ]]) decreased. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 146,"Regarding the sentence ""These unexpected and intriguing complexities seem likely to have some as yet undefined role in regulating << SSAT >> activity or stability as a part of [[ polyamine ]] homeostasis."", what is the relation? product-of Regarding the sentence ""Liver << BHMT >> activity was 1.3-fold higher in rats fed the Met deficient diet containing [[ choline ]], which was reflected in corresponding increases in mRNA content and immunodetectable protein."", what is the relation? indirect-upregulator Regarding the sentence ""They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of arginine with rhArg, to citrulline, which is converted back to << arginine >> via [[ ASS ]]."", what is the relation? substrate Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""<< Prostacyclin >> analogues inhibit [[ tissue factor ]] expression in the human monocytic cell line THP-1 via a cyclic AMP-dependent mechanism."", what is the relation? indirect-downregulator Regarding the sentence ""The selective << beta1AR >> antagonists atenolol and metoprolol blocked [[ isoproterenol ]]-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively."", what is the relation? agonist Regarding the sentence ""The << 5-HT(2B/2C)-receptor >> antagonist [[ SB 206553 ]] facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect."", what is the relation? antagonist Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""<< ABT-199 >>, a potent and selective [[ BCL-2 ]] inhibitor, achieves antitumor activity while sparing platelets."", what is the relation? inhibitor Regarding the sentence ""In addition, << cobalt protoporphyrin >> (CoPP), a specific [[ HO-1 ]] inducer, predominantly suppressed LPS-induced NO production."", what is the relation? activator Regarding the sentence ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."", what is the relation? upregulator Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced << NADPH oxidase >> activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by [[ resveratrol ]]."", what is the relation? downregulator Regarding the sentence ""Blood pressure was increased in rats exposed to IH, and treatment with the << PDK-1 >> inhibitor OSU-03012 [[[ 2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl}-acetamide ]]] (33 mg/day) lowered blood pressure in IH but not sham group rats."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 147,"Regarding ""Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin ([[ TCDD ]]), the most potent activator of AhR."", can you determine the relation? upregulator Regarding ""Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS."", can you determine the relation? product-of Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""Tissue-type plasminogen activator (tPA), a << serine >> protease well known for generating [[ plasmin ]], has been demonstrated to induce matrix metalloproteinase-9 (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts."", can you determine the relation? indirect-upregulator Regarding ""Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing NF-κB activity and induction of [[ Nrf2 ]]-dependent HO-1 activity."", can you determine the relation? downregulator Regarding ""<< Kynurenic acid >> (KA) is an endogenous glutamate receptor antagonist at the level of the different [[ ionotropic glutamate receptors ]]."", can you determine the relation? antagonist Regarding ""INTRODUCTION: In this study, we examined the effects of the << alpha-glucosidase >> inhibitors [[ acarbose ]] and voglibose on postprandial plasma glucose and serum triglyceride levels in patients with type 2 diabetes mellitus."", can you determine the relation? inhibitor Regarding ""The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition."", can you determine the relation? agonist Regarding ""Density functional theory calculations using the hybrid functional B3LYP have been performed to study the << methyl >> transfer step in [[ glycine N-methyltransferase ]] (GNMT)."", can you determine the relation? substrate Regarding ""Inhibition of human iNOS promoter-driven luciferase activity by << gemfibrozil >> in cytokine-stimulated U373MG astroglial cells suggests that this compound inhibits the transcription of [[ iNOS ]]."", can you determine the relation? indirect-downregulator Regarding ""In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives ([[ AA-861 ]], tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines."", can you determine the relation? activator Regarding ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", can you determine the relation? agonist-activator Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""INTRODUCTION: << Medroxyprogesterone acetate >> (MPA) induces estrogen receptor ([[ ER ]])-positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",6,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",upregulator 148,"Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells. Query: What is the relation? upregulator To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, sodium hydrosulphide (<< NaHS >>), (10, 50 and 100 muM), that resulted in a significant increase in SP concentration and expression of [[ PPT-A ]] and NK1-R in acinar cells. Query: What is the relation? indirect-upregulator The results reinforce previous assumptions that << dopamine >> may interact with eicosanoid metabolism by means of [[ D(2) receptor ]] activation, and implicate an involvement of cPLA(2) and COX-2 in this effect. Query: What is the relation? activator However, a lower concentration of << dipyridamole >> (3 microM) that blocks PDE9, [[ PDE10 ]], and PDE11, but not PDE8, did not inhibit ecto-phosphodiesterase activity. Query: What is the relation? inhibitor OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting << alpha2 adrenergic receptor >> (AR) agonist ([[ dexmedetomidine ]]). Query: What is the relation? agonist << Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS). Query: What is the relation? product-of Inhibition of endogenous production of << H(2)S >> by PAG significantly suppressed [[ SP ]] concentration, PPT-A expression and NK1-R expression in the acini. Query: What is the relation? indirect-downregulator RESULTS: (+/-)-, R-, and S-modafinil bind to the << DAT >> and inhibit [[ DA ]] uptake less potently than cocaine, with R-modafinil having approximately threefold higher affinity than its S-enantiomer. Query: What is the relation? substrate Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase ([[ SOD ]]) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. Query: What is the relation? downregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the << 5-HT(1A/1B)-receptor >> antagonist [[ (-)-propranolol ]] and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it. Query: What is the relation? antagonist Here, we characterized the target profile of the dual SRC/<< ABL >> inhibitor [[ bosutinib ]] employing a two-tiered approach using chemical proteomics to identify natural binders in whole cell lysates of primary CML and K562 cells in parallel to in vitro kinase assays against a large recombinant kinase panel. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 149,"Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and [[ Rspo3 ]]) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. what is the relation? downregulator An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (<< SCH 900229 >>), a potent, [[ PS1 ]]-selective γ-secretase inhibitor and clinical candidate for the treatment of Alzheimer's disease. what is the relation? inhibitor << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of << Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting [[ alcohols ]], amines, and thiols, respectively. what is the relation? product-of Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and [[ JNK1/2 ]] activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR. what is the relation? upregulator The ARB << eprosartan >> is a nonbiphenyl nontetrazole [[ angiotensin II type 1 receptor ]] (AT1) antagonist, which acts to decrease total peripheral resistance. what is the relation? antagonist Additionally, << MPTP >> significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in [[ Bax ]] expression, cytochrome C translocation to the cytosol, andcleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment. what is the relation? indirect-upregulator UGT1A6 exhibited a significantly higher Vmax and Km values toward both << HFC >> and UDP-glucuronic acid than the other [[ UGTs ]]. what is the relation? substrate Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], [[ AM2389 ]] [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia. what is the relation? agonist Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, [[ cyclin D1 ]], MMP7, and c-Myc. what is the relation? indirect-downregulator The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. what is the relation? agonist-activator << Cortisol >> and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial [[ PTGS2 ]] activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium. what is the relation? activator SDH (L-serine dehydratase, << EC 4.3.1.17 >>) catalyzes the pyridoxal 5'-phosphate (PLP)-dependent dehydration of L-serine to yield [[ pyruvate ]] and ammonia. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 150,"Given the text ""Pharmacological properties of << lorglumide >> as a member of a new class of [[ cholecystokinin ]] antagonists."", describe the relation. antagonist Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""Introduction: 5-Lipoxygenase (<< 5-LO >>) is a crucial enzyme of the [[ arachidonic acid ]] (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) with the help of FLAP, the 5-LO-activating protein."", describe the relation. substrate Given the text ""<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive [[ oxygen ]] species (ROS), which are capable of initiating and promoting carcinogenesis."", describe the relation. product-of Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", describe the relation. agonist-activator Given the text ""<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, [[ glycosylated hemoglobin ]] (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin."", describe the relation. indirect-downregulator Given the text ""The identification of the << succinate receptor >> SUCNR1 in platelets is of particular interest, because physiologically relevant concentrations of [[ succinate ]] were shown to potentiate the effect of low doses of a variety of platelet agonists."", describe the relation. agonist Given the text ""Some of these derivatives showed good inhibitory potency against two human CA isozymes involved in important physiological processes, CA I, and << CA II >>, of the same order of magnitude as the clinically used drugs acetazolamide and [[ methazolamide ]]."", describe the relation. inhibitor Given the text ""Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of [[ VEGF ]] and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells."", describe the relation. downregulator Given the text ""In PFC, << DEX >> caused activation of [[ AKT ]], augmentation of pro-survival Bcl-2 protein and enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to mitochondria."", describe the relation. activator Given the text ""In PFC, << DEX >> caused activation of AKT, augmentation of pro-survival [[ Bcl-2 ]] protein and enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to mitochondria."", describe the relation. indirect-upregulator Given the text ""Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity."", describe the relation. upregulator Given the text ""<< Haloperidol >> promotes mTORC1-dependent phosphorylation of ribosomal protein S6 via dopamine- and cAMP-regulated phosphoprotein of 32 kDa and inhibition of [[ protein phosphatase-1 ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 151,"<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, IL-18, << IL-17A >> and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]]. Query: What is the relation? indirect-downregulator Tissue-type plasminogen activator (tPA), a << serine >> protease well known for generating plasmin, has been demonstrated to induce [[ matrix metalloproteinase-9 ]] (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts. Query: What is the relation? indirect-upregulator << CYP1A1 >> and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Query: What is the relation? upregulator The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine ]] (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described. Query: What is the relation? inhibitor Subsequent analysis revealed that << cucurbitacin I >> strongly activates RhoA and the Rho effector [[ Rho kinase ]] (ROCK) in breast cancer cells and induces the formation of stress fibers. Query: What is the relation? activator After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full << muscarinic receptor >> agonist [[ methacholine ]], the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine. Query: What is the relation? agonist During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and << cortisol >> via hydroxysteroid (11-β) dehydrogenase 1 ([[ HSD11B1 ]]). Query: What is the relation? product-of Expression of the dominant negative mutants << rab5A >>-N133I or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation. Query: What is the relation? downregulator In the reverse case, mutation of the orthologous glycine (Gly553) to methionine in << carnitine octanoyltransferase >> (COT) decreased activity toward its natural substrates, medium- and long-chain [[ acyl-CoAs ]], and increased activity toward short-chain acyl-CoAs. Query: What is the relation? substrate RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Query: What is the relation? agonist-activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor The anti-hyperthermic effect of Lu AF21934 (5 mg/kg) in the SIH test was inhibited by the << benzodiazepine receptor >> antagonist [[ flumazenil ]] (10 mg/kg) and was not serotonin-dependent, as it persisted in serotonin-deficient mice and upon blockade of either 5-HT(1A) receptors by WAY100635, or 5-HT(2A/2C) receptors by ritanserin. Query: What is the relation? antagonist In the study reported here, the effects of acute PLZ treatment on the levels of various << amino acids >>, some of which are also metabolized by [[ pyridoxal phosphate-dependent transaminases ]] were compared in rat whole brain. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 152,"Purified << PAOh1 >>/SMO oxidizes both spermine (K(m)=1.6 microM) and [[ N(1)-acetylspermine ]] (K(m)=51 microM), but does not oxidize spermidine. Query: What is the relation? substrate << Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity. Query: What is the relation? upregulator In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the [[ methyl CpG-binding proteins ]] (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Query: What is the relation? downregulator In contrast, there was little change in mRNA levels for << GTP cyclohydrolase I >> (GTPCH), the rate limiting enzyme in synthesis of the tetrahydrobiopterin ([[ BH4 ]]), the obligate cofactor for TPH. Query: What is the relation? product-of Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the [[ incretin hormones ]] glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Query: What is the relation? indirect-upregulator Although the inhibition of << cyclooxygenases >> by [[ aspirin ]], which leads to its anti-inflammatory/analgesic properties, has been well studied, the mechanisms involved in its chemopreventive effects as well as some of its adverse effects are as yet ill-defined. Query: What is the relation? inhibitor OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a [[ peroxisome proliferator-activated receptor alpha ]] (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent. Query: What is the relation? agonist Nizatidine (<< LY139037 >>), a selective [[ histamine H2-receptor ]] antagonist, is a potent inhibitor of gastric acid secretion. Query: What is the relation? antagonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of Furthermore, << PTE >> treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of [[ STAT3 ]]. Query: What is the relation? indirect-downregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator Since << gemfibrozil >> is known to activate peroxisome proliferator-activated receptor-alpha ([[ PPAR-alpha ]]), we investigated the role of PPAR-alpha in gemfibrozil-mediated inhibition of iNOS. Query: What is the relation? activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor Investigation of bradykinin metabolism in human and rat plasma in the presence of the dual << ACE >>/NEP inhibitors GW660511X and [[ omapatrilat ]]. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 153,"Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator 6-DHSG was metabolised by GSH to form a GSH conjugate (<< GS-6-DHSG >>) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of [[ glutathione-S-transferase ]] (GST). Please explain the relation. product-of Taken together, the data provide evidence that the synergistic antiproliferative effect of << resveratrol >> and clofarabine is linked to the inhibition of [[ Akt ]] and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma. Please explain the relation. inhibitor Suppression of << Src >>/ERK and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells. Please explain the relation. downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Please explain the relation. substrate_product-of These effects were fully counteracted by dietary << phenolics >> which inhibited ROS overproduction and GSH consumption, rendered the reactive transcription of glutathione-associated enzymes unnecessary and blocked the intracellular signals leading to the overexpression and rearrangement of [[ p66Shc ]] signalling molecule. Please explain the relation. indirect-downregulator << Alprenolol >> and bromoacetylalprenololmenthane are competitive slowly reversible antagonists at the [[ beta 1-adrenoceptors ]] of rat left atria. Please explain the relation. antagonist Effect of << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity on contractile receptor function in airway smooth muscle. Please explain the relation. activator The protein exhibited modest H(2)O(2)-dependent << peroxidase >> activities with guaiacol, [[ potassium iodide ]], and 2,2(')-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS). Please explain the relation. substrate Effect of << ramelteon >> (TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor performance in mice. Please explain the relation. agonist The values of mean corpuscular << hemoglobin >> concentration and mean corpuscular hemoglobin increased in the [[ STX ]] group. Please explain the relation. indirect-upregulator CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme. Please explain the relation. upregulator Hydrogen sulfide (<< H(2)S >>), a regulatory gaseous molecule that is endogenously synthesized by cystathionine gamma-lyase (CSE) and/or [[ cystathionine beta-synthase ]] (CBS) from L-cysteine (L-Cys) metabolism, is a putative vasodilator, and its role in nitric oxide (NO) production is unexplored. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 154,"Consider the text ""We evaluated the effect of << anastrozole >>, a more selective [[ aromatase ]] inhibitor, on the hormonal and semen profiles of infertile men with abnormal baseline testosterone-to-estradiol ratios."". Can you identify the relation? inhibitor Consider the text ""In contrast, the << D-1997 >>-induced responses were potently and concentration-dependently antagonized by the mixed [[ 5-HT1-like ]] and 5-HT2 receptor antagonist methiothepin (0.01-1 microM)."". Can you identify the relation? agonist Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""The ratio between the GDC/<< SHMT >> and C1-THF synthase/SHMT pathways of [[ Ser ]] synthesis from [alpha-(13)C]Gly and [(13)C]formate, respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1."". Can you identify the relation? product-of Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."". Can you identify the relation? agonist-activator Consider the text ""In human blood, the tested glucocorticoids << beclomethasone >>, dexamethasone and fluticasone inhibited the LPS induced [[ TNF ]] release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced TNF release, with the exception of dexamethasone, was much less pronounced."". Can you identify the relation? indirect-downregulator Consider the text ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and << AH 6809 >> (EP1 and [[ EP2 ]] specific)."". Can you identify the relation? antagonist Consider the text ""These results indicate that << phenobarbital >> treatment induces [[ KCNK1 ]] to elicit a male-specific and growth-suppressing signal."". Can you identify the relation? activator Consider the text ""Apoptosis studies (DAPI staining and << caspase 3 >> activity) showed a marked increase in the presence of [[ MXF ]] and VP-16 compared to VP-16 alone."". Can you identify the relation? indirect-upregulator Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h."". Can you identify the relation? upregulator Consider the text ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, << 4-methoxy-2-naphthylamide >> of L-glutamic acid for [[ aminopeptidase A ]] and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B."". Can you identify the relation? substrate Consider the text ""Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of [[ CA I ]] and CA II."". Can you identify the relation? downregulator Consider the text ""With respect to the substrate << dihydroorotate >>, atovaquone was an uncompetitive inhibitor of [[ human dihydroorotate dehydrogenase ]] (Kiu = 11.6 microM) and a non-competitive inhibitor of the rat enzyme (Kiu = 905/ Kic = 1,012 nM)."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 155,"Regarding ""<< 2-(2-Aminoethyl)-quinoline >> (D-1997): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", can you determine the relation? agonist Regarding ""The potency of the selective << alpha 1D-adrenoceptor >> antagonist [[ BMY 7378 ]] against noradrenaline (pA2 = 6.16 +/- 0.13) and of the selective alpha 1A-adrenoceptor antagonist RS-17053 against noradrenaline (pKB = 8.35 +/- 0.10) and against the selective alpha 1A-adrenoceptor agonist A-61603 (pKB = 8.40 +/- 0.09) were too low to account for alpha 1D- and alpha 1A-adrenoceptor involvement."", can you determine the relation? antagonist Regarding ""Expression of the dominant negative mutants arrestin-2(319-418) or dynamin I-K44A significantly reduced << U50,488H >>-induced down-regulation of the [[ hkor ]]."", can you determine the relation? downregulator Regarding ""RESULTS: Both << PLZ >> and VIG inhibited [[ GABA-T ]] and elevated GABA levels."", can you determine the relation? inhibitor Regarding ""Luciferase reporter assays showed that transcription of << FDX1 >> was synergistically activated by the NR5A family and [[ 8Br-cAMP ]] treatment through two SF-1 binding sites and a CRE-like sequence in a human ovarian granulosa cell line, KGN."", can you determine the relation? indirect-upregulator Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS)."", can you determine the relation? product-of Regarding ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Interestingly, part of << MCT2 >> immunoreactivity is located at postsynaptic sites, suggesting a particular role of [[ monocarboxylates ]] and their transporters in synaptic transmission."", can you determine the relation? substrate Regarding ""Similar to << gemfibrozil >>, clofibrate, another fibrate drug, also inhibited the expression of [[ iNOS ]]."", can you determine the relation? indirect-downregulator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", can you determine the relation? agonist-activator Regarding ""<< 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on [[ AMPK ]] consensus sites but did not change the amount of TSC1 bound to TSC2."", can you determine the relation? activator Regarding ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and << activating protein-1 >>, which were increased in [[ fructose ]]-fed rats."", can you determine the relation? upregulator Regarding ""<< Puerarin >> stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and PI3K/[[ Akt ]] activation."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 156,"Methionine synthase reductase (<< MTRR >>) is an enzyme involved in the conversion of [[ Hcy ]] to methionine. Please explain the relation. substrate Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin. Please explain the relation. downregulator Evidence has accumulated in the last few years that the expression of the << microsomal/peroxidase antigen >> (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis. Please explain the relation. upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists. Please explain the relation. antagonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Please explain the relation. substrate_product-of Methionine synthase reductase (<< MTRR >>) is an enzyme involved in the conversion of Hcy to [[ methionine ]]. Please explain the relation. product-of In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator Moreover, use of the pharmacological << AMP-activated protein kinase >> (AMPK) inhibitor [[ compound C ]] revealed that AMPK is essential for suppressing SREBP-1c expression in phillyrin-treated cells. Please explain the relation. inhibitor In alpha2B-receptor-expressing HEK293 cells, << etomidate >> rapidly increased phosphorylation of the [[ extracellular signal-related kinases ]] ERK1/2. Please explain the relation. activator The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters ([[ alanine aminotransferase ]], aspartate aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine). Please explain the relation. indirect-upregulator << Dexamethasone >> (DEX) inhibited the anti-CD3-induced production of IL-4, IL-5 and [[ IFN-gamma ]] in all 20 clones tested. Please explain the relation. indirect-downregulator Discovery of novel cannabinoid receptor ligands by a virtual screening approach: further development of << 2,4,6-trisubstituted 1,3,5-triazines >> as [[ CB2 ]] agonists. Please explain the relation. agonist << Mercury >> induces the expression of [[ cyclooxygenase-2 ]] and inducible nitric oxide synthase. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 157,"Regarding ""In this study, we examined whether << betaxolol >> and other [[ beta-adrenoceptor ]] antagonists interact directly with neurotoxin binding to sites 1 and 2 of the voltage-sensitive sodium channel (Na(+) channel) in rat cerebrocortical synaptosomes."", can you determine the relation? antagonist Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", can you determine the relation? agonist-activator Regarding ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Methods: The stability of six << acyl glucuronides >> in the presence of [[ hCES1 ]], hCES2, and buffer alone (100 mM potassium phosphate, pH 7.4, 37°C) were investigated."", can you determine the relation? substrate Regarding ""No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary [[ efflux transporters ]] BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells."", can you determine the relation? inhibitor Regarding ""A prerequisite for this hypothesis was the unproved assumption that rabbit and human << alpha(2A)-adrenoceptors >> are equally activated by [[ rilmenidine ]]."", can you determine the relation? activator Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""RESULTS: << DZN >> induced histophatological damages and elevated the level of cardiac marker [[ CK-MB ]]."", can you determine the relation? indirect-upregulator Regarding ""<< ATP-binding cassette transporter A1 >> is involved in hepatic [[ alpha-tocopherol ]] secretion."", can you determine the relation? product-of Regarding ""Dexamethasone (<< DXM >>) decreased the expression of CXCL-8, [[ VEGF ]], and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS."", can you determine the relation? indirect-downregulator Regarding ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, [[ MBD-2 ]] and MBD-3), in MEF cells by the proteasomal pathway."", can you determine the relation? downregulator Regarding ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/[[ CIP1 ]]) and p53."", can you determine the relation? upregulator Regarding ""Systemic administration of << beta2-adrenoceptor >> agonists, formoterol and [[ salmeterol ]], elicit skeletal muscle hypertrophy in rats at micromolar doses."", can you determine the relation? agonist Regarding ""Furthermore, << nobiletin >> could inhibit HGF-induced the membrane localization of phosphorylated [[ c-Met ]], ERK2, and Akt, but not phosphorylated JNK1/2 and p38."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 158,"Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""Promoter and electromobility shift assays showed that transcriptional activation of << NF-κB >> was significantly reduced by [[ catalpol ]] treatment, while AP-1 was not."". Can you identify the relation? indirect-downregulator Consider the text ""3. << CYP3A >> induction in the liver increased depending on the dose of [[ DEX-P ]], whereas that in intestine showed a mild increase, but the induction level was almost constant regardless of the dose of DEX-P."". Can you identify the relation? activator Consider the text ""These results suggest that ACS1 and << ACS4 >> may be linked to [[ triacylglycerol ]] synthesis."". Can you identify the relation? product-of Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."". Can you identify the relation? substrate_product-of Consider the text ""<< Conivaptan >> is a nonpeptide dual [[ V1a/V2 AVP receptor ]] antagonist."". Can you identify the relation? antagonist Consider the text ""In conclusion, << IL-8 >> production and neutrophil infiltration are increased in high-[[ glucose ]] environment due to elevated ROS level and contributed to impaired wound healing in diabetic skin."". Can you identify the relation? indirect-upregulator Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/[[ CIP1 ]]) and p53."". Can you identify the relation? upregulator Consider the text ""<< PIP5K1B >> encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [[[ PI(4)P ]]] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]."". Can you identify the relation? substrate Consider the text ""Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular [[ tyrosine kinase ]] BCR-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS."". Can you identify the relation? inhibitor Consider the text ""Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of CA I and [[ CA II ]]."". Can you identify the relation? downregulator Consider the text ""Prazosin (nonselective << alpha(1)-adrenoceptor >> antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively)."". Can you identify the relation? agonist Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""It was, therefore, proposed that H. pylori may in fact, antagonize, << aspirin >>-induced delay of ulcer healing due to suppression of acid secretion by the enhancement in PGE(2) possibly derived from COX-2 expression and activity and to the overexpression of growth factors such as [[ TGF alpha ]] and VEGF."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 159,"<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Query: What is the relation? agonist-activator Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity. Query: What is the relation? downregulator << Cobalt chloride >>, a typical [[ HIF ]] activator, induced the gene expression of CAR-target genes, including cyp2b9 and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver. Query: What is the relation? activator The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB ([[ NF-κB ]]) p65 and p50 subunits. Query: What is the relation? indirect-downregulator Felodipine and the << p-chloro >> analogue inhibited the basal (Ca2+/calmodulin-independent) activity of [[ cAMP phosphodiesterase ]] as well as the calmodulin-stimulated activity. Query: What is the relation? inhibitor << Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of [[ polyamine ]] levels in human cells, as acetylation of spermidine and spermine triggers export or degradation. Query: What is the relation? product-of << Betaxolol >>, a beta(1)-adrenoceptor antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other [[ beta-adrenoceptor ]] antagonists. Query: What is the relation? antagonist << PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins ([[ Bax ]], Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. Query: What is the relation? indirect-upregulator Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in [[ ERK1/2 ]] and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR. Query: What is the relation? upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine << 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine >> (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]. Query: What is the relation? substrate OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (<< AR >>) agonist ([[ dexmedetomidine ]]). Query: What is the relation? agonist These findings are the first to show that long-term exposure to << Mn >> during a critical period of neurodevelopment causes motor coordination dysfunction with parallel increment in oxidative stress markers, p38([[ MAPK ]]) phosphorylation and caspase activity in the striatum. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 160,"<< Thalidomide >> reduced [[ COX-2 ]] expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60. what is the relation? indirect-downregulator In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, [[ DNMT-3a ]], and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. what is the relation? downregulator Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, [[ nuclear factor-kappaB ]] and activating protein-1, which were increased in fructose-fed rats. what is the relation? upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Hydrogen sulphide (H(2)S) is synthesized from << L-cysteine >> via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS). what is the relation? substrate Brain but not spinal << NR2B >> receptor is responsible for the anti-allodynic effect of an NR2B subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model. what is the relation? antagonist Consistent with the weak transactivation activity of esterified-<< BM >> mediated by [[ rat GR ]], there were few side effects, evaluated by thymus involution and body weight loss, in an antigen-induced asthmatic model in rats. what is the relation? agonist In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. what is the relation? agonist-activator The cytosine analog 5-aza-2'-deoxycytidine (<< decitabine >>) hypomethylates DNA by inhibiting [[ DNA methyltransferase ]]. what is the relation? inhibitor << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. what is the relation? substrate_product-of To this end, 158N murine oligodendrocytes were treated with 7KC or << 7βOHC >> inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and [[ caspase-3 ]] activation. what is the relation? activator << Cycloxygenase-2 >> (COX-2)-derived [[ prostaglandin E2 ]] (PGE2) has been shown to be important in esophageal tumorigenesis. what is the relation? product-of In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and [[ Bax ]] proteins. what is the relation? indirect-upregulator << Irbesartan >> (Aprovel, Avapro, Irbetan, Karvea), an [[ angiotensin II receptor type 1 ]] antagonist, is approved in many countries worldwide for the treatment of hypertension. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 161,"Question: What is the relation in the sentence ""On the other hand, high doses of okadaic acid (10 ng/mouse, i.c.v.) and << cantharidin >> (1 microg/mouse, i.c.v.), which also block [[ PP1 ]], and calyculin-A (0.1 fg/mouse-1 ng/mouse, i.c.v.), which inhibits equally both PP1 and PP2A, did not modify the morphine-induced antinociception.""? inhibitor Question: What is the relation in the sentence ""RESULTS: In drug discrimination studies, lisuride fully mimicked the << 5-HT(1A) >> agonist [[ LY 293284 ]], only partially substituted for LSD and DOI, and failed to substitute for (+)-amphetamine.""? agonist Question: What is the relation in the sentence ""<< N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase >> (EC 3.1.4.45; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome.""? product-of Question: What is the relation in the sentence ""Interestingly, << ursolic acid >> increased the phosphorylation of AMPK and [[ coenzyme A carboxylase ]] and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.""? activator Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of [[ cyclin D1 ]], cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53.""? downregulator Question: What is the relation in the sentence ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of [[ R-spondins ]] (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.""? indirect-downregulator Question: What is the relation in the sentence ""Dietary << EPA >>/DHA treatment restored endogenous biosynthesis of n-3 derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving [[ insulin ]] sensitivity.""? indirect-upregulator Question: What is the relation in the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Local LC citalopram effect was abolished by LC presence of the 5-HT3 receptor antagonist MDL72222 (1 μM) but not the << 5-HT1/2 >> receptor antagonist [[ methiothepin ]] (1 μM).""? antagonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of [[ L-serine ]] and L-threonine to yield pyruvate or 2-oxobutyrate.""? substrate Question: What is the relation in the sentence ""Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity.""? upregulator Question: What is the relation in the sentence ""In rats, << rifamycin SV >> and rifampicin were shown to interfere with hepatic organic anion uptake by inhibition of the organic anion transporting polypeptides [[ Oatp1 ]] and Oatp2.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 162,"<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Question: what is the relation? Answer: substrate_product-of Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms. Question: what is the relation? Answer: downregulator There was no significant difference in TLR4, NF-κB, and << IL-27 >> mRNA and proteins between curcumin-treated and [[ sulfasalazine ]]-treated groups. Question: what is the relation? Answer: indirect-downregulator CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Question: what is the relation? Answer: upregulator These results suggest that << HSD11B1 >>-derived [[ cortisol ]] mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep. Question: what is the relation? Answer: product-of The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, [[ TMB-4 ]] and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. Question: what is the relation? Answer: activator (+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and << RS 17053 >> appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]. Question: what is the relation? Answer: antagonist Alprenolol and BAAM also caused surmountable antagonism of << isoprenaline >> responses, and this [[ beta 1-adrenoceptor ]] antagonism was slowly reversible. Question: what is the relation? Answer: agonist Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor << manumycin A >> caused elevation of [[ ApoA-I ]] secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. Question: what is the relation? Answer: indirect-upregulator << CP-690550 >>, a [[ JAK3 ]] inhibitor is currently in phase II clinical trials.FK778, is a synthetic malononitrilamide that targets the critical enzyme of the de novo pyrimidine synthesis, dihydroorotic acid dehydrogenase, and receptor-associated tyrosine kinases has completed phase II trials. Question: what is the relation? Answer: inhibitor In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: agonist-activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor << Doxorubicin >> is mainly excreted into the bile via P-glycoprotein ([[ P-gp ]]) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily. Question: what is the relation? Answer: substrate GnRH stimulation of << CREB >> phosphorylation (pCREB) in the gonadotrope-derived LβT2 cell line was attenuated by a protein kinase A (PKA) inhibitor, [[ H89 ]]. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 163,"Question: What is the relation in the sentence ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of [[ VEGF ]]and MMP-9, resulting from the inhibition of Akt pathway.""? downregulator Question: What is the relation in the sentence ""Consumption of << alcohol >> for 8weeks induced severe liver damage with increases in prognostic indicators such as [[ aspartate transaminase ]], alanine transaminase in serum whereas co-administration of CNF suppressed their increases.""? indirect-upregulator Question: What is the relation in the sentence ""Although inhibition of << LH >> release can be achieved by [[ estrogen ]] and progestins, an optimal inhibitory effect on the prostate is obtained by the combined administration of the antiandrogen with an LHRH agonist that causes a specific blockage of testicular androgen biosynthesis as well as an inhibition of the LH responsiveness to LHRH.""? inhibitor Question: What is the relation in the sentence ""Compared pharmacological characteristics in humans of racemic << cetirizine >> and levocetirizine, two [[ histamine H1-receptor ]] antagonists.""? antagonist Question: What is the relation in the sentence ""Antiarrhythmic effects of << (-)-epicatechin-3-gallate >>, a novel [[ sodium channel ]] agonist in cultured neonatal rat ventricular myocytes.""? agonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""A prerequisite for this hypothesis was the unproved assumption that rabbit and human << alpha(2A)-adrenoceptors >> are equally activated by [[ rilmenidine ]].""? activator Question: What is the relation in the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""<< Juglone >>, isolated from Juglans mandshurica Maxim, induces apoptosis via down-regulation of [[ AR ]] expression in human prostate cancer LNCaP cells.""? indirect-downregulator Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""<< PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases (COX) and [[ prostaglandin E synthases ]] (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4).""? product-of Question: What is the relation in the sentence ""The positive correlation between << vitamin A >> and [[ immunoglobulin A ]] concentrations might be the result of the vitamin A inductive effect during immunoglobulins A synthesis.""? upregulator Question: What is the relation in the sentence ""<< Mitochondrial arginase II >> modulates nitric-oxide synthesis through nonfreely exchangeable [[ L-arginine ]] pools in human endothelial cells.""? substrate Question: What is the relation in the sentence ""These results indicate that carbetocin is a partial agonist/antagonist to the << oxytocin receptor >> while the two metabolites [[ carbetocin ]] metabolite I and carbetocin metabolite II are pure antagonists.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 164,"Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II. what is the relation? product-of << DXM >> and 1400W attenuated the mRNA expression of [[ E-selectin ]] and iNOS induced by the costimulation of reIL-4, reTNF-alpha, and LPS. what is the relation? indirect-downregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. what is the relation? upregulator Suppression of << Src >>/ERK and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells. what is the relation? downregulator These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and cdk2 [[ kinase ]] activities. what is the relation? activator Noradrenaline and << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively. what is the relation? agonist << Prazosin >> (nonselective [[ alpha(1)-adrenoceptor ]] antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively). what is the relation? antagonist Furthermore, << butein >> treatment caused nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of [[ antioxidant response elements ]] (AREs). what is the relation? indirect-upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Of the << PDE >> inhibitors tested, dipyridamole was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of [[ cAMP ]] and cGMP hydrolysis, respectively. what is the relation? substrate One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). what is the relation? substrate_product-of Although thioredoxin reductase (<< TRR >>) inhibitors ([[ aurothioglucose ]] and Sb(III)) inhibited cytosolic DMAs(V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs(V) reduction. what is the relation? inhibitor The immunomodulatory activity of << thalidomide >> has been ascribed to the selective inhibition of [[ tumor necrosis factor alpha ]] from monocytes. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 165,"Moreover, a normal level of expression of PSS1 and/or << PSS2 >> is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis. Question: what is the relation? Answer: product-of 4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >[[ UGT1A7 ]] >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs. Question: what is the relation? Answer: substrate In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor In contrast, the selective << beta2AR >> antagonists ICI-118,551 and butoxamine inhibited [[ isoproterenol ]]-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively). Question: what is the relation? Answer: agonist One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, IL-18, << IL-17A >> and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]]. Question: what is the relation? Answer: indirect-downregulator Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors. Question: what is the relation? Answer: antagonist << Phenobarbital >> (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including [[ erythropoietin ]], heme oxygenase-1 and vascular endothelial growth factor-a. Question: what is the relation? Answer: indirect-upregulator In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, [[ DNMT-3a ]], and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Question: what is the relation? Answer: downregulator Acetylcholinesterase (<< AChE >>) inhibited by the [[ organophosphate ]] soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex. Question: what is the relation? Answer: inhibitor Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats. Question: what is the relation? Answer: upregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Question: what is the relation? Answer: agonist-activator Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, [[ tert-butylhydroquinone ]], cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments. Question: what is the relation? Answer: activator Phosphodiesterase type 5 (<< PDE5 >>) mediates the degradation of [[ cGMP ]] in a variety of tissues including brain. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 166,"Regarding the sentence ""However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]]."", what is the relation? activator Regarding the sentence ""However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of [[ metallothionein-II ]] production, and an increase in p53 activation and the pro-apoptotic protein Bax."", what is the relation? downregulator Regarding the sentence ""Overall, higher alcohol production was reduced by << ammonium >> supplementation, and this can be correlated with a general downregulation of genes encoding [[ decarboxylases ]] and dehydrogenases of the Ehrlich pathway."", what is the relation? indirect-downregulator Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist salbutamol 8 mg ([[ SAL ]]), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors."", what is the relation? agonist Regarding the sentence ""We have previously reported that TZDs reduce << estrogen >> synthesis by inhibiting [[ aromatase ]] activity in human granulosa cells (HGC)."", what is the relation? product-of Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""<< Doxorubicin >> is mainly excreted into the bile via P-glycoprotein ([[ P-gp ]]) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily."", what is the relation? substrate Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Terfenadine and astemizole are chemically unrelated to << histamine H1-receptor >> antagonists such as diphenhydramine and [[ chlorpheniramine ]]."", what is the relation? antagonist Regarding the sentence ""The beneficial role of << 17beta-estradiol >> on blood pressure, cardiac hypertrophy, vascular [[ osteopontin ]] expression, perivascular fibrosis, and impaired NO-dependent relaxation of isolated aortic rings was completely abrogated by coadministration of medroxyprogesterone acetate."", what is the relation? indirect-upregulator Regarding the sentence ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport."", what is the relation? upregulator Regarding the sentence ""Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=<< edrophonium >>=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of [[ acetylcholinesterase ]] also displaced [3H]-oxotremorine-M to the greatest extent."", what is the relation? inhibitor Regarding the sentence ""Hydrogen sulfide (H(2)S), a regulatory gaseous molecule that is endogenously synthesized by cystathionine gamma-lyase (<< CSE >>) and/or cystathionine beta-synthase (CBS) from L-cysteine ([[ L-Cys ]]) metabolism, is a putative vasodilator, and its role in nitric oxide (NO) production is unexplored."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 167,"Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, [[ glutamate synthase ]], and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings."". Can you identify the relation? downregulator Consider the text ""BACKGROUND & AIMS: Of the 2 genes (MAT1A, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes << S-adenosylmethionine >>, [[ MAT1A ]], is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues."". Can you identify the relation? product-of Consider the text ""Taken together, our study demonstrated that << SB365 >> inhibits the AKT/[[ mTOR ]] pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis."". Can you identify the relation? inhibitor Consider the text ""<< Amitriptyline >> is a [[ TrkA ]] and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity."". Can you identify the relation? agonist Consider the text ""In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of serotonin with transport-ready conformations of << SERT >> when concentrations of [[ serotonin ]] were low and rate limiting."". Can you identify the relation? substrate Consider the text ""Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."". Can you identify the relation? indirect-upregulator Consider the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."". Can you identify the relation? agonist-activator Consider the text ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.)."". Can you identify the relation? upregulator Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Activation of endogenous << somatostatin receptor subtype 2 >> (sst2) by [[ somatostatin-14 ]] or activation of transiently transfected rat D2 dopamine receptors (rD2(long)) by quinpirole had no effect."". Can you identify the relation? activator Consider the text ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of [[ R-spondins ]] (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD."". Can you identify the relation? indirect-downregulator Consider the text ""However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an N-methyl d-aspartate receptor ([[ NMDAR ]]) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting."". Can you identify the relation? antagonist Consider the text ""At nonconvulsant doses, the << sodium channel >> blockers acetylprocainamide, dibucaine, dyclonine, prilocaine, [[ proparacaine ]], quinidine, and tetracaine produced a small pressor response or no increase in BP."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 168,"Given that M-CSF signalling through << c-FMS >> plays an important role in osteoclast biology, we speculated that blocking such a pathway with [[ imatinib ]] may modulate osteoclast activity. what is the relation? inhibitor The influence of << (+/-)-tamsulosin >>, a selective [[ alpha 1A-adrenoceptor ]] antagonist, on the positive inotropic effect and the accumulation of inositol phosphates that are induced via alpha 1-adrenoceptors was studied in comparison with that of another alpha 1A-adrenoceptor ligand oxymetazoline in the rabbit ventricular myocardium. what is the relation? antagonist Our data identify << cAspAT >> as a new member of glyceroneogenesis, transcriptionally regulated by [[ TZD ]] via the control of RORalpha expression by PPARgamma in adipocytes. what is the relation? indirect-upregulator Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner. what is the relation? upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of There was no significant difference in TLR4, NF-κB, and << IL-27 >> mRNA and proteins between curcumin-treated and [[ sulfasalazine ]]-treated groups. what is the relation? indirect-downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor We have previously reported that TZDs reduce << estrogen >> synthesis by inhibiting [[ aromatase ]] activity in human granulosa cells (HGC). what is the relation? product-of In the locus coeruleus, brexpiprazole reversed the inhibitory effect of the preferential << 5-HT2A >> receptor agonist DOI ([[ 2,5-dimethoxy-4-iodoamphetamine ]]) on norepinephrine neuronal firing (ED50 = 110 mug/kg), demonstrating 5-HT2A antagonistic action. what is the relation? agonist Moreover, recent in vitro studies suggest that << memantine >> abrogates beta-amyloid ([[ Abeta ]]) toxicity and possibly inhibits Abeta production. what is the relation? downregulator We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (<< PhIP >>; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5. what is the relation? substrate << Epi >> increased the activity of the human WNT6 promoter through Cav1-dependent binding of β-catenin to the proximal [[ WNT6 promoter ]]. what is the relation? activator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. what is the relation? agonist-activator << Mammalian glutamate dehydrogenase >> (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of [[ l-glutamate ]] to 2-oxoglutarate using NAD(P)(+) as coenzyme. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 169,"In reference to ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, << 4-methoxy-2-naphthylamide >> of L-glutamic acid for [[ aminopeptidase A ]] and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B."", what is the relation? substrate In reference to ""<< EP(1) >> and EP(3) receptor antagonists ONO-8713 and [[ ONO-AE3-240 ]], but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."", what is the relation? antagonist In reference to ""In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of [[ ethylmorphine-N-demethylase ]] and aniline 4-hydroxylase activity and cytochrome P450, compared to the CCl4 only group."", what is the relation? activator In reference to ""Results showed that neonatal quinpirole treatment induced << D2 >> priming that was eliminated by [[ olanzapine ]] treatment."", what is the relation? indirect-downregulator In reference to ""Results showed that neonatal << quinpirole >> treatment induced [[ D2 ]] priming that was eliminated by olanzapine treatment."", what is the relation? indirect-upregulator In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Stereochemical studies established that << PAM >> inactivation by [[ 4-oxo-5-acetamido-6-(2-thienyl)-hex-2-enoic acid ]] is stereospecific with respect to the moiety at the P(2) position, which is consistent with previous results with substrates and reversible inhibitors."", what is the relation? inhibitor In reference to ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator In reference to ""Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index."", what is the relation? product-of In reference to ""The positive correlation between vitamin A and << immunoglobulin A >> concentrations might be the result of the [[ vitamin A ]] inductive effect during immunoglobulins A synthesis."", what is the relation? upregulator In reference to ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]]."", what is the relation? downregulator In reference to ""The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition."", what is the relation? agonist In reference to ""In addition to the effect on ROS, << puerarin >> ameliorated MPTP-reduced lysosome-associated membrane protein type 2A ([[ Lamp 2A ]]) expression."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 170,"Given the text ""In membranes from HEK293 cells transfected with alpha2-receptors, etomidate inhibited binding of the alpha2-antagonist, << [3H]RX821002 >>, with higher potency from alpha2B- and alpha2C-receptors than from [[ alpha2A-receptors ]] (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm)."", describe the relation. antagonist Given the text ""The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure."", describe the relation. agonist Given the text ""In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives (AA-861, [[ tBuBHQ ]], tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines."", describe the relation. activator Given the text ""Similarly, << felodipine >> and the p-chloro analogue inhibited [[ myosin light chain kinase ]] activity whether the isolated 20 kD light chain (IC50 = 12.6 microM) or intact myosin (IC50 = 11.0 microM) was used as substrate."", describe the relation. inhibitor Given the text ""To determine whether << 3,4-methylenedioxymethamphetamine >> (MDMA)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured."", describe the relation. downregulator Given the text ""At PND35, the medial prefrontal cortex (mPFC) of rats given << MPH >> showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less [[ norepinephrine transporter ]] (NET)-ir density."", describe the relation. indirect-downregulator Given the text ""Meanwhile, autophagy was detected as early as 12 h after an exposure to low-dose << dioscin >>, as indicated by an up-regulated expression of [[ LC3-II ]] and beclin-1 proteins."", describe the relation. indirect-upregulator Given the text ""<< LDH >> is responsible for pyruvate conversion to [[ lactate ]] through glycolysis."", describe the relation. product-of Given the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]."", describe the relation. upregulator Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and [[ catechol-O-methyltransferase ]] (COMT)."", describe the relation. substrate Given the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", describe the relation. agonist-activator Given the text ""However, several promising nonpeptide, << vasopressin receptor >> antagonists have been described; these agents are VPA-985 (lixivaptan), YM-087 (conivaptan), OPC-41061 (tolvaptan), and [[ SR-121463 ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 171,"Question: What is the relation in the sentence ""The latter reaction, catalyzed by << aspartoacylase >> (ASPA), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter.""? product-of Question: What is the relation in the sentence ""We show that both << darapladib >> and a novel class of structurally distinct carbamate inhibitors inactivate [[ Lp-PLA(2) ]] in mouse tissues and human cell lines with high selectivity.""? inhibitor Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]].""? upregulator Question: What is the relation in the sentence ""These results confirm the selective << mGlu2 >> agonist and mGlu3 antagonist actions of [[ LY541850 ]].""? agonist Question: What is the relation in the sentence ""Transport by << OATP1B1 >> and OATP1B3 enhances the cytotoxicity of epigallocatechin 3-O-gallate and several [[ quercetin ]] derivatives.""? substrate Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]).""? substrate_product-of Question: What is the relation in the sentence ""Galanin attenuates cyclic AMP regulatory element-binding protein (<< CREB >>) phosphorylation induced by chronic [[ morphine ]] and naloxone challenge in Cath.a cells and primary striatal cultures.""? activator Question: What is the relation in the sentence ""<< DNA methyltransferase 3a >> expression was increased in all [[ BPA ]] males and BPA 0.5 females and reduced in BPA 200 females.""? indirect-upregulator Question: What is the relation in the sentence ""Selective antagonism of GluR5 << kainate-receptor >>-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons.""? antagonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""<< Licofelone >> reduced intima/media ratio in injured arteries, the macrophages infiltration in the neointimal area, monocyte chemoattractant protein-1 ([[ MCP-1 ]]) gene expression, and the activation of nuclear factor-kappaB in rabbit atheroma.""? indirect-downregulator Question: What is the relation in the sentence ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]].""? downregulator Question: What is the relation in the sentence ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities.""? agonist-activator Question: What is the relation in the sentence ""One group of experimental animals was treated with << 5-lipoxygenase >> (5-LO) inhibitor, [[ diethylcarbamazine ]] (DEC, Sigma, St. Louis, Missouri) (50 mg/kg, i.v.), immediately before blast.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 172,"Given the text ""A dose of 25 microg kg(-1) day(-1) of << formoterol >> elicited greater EDL and soleus hypertrophy than salmeterol, but resulted in similar [[ beta-adrenoceptor ]] downregulation."", describe the relation. downregulator Given the text ""In all patients << loperamide >> induced a significant fall in plasma [[ ACTH ]] levels."", describe the relation. indirect-downregulator Given the text ""CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", describe the relation. upregulator Given the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", describe the relation. agonist-activator Given the text ""RESULTS: << Indomethacin >>, in vitro and in vivo. induces an increase in erythorcyte [[ CA I ]] and CA II activity."", describe the relation. activator Given the text ""Quantitative real-time polymerase chain reaction analysis showed that following the exposure of cells to << SiO(2) >> NPs, the messenger RNA level of apoptotic genes ([[ caspase-3 ]] and caspase-9) were upregulated in a dose-dependent manner."", describe the relation. indirect-upregulator Given the text ""We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase ([[ CHS ]]), and an antioxidant enzyme such as ascorbate peroxidase (APX)."", describe the relation. product-of Given the text ""The inhibition of << aminopeptidase >> activity in the presence of bestatin and [[ puromycin ]] inhibitors was also investigated."", describe the relation. inhibitor Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Although generally highly specific for << angiotensin II type 1 receptors >>, some ARBs, particularly [[ telmisartan ]], are partial agonists at peroxisome proliferator-activated receptor-γ."", describe the relation. antagonist Given the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""We found that reduction of the carcinogenic hydroxylamines of the << aromatic amine >> 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]."", describe the relation. substrate Given the text ""Pharmacology of << ramelteon >>, a selective [[ MT1 ]]/MT2 receptor agonist: a novel therapeutic drug for sleep disorders."", describe the relation. agonist Given the text ""We demonstrate that only treatment of HaCaT with << GLA >> and EPA or a PPARgamma ligand (roziglitazone), induced [[ COX-2 ]] expression (protein and mRNA)."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 173,"Given the text ""The memory-improving effect of minaprine on cycloheximide-induced amnesia was potentiated by a selective << 5-HT2 >> antagonist, [[ ritanserin ]]."", describe the relation. antagonist Given the text ""Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the << TCDD >>-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", describe the relation. indirect-upregulator Given the text ""Both << BB-94 >> and captopril also prevented substrate degradation by [[ gelatinase A and B ]] released in conditioned medium by cultured cells."", describe the relation. indirect-downregulator Given the text ""<< Indomethacin >> treatment led to an increase in lipid peroxidation, glutathione peroxidase and [[ glucose-6-phosphate dehydrogenase ]] activities and to a decrease in catalase activity and glutathione levels in gastric mucosa."", describe the relation. activator Given the text ""<< TAS-102 >> is a novel drug containing trifluorothymidine, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS."", describe the relation. substrate Given the text ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]]."", describe the relation. downregulator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""Thymidine kinase-1 (<< TK-1) >> and thymidylate synthase (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively."", describe the relation. product-of Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""It has been reported that oligomeric << procyanidins >> of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and [[ insulin ]]-potentiating activities."", describe the relation. upregulator Given the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", describe the relation. agonist-activator Given the text ""<< Ramelteon >> (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin [[ MT(1) ]]/MT(2) receptor agonist."", describe the relation. agonist Given the text ""Inhibition of gelatinase A (<< MMP-2 >>) by [[ batimastat ]] and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma."", describe the relation. inhibitor Given the text ""<< Histamine H(1) >> blockade is one of the more prominent actions of the multi-receptor acting antipsychotic [[ clozapine ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 174,"The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). Question: what is the relation? Answer: downregulator Uptake of the radiolabeled model substrates << estradiol 17β-glucuronide >>, estrone 3-sulfate, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either [[ OATP1B1 ]] or OATP1B3. Question: what is the relation? Answer: substrate Our results have shown that << MMP-9 >> messenger ribonucleic acid (mRNA) expression was inhibited by [[ doxycycline ]] starting at 10 mg/kg/day (P<0.02). Question: what is the relation? Answer: indirect-downregulator << Cobalt chloride >>, a typical HIF activator, induced the gene expression of CAR-target genes, including cyp2b9 and [[ cyp2b10 ]], an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver. Question: what is the relation? Answer: indirect-upregulator However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an N-methyl d-aspartate receptor ([[ NMDAR ]]) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting. Question: what is the relation? Answer: antagonist Nitric oxide products of << VP-16 >> displayed significantly diminished [[ topoisomerase II ]]-dependent cleavage of DNA and cytotoxicity to human HL-60 leukemia cells. Question: what is the relation? Answer: inhibitor Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity. Question: what is the relation? Answer: upregulator Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (ramelteon, << TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice. Question: what is the relation? Answer: agonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Question: what is the relation? Answer: substrate_product-of The latter reaction, catalyzed by aspartoacylase (<< ASPA >>), produces acetyl groups plus [[ aspartate ]] and has been proposed to occur in both soluble and membranous subfractions of white matter. Question: what is the relation? Answer: product-of << CCl(4) >> administration triggered inflammatory response in mice livers by activating [[ nuclear factor-kappaB ]] (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). Question: what is the relation? Answer: activator The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator This agent acts synergistically with many penicillins, such as ampicillin, carbenicillin, and the like, and with << cephalosporins >>, cefazolin, cefamandole, or cefoxitin to inhibit gram-negative bacilli, probably on the basis of binding to different proteins needed for the production of the [[ peptidoglycan ]] of the bacterial cell wall. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 175,"In the local presence into the LC of the << α2-adrenoceptor >> antagonist [[ RS79948 ]] (1 μM), systemic citalopram increased NA in the LC (Emax = 157 ± 25 %) and PFC (Emax = 175 ± 24 %). Please explain the relation. antagonist These data suggest that inhibition of << JAK2 >>/STAT3 signaling is a novel mechanism of action for [[ PTE ]] during therapeutic intervention in osteosarcoma cancers. Please explain the relation. inhibitor In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to << AMP >> by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase. Please explain the relation. product-of Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Please explain the relation. agonist-activator << ABCA1 >> mediates the efflux of unesterified [[ cholesterol ]] and phospholipids from cells to lipid-poor apolipoprotein A-I (apoA-I). Please explain the relation. substrate Lastly, we found that << RhoA >> activation by [[ cucurbitacin I ]] is mediated by reactive oxygen species (ROS). Please explain the relation. activator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of << PTE >> also down-regulated the expression of [[ STAT3 ]] target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. Please explain the relation. indirect-downregulator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53. Please explain the relation. upregulator << Ozone >> plus PM(2.5) exposure, however, induced CRP, [[ IL-6 ]], CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way. Please explain the relation. indirect-upregulator However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of [[ metallothionein-II ]] production, and an increase in p53 activation and the pro-apoptotic protein Bax. Please explain the relation. downregulator Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist acetylcholine ([[ ACh ]]) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump. Please explain the relation. agonist << Ibrutinib >> (Imbruvica(R)) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton's tyrosine kinase ([[ BTK ]]) that inhibits B-cell antigen receptor signalling downstream of BTK. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 176,"Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists. Question: what is the relation? Answer: antagonist << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein ([[ pRb ]]), and the upregulation of p21(WAF1/CIP1) and p53. Question: what is the relation? Answer: downregulator Pre-clinical pharmacology of << zolmitriptan >> (Zomig; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine. Question: what is the relation? Answer: agonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Question: what is the relation? Answer: substrate_product-of Similarly, pretreatment with << sulindac sulfide >> blocks the ability of EGF to induce ERK1/2 and [[ Bad ]] phosphorylation, but also down-regulates total Bad but not ERK1/2 protein levels. Question: what is the relation? Answer: inhibitor Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. Question: what is the relation? Answer: upregulator << Methionine synthase reductase >> (MTRR) is an enzyme involved in the conversion of Hcy to [[ methionine ]]. Question: what is the relation? Answer: product-of Choline dehydrogenase (<< CHDH >>) and betaine-homocysteine methyltransferase (BHMT) are 2 enzymes involved in [[ choline ]] oxidation. Question: what is the relation? Answer: substrate Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor Furthermore, << substance P >> (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (NK-1R), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells. Question: what is the relation? Answer: indirect-upregulator RESULTS: << Indomethacin >>, in vitro and in vivo. induces an increase in erythorcyte [[ CA I ]] and CA II activity. Question: what is the relation? Answer: activator In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: agonist-activator Co-treatment of astrocytes with << antofine >> and the intracellular Ca(2+) chelator BAPTA-AM prevented downregulation of [[ Cx43 ]] and inhibition of GJIC. Question: what is the relation? Answer: indirect-downregulator Down-regulation of prostate-specific antigen (<< PSA >>) expression, an AR-target gene, by estramustine and [[ bicalutamide ]] was accompanied by the blockade of the mutated androgen receptor. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 177,"Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."". Can you identify the relation? substrate_product-of Consider the text ""Histamine content, HDC activity and << HDC >> mRNA expression in nasal mucosa were also significantly increased after [[ TDI ]] provocation."". Can you identify the relation? indirect-upregulator Consider the text ""<< Sulindac sulfide >> inhibited [[ 14-3-3epsilon proteins ]] in HT-29 and DLD-1 cells in a time- and concentration-dependent manner."". Can you identify the relation? indirect-downregulator Consider the text ""Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]."". Can you identify the relation? upregulator Consider the text ""<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two PtdSer synthases, [[ PSS1 ]] and PSS2."". Can you identify the relation? product-of Consider the text ""<< Phillyrin >> attenuates high glucose-induced lipid accumulation in human HepG2 hepatocytes through the activation of LKB1/[[ AMP-activated protein kinase ]]-dependent signalling."". Can you identify the relation? activator Consider the text ""EP(1) and << EP(3) receptor >> antagonists ONO-8713 and [[ ONO-AE3-240 ]], but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."". Can you identify the relation? antagonist Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""Two beta(2)-agonists, << formoterol >> and salmeterol, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity."". Can you identify the relation? agonist Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, [[ cyclin dependent kinase 2 ]] (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."". Can you identify the relation? downregulator Consider the text ""Then the cells were treated with various concentrations of apoE3, lactoferrin and bovine serum albumin with or without 100 microg/ml of GMC, and the << SGLT1 >>-dependent [[ methyl alpha-D-glucopyranoside ]] (AMG) uptake and levels of SGLT1 expression were determined."". Can you identify the relation? substrate Consider the text ""Furthermore, << auranofin >> inhibited [[ NF-kappaB ]] activation induced by MyD88-dependent downstream signaling components of TLR4, MyD88, IKKbeta, and p65."". Can you identify the relation? inhibitor Consider the text ""The mechanism of << PAK1 >> inhibition and induction of membranous translocation of adhesion proteins by [[ 5-ASA ]] might be independent of its known anti-inflammatory action."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 178,"One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory cytokines, increased [[ adiponectin ]] expression and improved glucose tolerance parallel to insulin sensitivity in obese mice. what is the relation? indirect-upregulator The << calcium >> homeostasis proteins [[ sarcoendoplasmic reticulum ATPase 2a ]] (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation. what is the relation? substrate Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. what is the relation? upregulator Inhibition of p95ErbB2, p185ErbB2, and EGFR phosphorylation by << GW572016 >> resulted in the inhibition of downstream phospho-[[ Erk1/2 ]], phospho-AKT, and cyclin D steady-state protein levels. what is the relation? indirect-downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific << renin >>-angiotensin-aldosterone system (RAAS) blockade by renin-inhibitor [[ remikiren ]] could be predicted from pretreatment renal vascular tone. what is the relation? inhibitor The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator Phosphorylation of ER-stress marker << eIF2α >> was also increased but only at 30 min of [[ 2-deoxyglucose ]] exposure. what is the relation? activator These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from << xanthine oxidase >>-generated [[ superoxide ]] and NO. what is the relation? product-of The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the << 5-HT1A >> receptor antagonist [[ spiroxatrine ]] (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM). what is the relation? antagonist << D-Serine >> was previously identified in mammalian brain and was shown to be a co-agonist at the 'glycine' site of the [[ N-methyl-D-aspartate (NMDA)-type receptors ]]. what is the relation? agonist << PKC >> isoforms did show different sensitivity and selectivity for down-regulation by [[ I3A ]] and phorbol 12-myristate 13-acetate (PMA) in WEHI-231, HOP-92, and Colo-205 cells. what is the relation? downregulator The most potent compound 5 (<< HJC0123 >>) has demonstrated to inhibit STAT3 promoter activity, downregulate phosphorylation of [[ STAT3 ]], increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 179,"Consider the text ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."". Can you identify the relation? upregulator Consider the text ""Lastly, we found that << RhoA >> activation by [[ cucurbitacin I ]] is mediated by reactive oxygen species (ROS)."". Can you identify the relation? activator Consider the text ""In the long term, << orlistat >> has been shown to be more effective than placebo in reducing body weight and serum total and [[ low-density lipoprotein ]] cholesterol levels."". Can you identify the relation? indirect-downregulator Consider the text ""In the lateral geniculate nucleus, << brexpiprazole >> displayed [[ alpha1B-adrenoceptor ]] antagonistic action."". Can you identify the relation? antagonist Consider the text ""As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and << xanthine oxidase >> was identified as the likely source of [[ TES ]]-stimulated superoxide production."". Can you identify the relation? product-of Consider the text ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]]."". Can you identify the relation? downregulator Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective << 5-HT1F >> receptor agonist ([[ LY 344864 ]]) on c-fos protein expression in the trigeminal nucleus caudalis."". Can you identify the relation? agonist Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""<< Doxorubicin >> is mainly excreted into the bile via P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 ([[ Mrp2 ]]) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily."". Can you identify the relation? substrate Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Pregnane X Receptor Mediates Dyslipidemia Induced by the << HIV Protease >> Inhibitor [[ Amprenavir ]] in Mice."". Can you identify the relation? inhibitor Consider the text ""CONCLUSIONS A diet that partially replaces << carbohydrate >> with unsaturated fat may improve [[ insulin ]] sensitivity in a population at risk for cardiovascular disease."". Can you identify the relation? indirect-upregulator Consider the text ""The transcriptional activity of torafugu PPARalpha1 was enhanced 4.5- and 11.5-fold by Wy-14643 and << 5,8,11,14-eicosatetraynoic acid >> (ETYA) each at 10 microM, respectively, whereas that of [[ PPARalpha2 ]], 4.5- and 7.3-fold at the same concentration of the respective ligands, respectively."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 180,"Regarding the sentence ""<< Doxorubicin >> is mainly excreted into the bile via [[ P-glycoprotein ]] (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily."", what is the relation? substrate Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor Regarding the sentence ""<< Adenosine >> and N(6)-cyclopentyl-adenosine (CPA, [[ A1R ]] agonist) constricted MVs but not MAs."", what is the relation? agonist Regarding the sentence ""In another experiment, << cyanopindolol >>, an antagonist of the [[ serotonin terminal autoreceptor ]], also prolonged the clearance of 5-HT from the CA3 region."", what is the relation? antagonist Regarding the sentence ""Thymidine kinase-1 (TK-1) and << thymidylate synthase >> (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively."", what is the relation? product-of Regarding the sentence ""Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent [[ HO-1 ]] activity."", what is the relation? downregulator Regarding the sentence ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", what is the relation? agonist-activator Regarding the sentence ""Saturated << palmitic and stearic acids >> increased ceramides, up-regulated PTP1B, and had AKt and [[ PTP1B ]] phosphorylation at Ser 50 impaired."", what is the relation? activator Regarding the sentence ""Although Bak and Bcl-2-associated X protein (Bax), another member of the Bcl-2 family, are generally thought to be functionally redundant, only Bak is necessary and sufficient for << VK2 >>-induced [[ cytochrome c ]] (cyt c) release and cell death."", what is the relation? indirect-upregulator Regarding the sentence ""Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line."", what is the relation? upregulator Regarding the sentence ""Considerable attention has focused on the antitumor effect of << histone deacetylase >> inhibitor ([[ Trichostatin A ]], TSA) as well as the coding gene expression-induced apoptosis of cancer cells."", what is the relation? inhibitor Regarding the sentence ""Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and transforming growth factor-β1 (<< TGF-β1 >>), were reduced in rats treated with [[ sinapic acid ]]."", what is the relation? indirect-downregulator Regarding the sentence ""Furthermore, they suggest that << TRPML1 >> works in concert with ZnT4 to regulate [[ zinc ]] translocation between the cytoplasm and lysosomes."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 181,"Regarding ""Treatment with diclofenac resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated caspase-3 after 6 hr, indicating that << diclofenac >> may cause apoptosis of neuronal cells via activation of the [[ caspase ]] cascade."", can you determine the relation? activator Regarding ""Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats."", can you determine the relation? upregulator Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", can you determine the relation? agonist Regarding ""Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 [[ p28 ]] protein (p < 0.05)."", can you determine the relation? indirect-downregulator Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""<< LTD4 >> also induced expression of cysteinyl leukotriene receptor 1 (CysLT(1)R) and [[ NF-κB ]] p65 in the hippocampus and cortex."", can you determine the relation? indirect-upregulator Regarding ""<< SC-51089 >> (10(-5) M), a selective [[ EP1-receptor ]] antagonist, showed no effect on the PGE1- or PGE2-induced inhibition of the HVA ICa, thereby indicating that PGE1- and PGE2-induced inhibition of the HVA Ca2+ channels is possibly mediated by the EP3 receptor."", can you determine the relation? antagonist Regarding ""Expression of the dominant negative mutants rab5A-N133I or << rab7 >>-N125I blunted [[ U50,488H ]]-induced down-regulation."", can you determine the relation? downregulator Regarding ""One major route involves the tetrahydrofolate (THF)-dependent activities of the << glycine decarboxylase complex >> (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source."", can you determine the relation? substrate Regarding ""4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, Cl, << Br >>) derivatives are first-generation dual aromatase and [[ sulfatase ]] inhibitors (DASIs)."", can you determine the relation? inhibitor Regarding ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", can you determine the relation? agonist-activator Regarding ""Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of spermidine and [[ spermine ]] with a significant accumulation of putrescine and induction of ODC."", can you determine the relation? product-of Regarding ""Biological evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4 (DPP-4) inhibitors, among them, the << cyclopropyl-substituted phenylalanine >> derivative 11h displayed the most potent [[ DPP-4 ]] inhibitory activity with an IC50 value of 0.247 μM."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 182,"The selective << beta1AR >> antagonists [[ atenolol ]] and metoprolol blocked isoproterenol-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively. Please explain the relation. antagonist Transduction with constitutively active forms of GSK-3β could protect against the downregulation of p65 and upregulation of cleaved-<< PARP >> that are induced by [[ cinobufagin ]] treatment. Please explain the relation. indirect-upregulator In addition to this pronounced loss of function, << M1766L >> also showed a 10-fold increase in the persistent late [[ sodium ]] current. Please explain the relation. upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, [[ HSF1 ]], AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins. Please explain the relation. activator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator Phospholipase A2 inhibitors << p-bromophenacyl bromide >> and arachidonyl trifluoromethyl ketone suppressed interleukin-2 ([[ IL-2 ]]) expression in murine primary splenocytes. Please explain the relation. indirect-downregulator This surprising correlation between the lack of OTC expression and sensitivity of ASS-positive HCC cells shows that OTC-deficient HCCs are sensitive to << rhArg >>-mediated [[ arginine ]] depletion. Please explain the relation. substrate << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein ([[ pRb ]]), and the upregulation of p21(WAF1/CIP1) and p53. Please explain the relation. downregulator << Indomethacin >> and SC-236, a selective cyclooxygenase-2 ([[ COX-2 ]]) inhibitor, exerted a similar effect as sulindac. Please explain the relation. inhibitor << D-Serine >> was previously identified in mammalian brain and was shown to be a co-agonist at the 'glycine' site of the [[ N-methyl-D-aspartate (NMDA)-type receptors ]]. Please explain the relation. agonist Ferredoxin 1 (<< FDX1 >>; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues. Please explain the relation. product-of The Bcl2/<< Bax >> ratio increased and Mfn2 expression decreased in MIN6 cells after [[ glucose ]] stimulation. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 183,"The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. what is the relation? agonist-activator Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists. what is the relation? antagonist These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves. what is the relation? agonist Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and [[ JNK1/2 ]] activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR. what is the relation? upregulator The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase ([[ SOD ]]) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. what is the relation? downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. what is the relation? substrate_product-of << Ferredoxin 1 >> (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues. what is the relation? product-of Conversely, opioid antagonists such as naloxone and << naltrexone >> (which bind to non-selectively [[ opioid receptors ]]) have been shown to decrease alcohol consumption under various experimental conditions. what is the relation? activator Furthermore, << N >>-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and [[ mTOR ]] via suppression of Ras prenylation and enhanced Bim expression. what is the relation? indirect-downregulator Mitiglinide (<< KAD-1229 >>), a new anti-diabetic drug, is thought to stimulate [[ insulin ]] secretion by closing the ATP-sensitive K+ (K(ATP)) channels in pancreatic beta-cells. what is the relation? indirect-upregulator Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and << clofarabine >> is linked to the inhibition of Akt and [[ Sp1 ]] activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma. what is the relation? inhibitor Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor << Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as [[ ketone ]] bodies. what is the relation? substrate The identity of the lung << beta-ADHs >> was further demonstrated by their characteristic pH-activity profiles for ethanol oxidation, Km values for NAD and ethanol, and inhibition by 4-methylpyrazole or [[ 1,10-phenanthroline ]]. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 184,"In reference to ""In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives ([[ AA-861 ]], tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines."", what is the relation? activator In reference to ""Saturated << palmitic and stearic acids >> increased ceramides, up-regulated [[ PTP1B ]], and had AKt and PTP1B phosphorylation at Ser 50 impaired."", what is the relation? upregulator In reference to ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""<< Ferredoxin 1 >> (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues."", what is the relation? product-of In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", what is the relation? substrate_product-of In reference to ""Both 5'-AMN and << 5'-MABN >> had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and [[ μ-receptor ]] antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum."", what is the relation? antagonist In reference to ""Recombinant << PDE10A >> transfected and expressed in COS-7 cells hydrolyzed [[ cAMP ]] and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with cAMP."", what is the relation? substrate In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of << WIN 55,212 >> antagonized by the [[ CB2 ]] antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]."", what is the relation? agonist In reference to ""In the << IB-MECA >> group, [[ α-amylase ]] activity was decreased with statistically high significance compared to group I."", what is the relation? indirect-downregulator In reference to ""<< Orlistat >> treatment also results in modest improvements in total cholesterol, [[ low-density lipoprotein ]], blood pressure, and fasting glucose and insulin concentrations."", what is the relation? indirect-upregulator In reference to ""Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit << HVA Ca2+ channels >> was [[ sulprostone ]]>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2."", what is the relation? inhibitor In reference to ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, [[ MBD-2 ]] and MBD-3), in MEF cells by the proteasomal pathway."", what is the relation? downregulator In reference to ""Sorafenib and sunitinib are synthetic, orally active agents shown to directly inhibit vascular endothelial growth factor receptors -2 and -3 (VEGFR-2, VEGFR-3) and platelet-derived growth factor receptor beta (PDGFR-beta), while << temsirolimus >> is an [[ mTOR ]] inhibitor."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 185,"In addition, by comparing the combined administration of (+/-)pindolol with either WAY100635, GR127935 or isamoltane, we have determined that << (+/-)pindolol >> produces much of its acute potentiation of fluoxetine-induced increases in extracellular 5-HT via its action at the 5-HT(1B/D) receptor in addition to any activity it has at the presynaptic [[ 5-HT(1A) ]] receptor. what is the relation? antagonist In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. what is the relation? agonist-activator << Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/[[ c-Src ]]/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway. what is the relation? indirect-downregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of These results suggest that << HSD11B1 >>-derived [[ cortisol ]] mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep. what is the relation? product-of The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). what is the relation? agonist The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and [[ BT-03 ]] possessing asymmetric structure. what is the relation? activator The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, [[ glutamine synthetase ]], glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings. what is the relation? downregulator Culture of HepG2 cells with << griseofulvin >> has now been shown to induce both the formation of intracellular aggregates containing [[ K18 ]] as well as an increase in the abundance of K18 mRNA. what is the relation? indirect-upregulator Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats. what is the relation? upregulator Taken together, these data demonstrate that baicalin inhibits the metabolism of << DXM >> in a concentration-dependent manner in rats, possibly through inhibiting hepatic [[ CYP2D ]] and CYP3A activities. what is the relation? substrate No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary [[ efflux transporters ]] BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells. what is the relation? inhibitor Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor In cell culture experiments, it was found that triclosan inhibited << IL-1 beta >> induced [[ prostaglandin E2 ]] production by human gingival fibroblasts in a concentration dependent manner, and at relatively low concentrations. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 186,"Given the text ""<< Cyclooxygenase(COX)-2 >>-derived [[ prostanoids ]] can influence several processes that are linked to carcinogenesis."", describe the relation. product-of Given the text ""Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of [[ β-catenin ]]-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc."", describe the relation. indirect-downregulator Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Type I deiodinase, liver fatty-acid binding protein and << cytochrome P450 (CYP) 3A37 >> mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1."", describe the relation. indirect-upregulator Given the text ""Zolmitriptan (<< Zomig >>; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura."", describe the relation. agonist Given the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""<< Triacsin C >>, a competitive inhibitor of both ACS1 and [[ ACS4 ]], inhibited ACS activity similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting that a hitherto unidentified triacsin-sensitive ACS is present in mitochondria."", describe the relation. inhibitor Given the text ""<< Conivaptan >> is a nonpeptide dual [[ V1a/V2 AVP receptor ]] antagonist."", describe the relation. antagonist Given the text ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using << dexamethasone 21-phosphate >> (DEX-P) and midazolam (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively."", describe the relation. substrate Given the text ""<< NCFP >> binds to the CPPHA site on mGlu5 and potentiates [[ mGlu5 ]]-mediated responses in both recombinant and native systems."", describe the relation. activator Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (<< M/TPO-Ag >>) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis."", describe the relation. upregulator Given the text ""Second, << probucol >>, an antiatherogenic compound reported to be an inactivator of [[ ABCA1 ]] reduced hepatic alpha-tocopherol secretion."", describe the relation. downregulator Given the text ""In contrast, TSH-induced differentiation of progenitor cells, in particular the expression of the << sodium iodide symporter >>, was significantly inhibited by [[ 17beta-oestradiol ]].In conclusion, oestrogen stimulated growth and simultaneously inhibited differentiation of thyroid nodules derived stem/progenitor cells."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 187,"Given the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of [[ p21 ]](WAF1/CIP1) and p53."", describe the relation. upregulator Given the text ""The studies with dThyd rescue from << cyclin E >>-cdk2 protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance."", describe the relation. indirect-upregulator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", describe the relation. substrate_product-of Given the text ""It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a [[ BRCA2 ]] mutation."", describe the relation. downregulator Given the text ""In contrast, the selective << beta2AR >> antagonists ICI-118,551 and [[ butoxamine ]] inhibited isoproterenol-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively)."", describe the relation. antagonist Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""FCEO significantly inhibited nitric oxide (<< NO >>) and prostaglandin E2 (PGE2) by suppressing the protein expression of [[ inducible nitric oxide synthase ]] (iNOS) and cyclooxygenase (COX)-2, respectively."", describe the relation. indirect-downregulator Given the text ""Assays examining the ability of << TFP >> to block [[ S100A4 ]]-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of S100A4 function occurs only at TFP concentrations that promote S100A4 oligomerization."", describe the relation. inhibitor Given the text ""In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of << cAMP >> to AMP by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase."", describe the relation. substrate Given the text ""The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", describe the relation. agonist Given the text ""<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha ([[ TNF-α ]]) and cyclooxygenase-2 (COX-2)."", describe the relation. activator Given the text ""Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS)."", describe the relation. product-of Given the text ""The << ATP >> required for potentiation of skeletal muscle contraction is released via [[ pannexin ]] hemichannels."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 188,"Consider the text ""Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, << kuraridin >> ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT)."". Can you identify the relation? inhibitor Consider the text ""alpha(1)-Adrenoceptor antagonists were tested against the << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach."". Can you identify the relation? agonist Consider the text ""4-Hydroxynonenal (<< 4-HNE >>) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several glutathione S-transferase ([[ GST ]]) isoforms."". Can you identify the relation? substrate Consider the text ""Mutation of arginine 228 to << lysine >> enhances the [[ glucosyltransferase ]] activity of bovine beta-1,4-galactosyltransferase I."". Can you identify the relation? upregulator Consider the text ""Similar to gemfibrozil, << clofibrate >>, another fibrate drug, also inhibited the expression of [[ iNOS ]]."". Can you identify the relation? indirect-downregulator Consider the text ""Suppression of Src/<< ERK >> and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells."". Can you identify the relation? downregulator Consider the text ""In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of [[ HSP70 ]] and Bax proteins."". Can you identify the relation? indirect-upregulator Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, [[ cinnamic aldehyde ]], and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."". Can you identify the relation? activator Consider the text ""METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist ([[ SB-207266 ]]) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects."". Can you identify the relation? antagonist Consider the text ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (<< 5-FU >>) by [[ thymidine phosphorylase ]] (TP) inside target tissues."". Can you identify the relation? product-of Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""Our study revealed that high glucose/<< Fe >> concentrations in MIN6 cells induced an increase of the Bcl2/[[ Bax ]] ratio, an indicator of increased cell apoptosis."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 189,"Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves. Please explain the relation. agonist << Statins >> increase p21 through inhibition of histone deacetylase activity and release of promoter-associated [[ HDAC1/2 ]]. Please explain the relation. upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of These data demonstrated that 1) gemcitabine and << pemetrexed >> synergistically interact against NSCLC cells through the suppression of [[ Akt ]] phosphorylation and induction of apoptosis; 2) the gene expression profile of critical genes may predict for drug chemosensitivity; and 3) pemetrexed enhances dCK and hENT1 expression, thus suggesting the role of gene-expression modulation for rational development of chemotherapy combinations. Please explain the relation. inhibitor To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, << sodium hydrosulphide >> (NaHS), (10, 50 and 100 muM), that resulted in a significant increase in SP concentration and expression of PPT-A and [[ NK1-R ]] in acinar cells. Please explain the relation. indirect-upregulator Under isotonic conditions, << N-ethylmaleimide >> (NEM) produced [[ KCC ]] activation and transient cell shrinkage. Please explain the relation. activator The << M564G >> mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward [[ myristoyl-CoA ]] was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA. Please explain the relation. substrate Humans with << FSH beta >> gene mutations tend to have a more severe phenotype than those with FSHR gene mutations, although infertility and varying degrees of impaired sex [[ steroid ]] production occur in both types of mutations. Please explain the relation. product-of << EP(1) >> and EP(3) receptor antagonists [[ ONO-8713 ]] and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth. Please explain the relation. antagonist Neonatal << quinpirole >> treatment produced a significant decrease in BDNF and [[ ChAT ]] in the frontal cortex that was unaffected by olanzapine treatment. Please explain the relation. indirect-downregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, [[ cyclin A ]], cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Please explain the relation. downregulator The MCAO-induced decrease in << insulin receptor >> levels in the liver and skeletal muscle on day 1 was recovered to control levels by orexin-A, and this effect of orexin-A was reversed by the administration of [[ SB334867 ]] as well as by hypothalamic BDNF knockdown. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 190,"In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. what is the relation? agonist-activator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of Using a transient heterologous cell expression system, we find that the transport activities of the << short OATP2B1 >> variant towards substrates [[ estrone sulfate ]] and rosuvastatin are similar to the well-characterized full length variant. what is the relation? substrate Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor These findings suggest that << S1P >> activates the PI3K/[[ Akt ]] signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively. what is the relation? activator Compared pharmacological characteristics in humans of racemic cetirizine and << levocetirizine >>, two [[ histamine H1-receptor ]] antagonists. what is the relation? antagonist The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific). what is the relation? agonist These findings suggest that << S1P >> activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including [[ alkaline phosphatase ]], probably relating to the inhibition of osteoclast formation and the mineralization, respectively. what is the relation? indirect-upregulator In conclusion, we find that << sinapic acid >> exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress [[ TGF-β1 ]] and its ability to attenuate activation of hepatic stellate cells. what is the relation? indirect-downregulator CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme. what is the relation? upregulator In addition, << ethanol >> induced degradation of [[ DNA methyltransferases ]] (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. what is the relation? downregulator PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2]. what is the relation? product-of Everolimus (RAD001, << Afinitor((R)) Novartis >>) is the first oral inhibitor of mTOR ([[ mammalian target of rapamycin ]]) to reach the oncology clinic. what is the relation? inhibitor Combination chemotherapy with a << substance P receptor >> antagonist ([[ aprepitant ]]) and melarsoprol in a mouse model of human African trypanosomiasis. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 191,"Question: What is the relation in the sentence ""Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the << TCDD >>-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.""? indirect-upregulator Question: What is the relation in the sentence ""BACKGROUND & AIMS: Of the 2 genes (MAT1A, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes << S-adenosylmethionine >>, [[ MAT1A ]], is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues.""? product-of Question: What is the relation in the sentence ""<< LY541850 >> was claimed from human mGlu receptors expressed in non-neuronal cells to be a selective orthosteric mGlu2 agonist and [[ mGlu3 ]] antagonist.""? antagonist Question: What is the relation in the sentence ""AIM: To assess the efficacy and safety of a 24-week treatment with << sitagliptin >>, a highly selective once-daily oral [[ dipeptidyl peptidase-4 ]] (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and >-induced MAPK, JNK and [[ p38 ]](MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.""? activator Question: What is the relation in the sentence ""Additionally, the expression of hepatic fibrosis-related factors such as << α-smooth muscle actin >> and transforming growth factor-β1 (TGF-β1), were reduced in rats treated with [[ sinapic acid ]].""? indirect-downregulator Question: What is the relation in the sentence ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific).""? agonist Question: What is the relation in the sentence ""<< Mammalian ALDH1B1 >>, another mitochondrial enzyme sharing 72% identity with ALDH2, is also capable of metabolizing [[ acetaldehyde ]] but has a tissue distribution and pattern of activity distinct from that of ALDH2.""? substrate Question: What is the relation in the sentence ""<< Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity.""? upregulator Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities.""? agonist-activator Question: What is the relation in the sentence ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced << NADPH oxidase >> activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by [[ resveratrol ]].""? downregulator Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""Troglitazone, bosentan and glibenclamide inhibit the << bile salt export pump >> (Bsep) which transports [[ taurocholate ]] into bile.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 192,"Given the text ""Terbutaline (Bricanyl) and its prodrug << Bambuterol >> (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients."", describe the relation. agonist Given the text ""Pharmacologically, << troglitazone >> is a novel inhibitor of [[ ENT1 ]]."", describe the relation. inhibitor Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", describe the relation. agonist-activator Given the text ""These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans."", describe the relation. upregulator Given the text ""From these data, it is inferred that both the SERT and << NET >> contribute to the active clearance of exogenously applied [[ 5-HT ]] in the dentate gyrus."", describe the relation. substrate Given the text ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."", describe the relation. downregulator Given the text ""<< CDCA >> induced dose-dependent expression of Cdx2 and [[ MUC2 ]] at both the mRNA and protein levels."", describe the relation. indirect-upregulator Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""<< Aldose reductase >> (AR) catalyzes the reduction of toxic lipid aldehydes to their [[ alcohol ]] products and mediates inflammatory signals triggered by lipopolysaccharide (LPS)."", describe the relation. product-of Given the text ""Western blotting demonstrated that << DMBT >> effectively suppressed the expression of VEGF, [[ p-VEGFR-2 ]], p-EGFR, and p-Akt."", describe the relation. indirect-downregulator Given the text ""<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and [[ cyclooxygenase-2 ]] (COX-2)."", describe the relation. activator Given the text ""Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as GluN1/[[ GluN2B ]] N-Methyl-D-aspartate Receptor Antagonists."", describe the relation. antagonist Given the text ""In complementary RNA (cRNA)-injected Xenopus laevis oocytes, << rifamycin SV >> (10 micromol/L) cis-inhibited human organic anion transporting polypeptide C (SLC21A6) (OATP-C), human organic anion transporting polypeptide 8 (SLC21A8) (OATP8), human organic anion transporting polypeptide B (SLC21A9) (OATP-B), and [[ human organic anion transporting polypeptide A ]] (SLC21A3) (OATP-A) mediated BSP uptake by 69%, 79%, 89%, and 57%, respectively, as compared with uptake into control oocytes."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 193,"Question: What is the relation in the sentence ""<< Rofecoxib >> only diminished [[ COX-2 ]] protein expression and MCP-1 gene expression in vascular atheroma.""? indirect-downregulator Question: What is the relation in the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and << midazolam >> (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.""? activator Question: What is the relation in the sentence ""These results suggest that << CYP2B6 >> genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of [[ bupropion ]].""? substrate Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]].""? agonist-activator Question: What is the relation in the sentence ""Moreover, << S1611 >> and S3226, both specific inhibitors of [[ NHE3 ]] only, or perfusion with Na+-free solutions, dose dependently increased DBS, as measured by pH-stat and CO2-sensitive electrode, without affecting intracellular pH.""? inhibitor Question: What is the relation in the sentence ""Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of << fisetin >> on [[ mTOR ]].""? downregulator Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the << dopamine D1 receptor >> antagonist SCH 39166 ([[ (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine ]]) and the dopamine D2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg).""? antagonist Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""These results suggest that ACS1 and << ACS4 >> may be linked to [[ triacylglycerol ]] synthesis.""? product-of Question: What is the relation in the sentence ""In PFC, << DEX >> caused activation of AKT, augmentation of pro-survival Bcl-2 protein and enhanced Bcl-2/[[ Bax ]] protein ratio, as well Bcl-2 translocation to mitochondria.""? indirect-upregulator Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53.""? upregulator Question: What is the relation in the sentence ""The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific).""? agonist Question: What is the relation in the sentence ""Glinides, << sulfonylureas >>, and other acidified sulfonamides may be promising leads in the development of new [[ PPARgamma ]] agonists.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 194,"Regarding ""CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", can you determine the relation? upregulator Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Aldose reductase (<< AR >>) catalyzes the reduction of toxic lipid aldehydes to their [[ alcohol ]] products and mediates inflammatory signals triggered by lipopolysaccharide (LPS)."", can you determine the relation? product-of Regarding ""To this end, 158N murine oligodendrocytes were treated with 7KC or << 7βOHC >> inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and [[ caspase-3 ]] activation."", can you determine the relation? activator Regarding ""Second, << ICRF-187 >>, a [[ Top2 ]] catalytic inhibitor known to deplete Top2β, specifically sensitized MEFs to CPT."", can you determine the relation? inhibitor Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", can you determine the relation? agonist-activator Regarding ""Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats."", can you determine the relation? downregulator Regarding ""<< Zolmitriptan >> (Zomig; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura."", can you determine the relation? agonist Regarding ""Our results showed that low dose << BPA >> and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of [[ Oct4 ]] and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein."", can you determine the relation? indirect-upregulator Regarding ""Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase ([[ ERK ]]) and mTOR via suppression of Ras prenylation and enhanced Bim expression."", can you determine the relation? indirect-downregulator Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< Carboxylesterases >> hydrolyze [[ esters ]], amides, and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively."", can you determine the relation? substrate Regarding ""The putative << alpha 1L-adrenoceptor >> antagonist [[ JTH-601 ]], but not the alpha 1B-adrenoceptor antagonist chloroethylclonidine (10 microM) antagonized noradrenaline-induced contractions of SMA."", can you determine the relation? antagonist Regarding ""In HaCaT cells, buthanol and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (<< CLS >>) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 ([[ COX-2 ]]), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α)."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 195,"Regarding ""Polyclonal antisera to either b5R or << cyt b5 >> significantly inhibited N-hydroxy-4-aminobiphenyl ([[ NHOH-4-ABP ]]) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP)."", can you determine the relation? substrate Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [[[ PI(4,5)P2 ]]]."", can you determine the relation? product-of Regarding ""The antagonistic property of << rilmenidine >> at [[ human alpha(2A)-adrenoceptors ]] indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved."", can you determine the relation? antagonist Regarding ""Pharmacokinetic Interactions between << Monoamine Oxidase A >> Inhibitor [[ Harmaline ]] and 5-Methoxy-N,N-Dimethyltryptamine, and the Impact of CYP2D6 Status."", can you determine the relation? inhibitor Regarding ""The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, [[ glutamine synthetase ]], glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings."", can you determine the relation? downregulator Regarding ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", can you determine the relation? agonist Regarding ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< Orlistat >> treatment also results in modest improvements in total cholesterol, [[ low-density lipoprotein ]], blood pressure, and fasting glucose and insulin concentrations."", can you determine the relation? indirect-upregulator Regarding ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, [[ TMB-4 ]] and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure."", can you determine the relation? activator Regarding ""Moreover, LTD4-induced increases in CysLT(1)R and << NF-κB >> p65 in the brain were also attenuated by [[ pranlukast ]]."", can you determine the relation? indirect-downregulator Regarding ""G6pc2 deletion resulted in a leftward shift in the dose-response curve for << glucose >>-stimulated [[ insulin ]] secretion (GSIS)."", can you determine the relation? upregulator Regarding ""The involvement of the various DA receptor subtypes in the motor effects of N/OFQ and NOP receptor antagonists was evaluated pharmacologically, using D1/D5 (SCH23390), D2/<< D3 >> (raclopride, [[ amisulpride ]]) and D3 (S33084) receptor antagonists, and by using D2 receptor knockout mice."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 196,"Question: What is the relation in the sentence ""Prednisolone also inhibited ACTH and << cortisol >> secretion in response to exogenous [[ CRH ]] stimulation, inferring rapid feedback inhibition at the anterior pituitary.""? product-of Question: What is the relation in the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Synergistic cytotoxicity was demonstrated, and << pemetrexed >> significantly decreased the amount of phosphorylated Akt, enhanced apoptosis, and increased the expression of dCK in A549 and Calu-6 cells, as well as the expression of the human nucleoside equilibrative transporter 1 ([[ hENT1 ]]) in all cell lines.""? indirect-upregulator Question: What is the relation in the sentence ""Suppression of Src/<< ERK >> and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells.""? downregulator Question: What is the relation in the sentence ""Additionally, << dasatinib >> leads to growth inhibition of a [[ KIT ]]D816V-harboring human masto-cytosis cell line.""? inhibitor Question: What is the relation in the sentence ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively.""? upregulator Question: What is the relation in the sentence ""In conclusion, the production of IL-4 and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by << DEX >> than that of [[ IFN-gamma ]], which may account for the therapeutic effects of glucocorticosteroids in patients with asthma.""? indirect-downregulator Question: What is the relation in the sentence ""Clinical effects of << pranlukast >>, an oral [[ leukotriene receptor ]] antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial.""? antagonist Question: What is the relation in the sentence ""We confirm the correlation between higher << hCTR1 >> levels and higher [[ Pt ]]-drug uptake in tumor cells sensitive to the drug.""? substrate Question: What is the relation in the sentence ""The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific).""? agonist Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""Polymorphisms in dopamine transporter (<< SLC6A3 >>) are associated with stimulant effects of [[ D-amphetamine ]]: an exploratory pharmacogenetic study using healthy volunteers.""? activator Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""Direct transport of << rifampicin >> could be shown for OATP-C (apparent K(m) value 13 micromol/L) and [[ OATP8 ]] (2.3 micromol/L).""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 197,"Question: What is the relation in the sentence ""First, addition of << apolipoprotein A-I >> (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner.""? product-of Question: What is the relation in the sentence ""<< Carvedilol >> reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and [[ adrenomedullin ]].""? indirect-downregulator Question: What is the relation in the sentence ""To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, sodium hydrosulphide (<< NaHS >>), (10, 50 and 100 muM), that resulted in a significant increase in [[ SP ]] concentration and expression of PPT-A and NK1-R in acinar cells.""? indirect-upregulator Question: What is the relation in the sentence ""Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective << alpha(1A)-adrenoceptor >> antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).""? agonist Question: What is the relation in the sentence ""CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.""? upregulator Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates [[ tuberin ]] and activates mTOR.""? downregulator Question: What is the relation in the sentence ""<< Indomethacin >> completely antagonizes [[ CA ]] activity, i.e. abolishes the inhibitory effect of acetazolamide on CA.""? activator Question: What is the relation in the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].""? agonist-activator Question: What is the relation in the sentence ""PURPOSE: To compare << phenelzine >> (PLZ), an antidepressant drug with anxiolytic properties which inhibits [[ monoamine oxidase ]] (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).""? inhibitor Question: What is the relation in the sentence ""Polyclonal antisera to either << b5R >> or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl ([[ NHOH-4-ABP ]]) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP).""? substrate Question: What is the relation in the sentence ""Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists.""? antagonist Question: What is the relation in the sentence ""mRNA levels for RAR-alpha, << RAR-beta >> and RAR-gamma, the nuclear receptors for retinoic acid, decreased during activation of freshly isolated HSC even with [[ retinoid ]] supplementation.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 198,"An amphiphile with branched << poly(ethylene glycol) >> architecture also activated the [[ lectin ]] pathway but only through L-ficolin recognition. Question: what is the relation? Answer: activator Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats. Question: what is the relation? Answer: upregulator Density functional theory calculations using the hybrid functional B3LYP have been performed to study the << methyl >> transfer step in [[ glycine N-methyltransferase ]] (GNMT). Question: what is the relation? Answer: substrate << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Question: what is the relation? Answer: substrate_product-of The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B ([[ NF-κB ]]) genes expression in cisplatin injected rats. Question: what is the relation? Answer: indirect-upregulator These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of [[ VEGF ]]and MMP-9, resulting from the inhibition of Akt pathway. Question: what is the relation? Answer: downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure. Question: what is the relation? Answer: agonist The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Question: what is the relation? Answer: agonist-activator In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), [[ interleukin-6 ]] (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells. Question: what is the relation? Answer: indirect-downregulator Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS. Question: what is the relation? Answer: product-of A novel class of << quinoxalines >> has been discovered as antagonists of the [[ IgG ]]:FcRn protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen. Question: what is the relation? Answer: antagonist We describe the discovery of several << pyrrolopyrazines >> as potent and selective [[ Syk ]] inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Question: what is the relation? Answer: inhibitor Hydrogen sulfide (H(2)S), a regulatory gaseous molecule that is endogenously synthesized by << cystathionine gamma-lyase >> (CSE) and/or cystathionine beta-synthase (CBS) from [[ L-cysteine ]] (L-Cys) metabolism, is a putative vasodilator, and its role in nitric oxide (NO) production is unexplored. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 199,"Given the text ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity."", describe the relation. downregulator Given the text ""In this study, using reverse transcriptase PCR (RT-PCR) and ELISA, we showed that << TCDD >> up-regulated the expression and secretion of tumor necrosis factor-alpha ([[ TNF-α ]]) in a time-dependent manner in cultured HAPI microglial cells."", describe the relation. indirect-upregulator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", describe the relation. substrate_product-of Given the text ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues."", describe the relation. product-of Given the text ""Moreover, GCs have a synergistic effect on << GW4064 >>-induced [[ FXR ]] activation, whereas chenodeoxycholate and GW4064 have an additive effect."", describe the relation. activator Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""In contrast, the selective << beta2AR >> antagonists ICI-118,551 and butoxamine inhibited [[ isoproterenol ]]-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively)."", describe the relation. agonist Given the text ""A series of phenolic acids and << phenol >> natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1)."", describe the relation. inhibitor Given the text ""<< CGP 12177A >> mediates cardiostimulation by activation of the 'putative' beta(4)-adrenoceptor; however, it has recently been reported that disruption of the [[ beta(1)-adrenoceptor ]] gene abolishes this effect."", describe the relation. upregulator Given the text ""<< Pinosylvin >> was also found to attenuate the activation of proteins involved in f[[ ocal adhesion kinase ]] (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway."", describe the relation. indirect-downregulator Given the text ""Inhibition of binding of the alpha2-receptor antagonist << [3H]RX821002 >> to recombinant [[ alpha2-receptors ]] by etomidate was tested in human embryonic kidney (HEK293) cells in vitro."", describe the relation. antagonist Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""Despite the importance of << AKRs >> in [[ PAHs ]] metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs)."", describe the relation. substrate Given the text ""This activity, like << NQO1 >>, was inhibited by [[ dicoumarol ]] and immunologically related to NQO1."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 200,"Moreover, a normal level of expression of << PSS1 >> and/or PSS2 is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis. Question: what is the relation? Answer: product-of The positive correlation between << vitamin A >> and [[ immunoglobulin A ]] concentrations might be the result of the vitamin A inductive effect during immunoglobulins A synthesis. Question: what is the relation? Answer: upregulator BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific << alpha2-adrenoceptor >> agonists of the type such as [[ dexmedetomidine ]]. Question: what is the relation? Answer: agonist In combination with << clofarabine >>, the ability of resveratrol to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment. Question: what is the relation? Answer: downregulator << ALD >> increased calpain expression and [[ caspase-3 ]] activity and promoted Bid cleavage. Question: what is the relation? Answer: activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Local LC citalopram effect was abolished by LC presence of the 5-HT3 receptor antagonist MDL72222 (1 μM) but not the << 5-HT1/2 >> receptor antagonist [[ methiothepin ]] (1 μM). Question: what is the relation? Answer: antagonist The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo. Question: what is the relation? Answer: substrate As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to [[ metformin ]] or pioglitazone and was noninferior to glipizide when added to metformin. Question: what is the relation? Answer: indirect-upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and [[ catalase ]] (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system. Question: what is the relation? Answer: indirect-downregulator << Wogonoside >> also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase ([[ p70S6K) ]] by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway. Question: what is the relation? Answer: inhibitor In guinea-pig isolated colon, AS-8112 produced a rightward shift of the concentration-response curves of << 2-methyl-5HT >>, a [[ 5-HT3 receptor ]] agonist (pA2 value of 7.04). Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 201,"<< 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and [[ Nrf-2 ]]-dependent heme oxygenase-1 induction. what is the relation? activator In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. what is the relation? agonist-activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor << Zolmitriptan >> (Zomig; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura. what is the relation? agonist In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and [[ catalase ]] (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system. what is the relation? indirect-downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. what is the relation? substrate_product-of << Phenobarbital >> (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including erythropoietin, heme oxygenase-1 and [[ vascular endothelial growth factor-a ]]. what is the relation? indirect-upregulator EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists ONO-AE3-208 and [[ AH 23848 ]], inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth. what is the relation? antagonist << ACTH >>-stimulated peak cortisol, [[ delta cortisol ]], and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover. what is the relation? product-of Suppression of Src/ERK and << GSK-3 >>/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells. what is the relation? downregulator In addition, the disease activity index, histopathologic scores and << myeloperoxidase >> activity were also significantly reduced by [[ Fc11a-2 ]] treatment. what is the relation? inhibitor In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent << amino acid >> transporter, with functional features of [[ ASCT2 ]] transport. what is the relation? upregulator One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, << EC 2.1.2.1 >>) with glycine ([[ Gly ]]) as one-carbon (1-C) source. what is the relation? substrate Modulation of the function of CD36 (CD36-/- mice), p38(MAPK) (SB203580), << COX-1 >> ([[ indomethacin ]]), and glycoprotein Ib alpha (Nk-protease, 6D1 antibody) induced approximately 50% inhibition. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 202,"The << M564G >> mutated CrAT showed higher activity toward longer chain [[ acyl-CoAs ]]: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA. Query: What is the relation? substrate One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Query: What is the relation? substrate_product-of Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Query: What is the relation? upregulator Enalkiren (<< A-64662 >>), a potent, dipeptide [[ renin ]] inhibitor, mimics the transition state of the human renin substrate, angiotensinogen. Query: What is the relation? inhibitor << Methionine synthase reductase >> (MTRR) is an enzyme involved in the conversion of Hcy to [[ methionine ]]. Query: What is the relation? product-of The maximum stimulation of Cdx2 and << MUC2 >> mRNA induced by [[ CDCA ]] was observed at 3 h and by 6 h, respectively. Query: What is the relation? indirect-upregulator << Pranlukast >>, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from [[ leukotriene receptor ]] antagonism. Query: What is the relation? antagonist Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (ramelteon, << TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice. Query: What is the relation? agonist In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Query: What is the relation? agonist-activator << Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β ([[ GSK-3β ]]) signaling pathway. Query: What is the relation? indirect-downregulator A dose of 25 microg kg(-1) day(-1) of << formoterol >> elicited greater EDL and soleus hypertrophy than salmeterol, but resulted in similar [[ beta-adrenoceptor ]] downregulation. Query: What is the relation? downregulator << CGP 12177A >> mediates cardiostimulation by activation of the 'putative' [[ beta(4)-adrenoceptor ]]; however, it has recently been reported that disruption of the beta(1)-adrenoceptor gene abolishes this effect. Query: What is the relation? activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor SDH << (L-serine dehydratase >>, EC 4.3.1.17) catalyzes the pyridoxal 5'-phosphate (PLP)-dependent dehydration of [[ L-serine ]] to yield pyruvate and ammonia. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 203,"<< Amitriptyline >>, but not any other tricyclic or selective serotonin reuptake inhibitor antidepressants, promotes [[ TrkA ]] autophosphorylation in primary neurons and induces neurite outgrowth in PC12 cells. what is the relation? activator Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats. what is the relation? upregulator In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the [[ methyl CpG-binding proteins ]] (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. what is the relation? downregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. what is the relation? agonist-activator << Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase ([[ FAK ]])/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway. what is the relation? indirect-downregulator The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals. what is the relation? antagonist The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure. what is the relation? agonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Taken together, the data provide evidence that the synergistic antiproliferative effect of << resveratrol >> and clofarabine is linked to the inhibition of [[ Akt ]] and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma. what is the relation? inhibitor One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of << PGE(2) >> is synthesized from arachidonic acid by [[ cyclooxygenases ]] (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). what is the relation? product-of The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B ([[ NF-κB ]]) genes expression in cisplatin injected rats. what is the relation? indirect-upregulator The << CYP2B6*6 >> Allele Significantly Alters the N-demethylation of [[ Ketamine ]] Enantiomers In Vitro. what is the relation? substrate Induction of << HO-1 >> through p38 MAPK/Nrf2 signaling pathway by [[ ethanol ]] extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264.7 cells and CLP-induced septic mice. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 204,"<< Fluoride >> treatment also increased phosphorylation of [[ JNK ]] and ERK, but not p38, and apoptosis induced by fluoride was notably or partly suppressed by treatment with JNK or ERK inhibitors, respectively. Query: What is the relation? activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and [[ histamine ]]. Query: What is the relation? agonist The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator 6-DHSG was metabolised by GSH to form a GSH conjugate (<< GS-6-DHSG >>) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of [[ glutathione-S-transferase ]] (GST). Query: What is the relation? product-of It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of [[ I-κBε ]] and nuclear translocation of c-Rel/p50 in alveolar epithelial cells. Query: What is the relation? downregulator << Chlorpheniramine >> (10 microM), another [[ histamine H1 receptor ]] antagonist without significant 5-HT receptor binding affinity, did not produce any inhibition of the eNANC contraction. Query: What is the relation? antagonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of Transduction with constitutively active forms of GSK-3β could protect against the downregulation of << p65 >> and upregulation of cleaved-PARP that are induced by [[ cinobufagin ]] treatment. Query: What is the relation? indirect-downregulator Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin ([[ TCDD ]]), the most potent activator of AhR. Query: What is the relation? upregulator PURPOSE: The fluoropyrimidine carbamate (<< capecitabine >>) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues. Query: What is the relation? substrate Comparison of the monoamine oxidase inhibiting properties of two reversible and selective << monoamine oxidase-A >> inhibitors [[ moclobemide ]] and toloxatone, and assessment of their effect on psychometric performance in healthy subjects. Query: What is the relation? inhibitor << LTD4 >> also induced expression of cysteinyl leukotriene receptor 1 (CysLT(1)R) and NF-κB [[ p65 ]] in the hippocampus and cortex. Query: What is the relation? indirect-upregulator As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of << COX-2 >> than [[ phenylbutazone ]] and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 205,"They all expressed ASS, but not << ornithine transcarbamylase >> (OTC), the enzyme that converts [[ ornithine ]], the product of degradation of arginine with rhArg, to citrulline, which is converted back to arginine via ASS. Query: What is the relation? substrate The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure. Query: What is the relation? agonist Transduction with constitutively active forms of GSK-3β could protect against the downregulation of << p65 >> and upregulation of cleaved-PARP that are induced by [[ cinobufagin ]] treatment. Query: What is the relation? indirect-downregulator L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or [[ 2-oxobutyrate ]]. Query: What is the relation? product-of Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. Query: What is the relation? antagonist << PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as [[ p21 ]] and p27. Query: What is the relation? indirect-upregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Query: What is the relation? upregulator Conversely, << AMPK >> inhibitor [[ compound C ]] or GSK3β inhibitor SB216763 blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells. Query: What is the relation? inhibitor Treatment of C57 BL/6 mice with << bleomycin >> increased fibroblast viability and collagen production and significantly downregulated [[ Nrf2 ]]. Query: What is the relation? downregulator Taken together, these findings indicate that << antofine >> induces Cx43 gap junction disassembly by the [[ PKCβ ]] signaling pathway. Query: What is the relation? activator Inhibition of << 5-lipoxygenase >> pathway of arachidonic acid metabolism in human neutrophils by [[ sulfasalazine ]] and 5-aminosalicylic acid. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 206,"The << A2A adenosine receptor >> agonist [[ CGS21680 ]] (C23H29N7O6.HCl.xH2O) (0.001-0.1 μM) did not alter NE oxidation currents. Question: what is the relation? Answer: agonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor Further, 5HHMF increased specific DNA-binding activity of << Nrf2 >>, and transient knockdown with Nrf2 siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. Question: what is the relation? Answer: upregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Question: what is the relation? Answer: substrate_product-of Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. Question: what is the relation? Answer: product-of Subsequent analysis revealed that << cucurbitacin I >> strongly activates RhoA and the [[ Rho ]] effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers. Question: what is the relation? Answer: activator The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Question: what is the relation? Answer: agonist-activator In the present study, we compared the pharmacology of (+/-)pindolol, << WAY-100635 >> (a [[ 5-HT(1A) ]] antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. Question: what is the relation? Answer: antagonist Treatment with << carvedilol >> reversed both protein and mRNA of HIF-1alpha, VEGF, [[ BNP ]], and NGF-beta to the baseline values. Question: what is the relation? Answer: indirect-downregulator Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]. Question: what is the relation? Answer: downregulator Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced << butein >>-induced [[ HO-1 ]] expression, and butein treatment led to increased JNK phosphorylation. Question: what is the relation? Answer: indirect-upregulator << Cholesterol >> uptake from [[ lipoproteins ]], intracellular vesicle transport and lipid transfer are also modified by oxysterols. Question: what is the relation? Answer: substrate Four prenylflavonoids, << kurarinone >> ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase ([[ DGAT ]]). Question: what is the relation? Answer: inhibitor CK significantly inhibited << DMN >>-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and [[ collagen ]] content. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 207,"Question: What is the relation in the sentence ""<< Adenylosuccinate synthetase >> (AdSS) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP.""? product-of Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, << Rec 15/2739 >>, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].""? antagonist Question: What is the relation in the sentence ""In addition, << prunetin >> inhibits [[ NF-κB ]]-dependent inflammatory responses by modulating IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signaling.""? inhibitor Question: What is the relation in the sentence ""Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats.""? upregulator Question: What is the relation in the sentence ""Direct-acting << CB1 >> agonists, including [[ Δ(9)-tetrahydrocannabinol ]], WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.""? agonist Question: What is the relation in the sentence ""Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal NGF, BDNF and [[ ChAT ]] that was eliminated by olanzapine treatment.""? indirect-downregulator Question: What is the relation in the sentence ""<< Allicin >> treatment showed reduced production of pro-inflammatory cytokines and NO and increased [[ HO-1 ]] activity.""? activator Question: What is the relation in the sentence ""Crocin (25 and 50mg/kg) or << vitamin E >> improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of [[ caspase 3 ]] and release of cytochrome c to the cytosol induced by DZN.""? indirect-upregulator Question: What is the relation in the sentence ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).""? downregulator Question: What is the relation in the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons.""? agonist-activator Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Recombinant << PDE10A >> transfected and expressed in COS-7 cells hydrolyzed cAMP and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with [[ cGMP ]] was almost twice that with cAMP.""? substrate Question: What is the relation in the sentence ""In vivo, agonist actions of yohimbine at << 5-HT(1A) >> sites are revealed by [[ WAY100,635 ]]-reversible induction of hypothermia in the rat.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 208,"In reference to ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", what is the relation? agonist-activator In reference to ""The positive correlation between vitamin A and << immunoglobulin A >> concentrations might be the result of the [[ vitamin A ]] inductive effect during immunoglobulins A synthesis."", what is the relation? upregulator In reference to ""<< Wogonoside >> also suppressed the activation of mammalian target of rapamycin ([[ mTOR ]]) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway."", what is the relation? inhibitor In reference to ""Similar to gemfibrozil, << clofibrate >>, another fibrate drug, also inhibited the expression of [[ iNOS ]]."", what is the relation? indirect-downregulator In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Pre-clinical pharmacology of << zolmitriptan >> (Zomig; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine."", what is the relation? agonist In reference to ""RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than [[ COX-1 ]] (IC(50) = 0.210 microM)."", what is the relation? downregulator In reference to ""Exogenous << C2-ceramide >> activates [[ c-fos serum response element ]] via Rac-dependent signalling pathway."", what is the relation? activator In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""<< Mitochondrial arginase II >> modulates [[ nitric-oxide ]] synthesis through nonfreely exchangeable L-arginine pools in human endothelial cells."", what is the relation? product-of In reference to ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of << L-glutamic acid >> for [[ aminopeptidase A ]] and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B."", what is the relation? substrate In reference to ""Prazosin (nonselective alpha(1)-adrenoceptor antagonist), << silodosin >> (selective [[ alpha(1A)-adrenoceptor ]] antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively)."", what is the relation? antagonist In reference to ""Altogether, our findings support a model in which Top2β deficiency promotes << CPT >>-induced apoptosis in quiescent non-S-phase cells, possibly due to RNAP LS depletion and [[ p53 ]] accumulation."", what is the relation? indirect-upregulator In reference to ""We report here the pharmacological properties of a third selective COX-2 inhibitor, << valdecoxib >>, which is the most potent and in vitro selective of the marketed [[ COX-2 ]] inhibitors that we have studied."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 209,"Question: What is the relation in the sentence ""In addition to this pronounced loss of function, << M1766L >> also showed a 10-fold increase in the persistent late [[ sodium ]] current.""? upregulator Question: What is the relation in the sentence ""While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of [[ H1-receptor ]] antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity.""? agonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity.""? agonist-activator Question: What is the relation in the sentence ""In addition, << ethanol >> induced degradation of [[ DNA methyltransferases ]] (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway.""? downregulator Question: What is the relation in the sentence ""<< Rofecoxib >> only diminished [[ COX-2 ]] protein expression and MCP-1 gene expression in vascular atheroma.""? indirect-downregulator Question: What is the relation in the sentence ""Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, << HDC >> activity and HDC mRNA induced by [[ TDI ]] in TDI-sensitized rats.""? activator Question: What is the relation in the sentence ""In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(V)1.5 << sodium channels >>[[ sodium ]] channels expressed in Chinese Hamster Ovary (CHO-K1) cells.""? substrate Question: What is the relation in the sentence ""<< CDCA >> induced dose-dependent expression of Cdx2 and [[ MUC2 ]] at both the mRNA and protein levels.""? indirect-upregulator Question: What is the relation in the sentence ""Taken together, our findings indicate that << 5HHMF >> suppresses NO production through modulation of iNOS, consequently suppressing [[ NF-κB ]] activity and induction of Nrf2-dependent HO-1 activity.""? inhibitor Question: What is the relation in the sentence ""We also shortly discuss the ongoing debate on whether << NO >> is the actual reaction product of [[ NOS ]] catalysis, as well as the phenomenon of NO-mediated autoinhibition.""? product-of Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an [[ N-methyl d-aspartate receptor ]] (NMDAR) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting.""? antagonist Question: What is the relation in the sentence ""The binding of FHA-HIS was inhibited on 35-79% of the platelets by the << histamine H1 receptor >> antagonists diphenhydramine and [[ clemastine ]].""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 210,"<< Leukotriene D4 >> induces cognitive impairment through enhancement of CysLT₁ R-mediated [[ amyloid-β ]] generation in mice. Query: What is the relation? indirect-upregulator << Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/[[ extracellular signal-regulated kinase ]] (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway. Query: What is the relation? indirect-downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Query: What is the relation? substrate_product-of RGM-1 cells were treated with CDCA or << GW4064 >>, an [[ FXR ]] agonist, in the presence or absence of guggulsterone, an FXR antagonist. Query: What is the relation? agonist Interestingly, disruption of the RhoA-ROCK pathway prevented the inhibitory effect of << cucurbitacin I >> on [[ Rac1 ]] activation by heregulin. Query: What is the relation? inhibitor << PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate ([[ PMA ]]) in WEHI-231, HOP-92, and Colo-205 cells. Query: What is the relation? downregulator Role of << organic cation/carnitine transporter 1 >> in uptake of [[ phenformin ]] and inhibitory effect on complex I respiration in mitochondria. Query: What is the relation? substrate The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II. Query: What is the relation? product-of In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor << Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity. Query: What is the relation? upregulator << GW9662 >>, a [[ PPARgamma ]] antagonist, prevented (P < 0.01) the lutein-induced iNOS mRNA downregulation in HD11 cells. Query: What is the relation? antagonist << 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to [[ TSC2 ]]. Query: What is the relation? activator IKM-159 was developed and identified as a member of a new class of heterotricyclic << glutamate >> analogues that act as [[ AMPA receptor ]]-selective antagonists. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 211,"Regarding ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", can you determine the relation? agonist-activator Regarding ""The effect of sumatriptan, but not of LY 344864, was prevented by pretreatment with the antagonist << SDZ 21-009 >>, which displays high affinity for [[ rat 5-HT1B ]] receptors."", can you determine the relation? antagonist Regarding ""Thus, << sorafenib >> may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of [[ Raf ]] and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling)."", can you determine the relation? indirect-downregulator Regarding ""Coexpression of GRK2 or GRK2 and arrestin-2 permitted << etorphine >> to induce down-regulation of the [[ hkor ]], although expression of arrestin-2 or dynamin I alone did not."", can you determine the relation? downregulator Regarding ""Cycloxygenase-2 (<< COX-2 >>)-derived prostaglandin E2 ([[ PGE2 ]]) has been shown to be important in esophageal tumorigenesis."", can you determine the relation? product-of Regarding ""In conclusion, << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist timolol."", can you determine the relation? activator Regarding ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats."", can you determine the relation? upregulator Regarding ""Adenosine and << N(6)-cyclopentyl-adenosine >> (CPA, [[ A1R ]] agonist) constricted MVs but not MAs."", can you determine the relation? agonist Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""Furthermore, the up-regulation of << IL-12 >> and TNF-α was found in the [[ procyanidin ]] trimers-treated cells in the presence of OVA."", can you determine the relation? indirect-upregulator Regarding ""Inhibition of << mTOR >> by small dose of [[ rapamycin ]] reduces podocyte apoptosis, attenuates glomerular injury and albuminuria."", can you determine the relation? inhibitor Regarding ""<< Omega class GSTs >> have dehydroascorbate reductase and thioltransferase activities and also catalyze the reduction of [[ monomethylarsonate ]], an intermediate in the pathway of arsenic biotransformation."", can you determine the relation? substrate Regarding ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""<< SB203580 >> (a specific inhibitor of p38 [[ kinase ]]) markedly suppressed the increased expression of collagen type I and α-SMA in TGF-β1-induced NPDFs."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 212,"Licofelone almost abolished << 5-LOX >> activity by inhibiting [[ leukotriene B4 ]] generation in rabbit neutrophils and prevented platelet thromboxane B2 production from whole blood. Query: What is the relation? product-of Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity. Query: What is the relation? upregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor CONCLUSION: A long-term intake of << ethanol >> solution down-regulates the phosphorylation of [[ CREB ]] in the nucleus accumbens, and those changes can be reversed by naloxone, which may be one kind of the molecular mechanisms associated with ethanol dependence. Query: What is the relation? downregulator UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and UDP-<< glucuronic acid >> than the other [[ UGTs ]]. Query: What is the relation? substrate << AhR >>-dependent reporter gene expression in transfected HepG2 cells was increased by [[ pelargonidin ]] in a concentration-dependent manner at 24h. Query: What is the relation? indirect-upregulator Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and [[ mTOR ]] via suppression of Ras prenylation and enhanced Bim expression. Query: What is the relation? indirect-downregulator << ALD >> increased calpain expression and [[ caspase-3 ]] activity and promoted Bid cleavage. Query: What is the relation? activator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Query: What is the relation? substrate_product-of << Memantine >> is an uncompetitive (channel blocking) [[ NMDA receptor ]] antagonist. Query: What is the relation? antagonist The effects of the << adenosine A3 receptor >> agonist [[ IB-MECA ]] on sodium taurocholate-induced experimental acute pancreatitis. Query: What is the relation? agonist Nitrogen-containing bisphosphonates (N-<< BPs >>) induce apoptosis in tumor cells by inhibiting the prenylation of small [[ G-proteins ]]. Query: What is the relation? inhibitor Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, [[ acenaphthylene ]], naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 213,"Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""<< Fluoride >> treatment also increased phosphorylation of [[ JNK ]] and ERK, but not p38, and apoptosis induced by fluoride was notably or partly suppressed by treatment with JNK or ERK inhibitors, respectively."", what is the relation? activator Regarding the sentence ""Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory [[ cytokines ]], increased adiponectin expression and improved glucose tolerance parallel to insulin sensitivity in obese mice."", what is the relation? indirect-downregulator Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""<< Prednisolone >> also inhibited ACTH and cortisol secretion in response to exogenous [[ CRH ]] stimulation, inferring rapid feedback inhibition at the anterior pituitary."", what is the relation? downregulator Regarding the sentence ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity."", what is the relation? upregulator Regarding the sentence ""The << BH(4) >> treatment also partially improved the [[ insulin ]] sensitivity and blood pressure, as well as the serum triglyceride concentration, in the fructose-fed rats."", what is the relation? indirect-upregulator Regarding the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator Regarding the sentence ""<< TAS-102 >> is a novel drug containing trifluorothymidine, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS."", what is the relation? substrate Regarding the sentence ""Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II."", what is the relation? product-of Regarding the sentence ""The antagonistic property of << rilmenidine >> at [[ human alpha(2A)-adrenoceptors ]] indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved."", what is the relation? antagonist Regarding the sentence ""Together, this pharmacological profile of subtype-selective betaAR antagonists indicates that in this model, << beta1AR >> activation is responsible for the enhanced hippocampal CA3 network activity initiated by [[ isoproterenol ]]."", what is the relation? agonist Regarding the sentence ""Recent studies have reported that << imatinib mesylate >>, a kinase inhibitor that targets the intracellular [[ tyrosine kinase ]] BCR-ABL and the platelet derived growth factor (PDGF) receptor, is an effective inhibitor of the macrophage colony stimulating factor (M-CSF) receptor, c-FMS."", what is the relation? inhibitor Regarding the sentence ""Interestingly, there was a loss in the binding of ICAM2 to << actin >> during [[ CdCl₂ ]]-induced germ cell loss, suggesting that a loss of ICAM2-actin interactions might have facilitated junction restructuring."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 214,"Question: What is the relation in the sentence ""CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme.""? upregulator Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma.""? agonist-activator Question: What is the relation in the sentence ""Also, << SB365 >> showed anti-angiogenic activity by decreasing the expression of [[ HIF-1α ]] and VEGF.""? indirect-downregulator Question: What is the relation in the sentence ""Extracellular application of << meclofenamate >> (EC(50) = 25 microM) and diclofenac (EC(50) = 2.6 microM) resulted in the activation of [[ KCNQ2/Q3 ]] K(+) currents, heterologously expressed in Chinese hamster ovary cells.""? activator Question: What is the relation in the sentence ""One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (<< SHMT >>, EC 2.1.2.1) with [[ glycine ]] (Gly) as one-carbon (1-C) source.""? substrate Question: What is the relation in the sentence ""<< Glufosinate >> inhibits [[ glutamine synthetase ]] and blocks biosynthesis of glutamine.""? inhibitor Question: What is the relation in the sentence ""<< Prednisolone >> also inhibited ACTH and cortisol secretion in response to exogenous [[ CRH ]] stimulation, inferring rapid feedback inhibition at the anterior pituitary.""? downregulator Question: What is the relation in the sentence ""These data suggest that endothelial << NO >> synthesis depends on the activity of [[ arginase II ]] in mitochondria and l-arginine carriers in cell membrane.""? product-of Question: What is the relation in the sentence ""The potency of the antipsychotic drug, << risperidone >>, to antagonize alpha 1A-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and [[ alpha 1B-adrenoceptor ]]-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 1-adrenoceptor subtype-discriminating antagonists.""? antagonist Question: What is the relation in the sentence ""The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, [[ aspartate aminotransferase ]], alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).""? indirect-upregulator Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""One of the << CB2 >> agonists, [[ N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1,3,5-triazin-2-amine ]] (19, -logEC(50)=7.5, E(max)=255%) was selected for further development.""? agonist Question: What is the relation in the sentence ""<< Cabozantinib >> (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 ([[ VEGFR2 ]]), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 215,"<< SNP >> inhibits the accumulation of HIF-1alpha, the regulatory subunit of HIF-1, and the transcriptional activation of [[ HIF-1alpha ]] via a mechanism that is not dependent on either NO or soluble guanylate cyclase. Question: what is the relation? Answer: indirect-downregulator << COX-1 >> inhibition was measured as percentage inhibition of serum [[ TXB2 ]] generation in clotting whole blood, and as closure time with use of the platelet function analyser PFA-100. Question: what is the relation? Answer: product-of In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the [[ methyl CpG-binding proteins ]] (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Question: what is the relation? Answer: downregulator The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B ([[ NF-κB ]]) genes expression in cisplatin injected rats. Question: what is the relation? Answer: indirect-upregulator These protective effects were abolished by << glucocorticoid receptor >> (GR) antagonist [[ RU486 ]] or p-ERK inhibitor U0126 rather than estrogen receptor α antagonist ICI 82,780. Question: what is the relation? Answer: antagonist RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Question: what is the relation? Answer: agonist-activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor Based on recent reports that the small molecules, isatin and << phthalimide >>, are suitable scaffolds for the design of high potency [[ monoamine oxidase ]] (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues. Question: what is the relation? Answer: inhibitor Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed << 5-MeO-DMT >> metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-[[ CYP2D6 ]] mouse models. Question: what is the relation? Answer: substrate OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a [[ peroxisome proliferator-activated receptor alpha ]] (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent. Question: what is the relation? Answer: agonist The positive correlation between vitamin A and immunoglobulin A concentrations might be the result of the << vitamin A >> inductive effect during [[ immunoglobulins A ]] synthesis. Question: what is the relation? Answer: upregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Question: what is the relation? Answer: substrate_product-of << 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and Nrf-2-dependent [[ heme oxygenase-1 ]] induction. Question: what is the relation? Answer: activator Design, Synthesis, Biological Evaluation, and Docking Studies of << (S)-Phenylalanine >> Derivatives with a 2-Cyanopyrrolidine Moiety as Potent [[ Dipeptidyl Peptidase 4 ]] Inhibitors. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 216,"Consider the text ""Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing << GluR3 >>(L507Y) mutant, but has synergistic effects with [[ lithium ]] on wild-type receptors."". Can you identify the relation? activator Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""<< Choline dehydrogenase >> (CHDH) and betaine-homocysteine methyltransferase (BHMT) are 2 enzymes involved in [[ choline ]] oxidation."". Can you identify the relation? substrate Consider the text ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h."". Can you identify the relation? upregulator Consider the text ""Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers << DEX >> inhibited IL-2 production partially and enhanced [[ IL-2R alpha ]] expression and proliferation."". Can you identify the relation? indirect-upregulator Consider the text ""Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and [[ Dkk2 ]]) of the pathway."". Can you identify the relation? downregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""Together these studies support a unique mode of inhibition in which << phenothiazines >> disrupt the [[ S100A4 ]]/myosin-IIA interaction by sequestering S100A4 via small molecule-induced oligomerization."". Can you identify the relation? inhibitor Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""<< COX-1 >> inhibition was measured as percentage inhibition of serum [[ TXB2 ]] generation in clotting whole blood, and as closure time with use of the platelet function analyser PFA-100."". Can you identify the relation? product-of Consider the text ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]]."". Can you identify the relation? indirect-downregulator Consider the text ""<< Ambrisentan >> is an [[ endothelin type A (ET(A))-selective receptor ]] antagonist that is metabolized primarily by glucuronidation but also undergoes oxidative metabolism by CYP3A4."". Can you identify the relation? antagonist Consider the text ""Pre-clinical pharmacology of zolmitriptan (Zomig; formerly << 311C90 >>), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine."". Can you identify the relation? agonist Consider the text ""Potency switch between CHK1 and << MK2 >>: Discovery of imidazo[1,2-a]pyrazine- and [[ imidazo[1,2-c]pyrimidine ]]-based kinase inhibitors."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 217,"In reference to ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and << hydrogen peroxide >>) showed that the [[ aldo-keto reductase (AKR) 1C1 ]] is highly inducible by all treatments."", what is the relation? indirect-upregulator In reference to ""Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 ([[ hCES1 ]]) and 2 (hCES2)."", what is the relation? substrate In reference to ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice ([[ MSG ]], 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", what is the relation? downregulator In reference to ""In contrast, there was little change in mRNA levels for GTP cyclohydrolase I (<< GTPCH >>), the rate limiting enzyme in synthesis of the [[ tetrahydrobiopterin ]] (BH4), the obligate cofactor for TPH."", what is the relation? product-of In reference to ""These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in [[ cyclin E ]] and cdk2 kinase activities."", what is the relation? activator In reference to ""CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", what is the relation? upregulator In reference to ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""We then showed that static exposure of embryos to << paraoxon >> (31.2-500 nM) from 5 to 96 hpf resulted in significant stage- and concentration-dependent [[ AChE ]] inhibition, albeit these effects were fully reversible within 48 h following transfer to clean water."", what is the relation? inhibitor In reference to ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist [[ AM1241 ]] [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects."", what is the relation? agonist In reference to ""<< Catalpol >> also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of [[ IκBα ]] and the nuclear localization of NF-κB."", what is the relation? indirect-downregulator In reference to ""Combination treatment with the selective << 5-HT1A >> antagonist [[ WAY100635 ]] produced a dose-dependent augmentation of venlafaxine-induced (3-30 mg/kg s.c) extracellular 5-HT concentrations, but had no further effect on NA above that produced by venlafaxine alone."", what is the relation? antagonist In reference to ""A highly potent inhibition of the << peroxidase >> catalytic reaction by [[ NO ]]/SNO was seen in assays employing the coupled Prx-Trx system."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 218,"In reference to ""No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major [[ human cytochrome P450 ]] enzymes, inhibition of the biliary efflux transporters BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells."", what is the relation? inhibitor In reference to ""CONCLUSIONS: Our results show that << indomethacin >>, a known cyclooxygenase (COX) inhibitor, is also an activator of [[ CA ]]."", what is the relation? activator In reference to ""<< Nizatidine >> (LY139037), a selective [[ histamine H2-receptor ]] antagonist, is a potent inhibitor of gastric acid secretion."", what is the relation? antagonist In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""<< Carvedilol >> reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and [[ adrenomedullin ]]."", what is the relation? indirect-downregulator In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""<< Ramelteon >> (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin [[ MT(1) ]]/MT(2) receptor agonist."", what is the relation? agonist In reference to ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]]."", what is the relation? downregulator In reference to ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h."", what is the relation? upregulator In reference to ""Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II."", what is the relation? product-of In reference to ""The present study examined the effect of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), on << VMAT2 >> activity by measuring adenosine triphosphate-dependent [[ [(3)H]dopamine ]] uptake into synaptic vesicles prepared from rat striatum."", what is the relation? substrate In reference to ""Exposure to << PAHs >>, their metabolites, and ROS further increase [[ AKRs ]] isoform expression that may amplify oxidative damage."", what is the relation? indirect-upregulator In reference to ""Pranlukast, ketamine and edaravone decreased NMDA-induced injury; pranlukast (0.1 mg/kg) and << ketamine >> inhibited the upregulated expression of the [[ CysLT1 receptor ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 219,"Given the text ""Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes [[ arachidonic acids ]] to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on the cardiovascular system."", describe the relation. substrate Given the text ""<< GW9662 >>, a [[ PPARgamma ]] antagonist, prevented (P < 0.01) the lutein-induced iNOS mRNA downregulation in HD11 cells."", describe the relation. antagonist Given the text ""IRF3 activation induced by MyD88-independent signaling components, << TRIF >> and TBK1, was also downregulated by [[ auranofin ]]."", describe the relation. indirect-downregulator Given the text ""We previously employed a chemical genomic strategy to identify a novel small molecule, << MAC13243 >>, as a likely inhibitor of the [[ bacterial lipoprotein ]] targeting chaperone, LolA."", describe the relation. inhibitor Given the text ""These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and << oxymetazoline >>-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates."", describe the relation. agonist Given the text ""CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", describe the relation. upregulator Given the text ""Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system."", describe the relation. product-of Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to << NRF2 >> inducers ([[ sulforaphane ]], tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."", describe the relation. activator Given the text ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and [[ MBD-3 ]]), in MEF cells by the proteasomal pathway."", describe the relation. downregulator Given the text ""<< Phenobarbital >> (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including [[ erythropoietin ]], heme oxygenase-1 and vascular endothelial growth factor-a."", describe the relation. indirect-upregulator Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""As discussed in this review, various << progestogens >> including dydrogesterone and its 20alpha-dihydro-derivative, medrogestone, promegestone, nomegestrol acetate and norelgestromin can reduce intratissular levels of estradiol in breast cancer by blocking [[ sulfatase ]] and 17beta-hydroxysteroid-dehydrogenase type 1 activities."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 220,"Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""EP(1) and << EP(3) receptor >> antagonists ONO-8713 and [[ ONO-AE3-240 ]], but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."". Can you identify the relation? antagonist Consider the text ""<< Catecholamines >> (adrenaline, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase ([[ phenylalanine hydroxylase ]], EC 1.14.16.1)."". Can you identify the relation? inhibitor Consider the text ""Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II."". Can you identify the relation? substrate Consider the text ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats."". Can you identify the relation? upregulator Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while << TDCPP >> induced CYP3A37 and [[ CYP2H1 ]]."". Can you identify the relation? indirect-upregulator Consider the text ""Polymorphisms in dopamine transporter (<< SLC6A3 >>) are associated with stimulant effects of [[ D-amphetamine ]]: an exploratory pharmacogenetic study using healthy volunteers."". Can you identify the relation? activator Consider the text ""Similar to gemfibrozil, clofibrate, another << fibrate >> drug, also inhibited the expression of [[ iNOS ]]."". Can you identify the relation? indirect-downregulator Consider the text ""In addition, cells pre-treated with DL-propargylglycine (PAG, 3 mM), a CSE inhibitor, reduced the formation of H(2)S in caerulein treated cells, suggesting that << CSE >> may be the main enzyme involved in [[ H(2)S ]] formation in mouse acinar cells."". Can you identify the relation? product-of Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""CONCLUSION: A long-term intake of << ethanol >> solution down-regulates the phosphorylation of [[ CREB ]] in the nucleus accumbens, and those changes can be reversed by naloxone, which may be one kind of the molecular mechanisms associated with ethanol dependence."". Can you identify the relation? downregulator Consider the text ""<< Ramelteon >> (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin [[ MT(1) ]]/MT(2) receptor agonist."". Can you identify the relation? agonist Consider the text ""Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by << quercetin >> through [[ HO-1 ]] induction."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",6,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",upregulator 221,"Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Adenylosuccinate synthetase (<< AdSS >>) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP."". Can you identify the relation? product-of Consider the text ""Firstly, transgenic plants overexpressing formate dehydrogenase (FDH, EC 1.2.1.2) were used to continue our previous studies on the function of << FDH >> in [[ formate ]] metabolism."". Can you identify the relation? substrate Consider the text ""Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats."". Can you identify the relation? upregulator Consider the text ""Thus, << amitriptyline >> acts as a TrkA and [[ TrkB ]] agonist and possesses marked neurotrophic activity."". Can you identify the relation? agonist Consider the text ""<< Cobalt chloride >>, a typical HIF activator, induced the gene expression of CAR-target genes, including [[ cyp2b9 ]] and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver."". Can you identify the relation? indirect-upregulator Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""In the present study, we compared the pharmacology of << (+/-)pindolol >>, WAY-100635 (a [[ 5-HT(1A) ]] antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat."". Can you identify the relation? antagonist Consider the text ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."". Can you identify the relation? downregulator Consider the text ""Everolimus (RAD001, << Afinitor((R)) Novartis >>) is the first oral inhibitor of [[ mTOR ]] (mammalian target of rapamycin) to reach the oncology clinic."". Can you identify the relation? inhibitor Consider the text ""The inhibition of << UG >> synthesis and PR down-regulation by 5 alpha-NET and [[ 3 beta,5 alpha-NET ]] indicates that these NET metabolites possess antiprogestational properties."". Can you identify the relation? indirect-downregulator Consider the text ""Since gemfibrozil is known to activate peroxisome proliferator-activated receptor-alpha (PPAR-alpha), we investigated the role of << PPAR-alpha >> in [[ gemfibrozil ]]-mediated inhibition of iNOS."". Can you identify the relation? activator Consider the text ""CONCLUSIONS AND IMPLICATIONS: Together, these data suggest that << thiocolchicoside >> significantly suppressed osteoclastogenesis induced by [[ RANKL ]] and tumour cells via the NF-kappaB signalling pathway."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 222,"Also in contrast to effects of multiple << METH >> injections, 1) MDMA caused little or no decrease in binding of the [[ DAT ]] ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal DA transport. what is the relation? downregulator In the present study, we compared the pharmacology of << (+/-)pindolol >>, WAY-100635 (a [[ 5-HT(1A) ]] antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. what is the relation? antagonist Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and [[ prostate-specific antigen ]] (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT). what is the relation? indirect-downregulator Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam (<< MDZ >>) as an inducer and a substrate to [[ CYP3A ]], respectively. what is the relation? substrate One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]. what is the relation? upregulator << PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases ([[ COX ]]) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). what is the relation? product-of The activity of polymerases containing mutations known to confer resistance to foscarnet (V715M, T700A and N495K) was inhibited by concentrations of << foscarnet >> eight to 14 times higher than those required to inhibit wild-type [[ polymerases ]]. what is the relation? inhibitor Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Sulfhydration of << sulfonylurea receptor 2B >> (SUR2B) was induced by [[ NaHS ]] and colonic inflammation. what is the relation? activator << V(5+) >> also increased serum hemoglobin ([[ Hb ]]) levels in animals treated for 24 h. what is the relation? indirect-upregulator << P2Y(2) receptor >> agonist [[ INS37217 ]] enhances functional recovery after detachment caused by subretinal injection in normal and rds mice. what is the relation? agonist << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. what is the relation? agonist-activator mRNA levels of << receptor activator of nuclear factor kappa-B >> (RANK), its ligand RANKL, tumor necrosis factor alpha (TNF-α) and RANKL/osteoprotegerin (OPG) ratio were diminished in the periodontium of CCL3(-/-) mice and in the group treated with [[ Met ]]-RANTES. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 223,"Given the text ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", describe the relation. agonist-activator Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", describe the relation. substrate_product-of Given the text ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", describe the relation. upregulator Given the text ""We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (<< 4-ABP >>; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5."", describe the relation. substrate Given the text ""When << amiloride >> was dropped on the eye surface on the first day of irradiation and subsequently daily until the end of the experiment, [[ u-PA ]] activity in both cornea and tear fluid was strongly inhibited."", describe the relation. inhibitor Given the text ""<< Adrenaline >> inhibits [[ insulin ]] secretion via pertussis toxin-sensitive mechanisms."", describe the relation. indirect-downregulator Given the text ""In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the << dopamine D2 >> agonist [[ apomorphine ]]; however, it is not clear whether both findings share the same biological basis."", describe the relation. agonist Given the text ""These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and [[ cdk2 ]] kinase activities."", describe the relation. activator Given the text ""<< Methionine synthase reductase >> (MTRR) is an enzyme involved in the conversion of Hcy to [[ methionine ]]."", describe the relation. product-of Given the text ""Conversely, AMPK inhibitor compound C or GSK3β inhibitor SB216763 blocked the cleavages of << PARP >> and caspase 3 induced by [[ ursolic acid ]] in HepG2 cells."", describe the relation. indirect-upregulator Given the text ""The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the << 5-HT(2A) >>-receptor antagonist [[ ketanserin ]] was without effect."", describe the relation. antagonist Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity."", describe the relation. downregulator Given the text ""6 In conclusion, << HERG >> channel inhibition by [[ cisapride ]] exhibits features consistent with open and inactivated state binding and is sensitive to external potassium concentration."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 224,"In further evaluation, the representative compound << N,N-diethyl-N-(2-(N-methyltetradecanamido)ethyl)prop-2-en-1-aminium bromide >> (3b) exhibited potent pro-apoptotic activity, through [[ RhoB ]] activation, in HeLa cells. what is the relation? activator One of the enzymes responsible for the production of << KA >>, kynurenine aminotransferase I ([[ KATI ]]), also catalyses the reversible transamination of glutamine to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? product-of OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (<< AR >>) agonist ([[ dexmedetomidine ]]). what is the relation? agonist The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, [[ albumin ]], bilirubin, cholesterol, urea and creatinine). what is the relation? indirect-upregulator Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). what is the relation? upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of << Sildenafil >> is inhibitory of PDE5 at a rate tenfold higher than for the next [[ PDE ]] (PDE6), which produces visual changes through the retinal rods. what is the relation? inhibitor In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. what is the relation? agonist-activator Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin. what is the relation? downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor << Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α ([[ TNF-α ]]), inducible NO synthase (iNOS), and receptor for AGE (RAGE). what is the relation? indirect-downregulator << Plerixafor >>, a [[ CXCR4 ]] antagonist for the mobilization of hematopoietic stem cells. what is the relation? antagonist Therefore, pretreatment tumor gene expression profiling of ASS and OTC could aid in predicting tumor response to << arginine >> depletion with [[ arginine-depleting enzymes ]]. what is the relation? substrate Expressions of insulin and << PC3 >>, but not PC2, are coordinately regulated by [[ glucose ]], consistent with the important role of PC3 in regulating proinsulin processing. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 225,"Consider the text ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and << AH 6809 >> (EP1 and [[ EP2 ]] specific)."". Can you identify the relation? antagonist Consider the text ""<< Cadmium >> activates [[ NADPH oxidase ]]."". Can you identify the relation? activator Consider the text ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, << cinnamic aldehyde >>, and hydrogen peroxide) showed that the [[ aldo-keto reductase (AKR) 1C1 ]] is highly inducible by all treatments."". Can you identify the relation? indirect-upregulator Consider the text ""The sympathetic nerves of both the human atrial appendages and rabbit pulmonary artery are endowed with << alpha(2A)-autoreceptors >>, at which, however, both rilmenidine and [[ oxymetazoline ]] exhibit different properties (antagonism and agonism, respectively)."". Can you identify the relation? agonist Consider the text ""A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, << gallic acid >>, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]])."". Can you identify the relation? inhibitor Consider the text ""<< Dexamethasone >> suppresses histamine synthesis by repressing both transcription and activity of [[ HDC ]] in allergic rats."". Can you identify the relation? indirect-downregulator Consider the text ""Moreover, a normal level of expression of PSS1 and/or << PSS2 >> is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis."". Can you identify the relation? product-of Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512)."". Can you identify the relation? upregulator Consider the text ""The discovery of an inducible << oxidase >> whose apparent substrate preference is [[ spermine ]] indicates that polyamine catabolism is more complex than that originally proposed."". Can you identify the relation? substrate Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and [[ retinoblastoma protein ]] (pRb), and the upregulation of p21(WAF1/CIP1) and p53."". Can you identify the relation? downregulator Consider the text ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""Elevated extracellular << D-glucose >> increases [[ transforming growth factor beta1 ]] (TGF-beta1) release from human umbilical vein endothelium (HUVEC)."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 226,"Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues. Please explain the relation. product-of A series of phenolic acids and phenol natural products, such as << p-hydroxybenzoic acid >>, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1). Please explain the relation. inhibitor Results showed that neonatal << quinpirole >> treatment induced [[ D2 ]] priming that was eliminated by olanzapine treatment. Please explain the relation. indirect-upregulator CONCLUSIONS: In the maximum registered dosage, << nabumetone >> inhibits thromboxane production much more than meloxicam, signifying less [[ COX-2 ]] selectivity of the former. Please explain the relation. downregulator Both risperidone and << 9-hydroxyrisperidone >> are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination. Please explain the relation. substrate On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]]. Please explain the relation. upregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and << sulprostone >> (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. Please explain the relation. indirect-downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. [[ alfuzosin ]], doxazosin, prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials. Please explain the relation. antagonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of Activation of endogenous << somatostatin receptor subtype 2 >> (sst2) by [[ somatostatin-14 ]] or activation of transiently transfected rat D2 dopamine receptors (rD2(long)) by quinpirole had no effect. Please explain the relation. activator While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early [[ H1-receptor ]] antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity. Please explain the relation. agonist These results are consistent with the interpretation that both piriprost and diethylcarbamazine inhibit leukotriene formation but that they act on sequential steps in the biosynthetic pathway in such a manner as to synergistically interfere with the availability or utilization of << LTA4 >> in the [[ leukotriene C synthetase ]] reaction. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 227,"We found that reduction of the carcinogenic hydroxylamines of the aromatic amine << 4-aminobiphenyl >> (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only [[ human b5R ]] and cyt b5. Query: What is the relation? substrate CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme. Query: What is the relation? upregulator METHODS: << Cyclooxygenase >> activity and selectivity was determined in vitro by measuring prostaglandin E(2) ([[ PGE(2) ]]) production following incubation of varying concentrations of NSAID with human recombinant COX-1 or COX-2 and arachidonic acid. Query: What is the relation? product-of Meanwhile, the serum level of KC (a functional homolog of << IL-8 >> and the main proinflammatory alpha chemokine in mice) in apoE(-/-) mice was up to 357pg/ml in [[ SFO ]]-HD treated group. Query: What is the relation? indirect-upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Query: What is the relation? substrate_product-of Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Query: What is the relation? agonist-activator The effect was counteracted by the << D(2) >> antagonist [[ eticlopride ]], pertussis toxin, the inhibitor of intracellular Ca(2+) release TMB-8, incubation in Ca(2+)-free experimental medium, and PKC desensitization obtained by chronic pretreatment with the phorbol ester TPA. Query: What is the relation? antagonist One of the mechanism of << mifepristone >> action on decreasing leiomyomata volume may be related to suppression on expression of [[ PR gene ]]. Query: What is the relation? indirect-downregulator The acetylcholinesterase (<< AChE >>) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine ]] (16) are described. Query: What is the relation? inhibitor These results indicate that << phenobarbital >> treatment induces [[ KCNK1 ]] to elicit a male-specific and growth-suppressing signal. Query: What is the relation? activator Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the [[ MDMA ]]-induced reduction in plasmalemmal DA transport. Query: What is the relation? downregulator Zolmitriptan (<< Zomig >>; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura. Query: What is the relation? agonist Acetyl-coenzyme A carboxylase (<< ACC >>) enzymes exist as two isoforms, ACC1 and ACC2, which play critical roles in [[ fatty acid ]] biosynthesis and oxidation. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 228,"Consider the text ""Expression of the dominant negative mutants rab5A-<< N133I >> or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation."". Can you identify the relation? downregulator Consider the text ""These data suggest that endothelial << NO >> synthesis depends on the activity of [[ arginase II ]] in mitochondria and l-arginine carriers in cell membrane."". Can you identify the relation? product-of Consider the text ""Inhibition of << mTOR >> by low dose [[ rapamycin ]] decreases HG-induced Nox4 and Nox1, NADPH oxidase activity and podocyte apoptosis."". Can you identify the relation? inhibitor Consider the text ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."". Can you identify the relation? upregulator Consider the text ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while << 1400W dihydrochloride >> (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and [[ iNOS ]]."". Can you identify the relation? indirect-downregulator Consider the text ""METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist (SB-207266) on the [[ cisapride ]] mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects."". Can you identify the relation? agonist Consider the text ""Subsequent analysis revealed that << cucurbitacin I >> strongly activates RhoA and the Rho effector Rho kinase ([[ ROCK ]]) in breast cancer cells and induces the formation of stress fibers."". Can you identify the relation? activator Consider the text ""The above results indicate that polyamine depletion delays the onset of apoptosis in IEC-6 cells and confers protection against DNA damaging agents, suggesting that << polyamines >> might be involved in the [[ caspase ]] activating signal cascade."". Can you identify the relation? indirect-upregulator Consider the text ""<< zRetSat A >> also saturated the 13-14 or 7-8 double bonds of [[ all-trans-3,4-didehydroretinol ]] (vitamin A2), a second endogenous form of vitamin A in zebrafish."". Can you identify the relation? substrate Consider the text ""The antagonistic property of << rilmenidine >> at [[ human alpha(2A)-adrenoceptors ]] indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved."". Can you identify the relation? antagonist Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""The procedure was to reduce liver << AOX >> activity by providing tungsten or [[ hydralazine ]] in the drinking water or to use the AOX-deficient DBA/2 mouse strain."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 229,"Question: What is the relation in the sentence ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.""? activator Question: What is the relation in the sentence ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent << amino acid >> transporter, with functional features of [[ ASCT2 ]] transport.""? upregulator Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists.""? antagonist Question: What is the relation in the sentence ""Here we found that the anticancer agent << cucurbitacin I >>, a Jak2 inhibitor, reduced the activation of [[ Rac1 ]] and motility in response to the ErbB3 ligand heregulin in breast cancer cells.""? inhibitor Question: What is the relation in the sentence ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.).""? downregulator Question: What is the relation in the sentence ""The effects of the << adenosine A3 receptor >> agonist [[ IB-MECA ]] on sodium taurocholate-induced experimental acute pancreatitis.""? agonist Question: What is the relation in the sentence ""Furthermore, compared with control groups, the plaque endothelium level of << p75(NTR) >> was 3-fold increased and the liver level of p75(NTR) was 17.4-fold increased by [[ SFO ]]-HD.""? indirect-upregulator Question: What is the relation in the sentence ""CONCLUSIONS: Total vitamin B6 is abnormally high in autism, consistent with previous reports of an impaired << pyridoxal kinase >> for the conversion of pyridoxine and pyridoxal to [[ PLP ]].""? product-of Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of [[ R-spondins ]] (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD.""? indirect-downregulator Question: What is the relation in the sentence ""Leukotriene A(4) hydrolase (<< LTA(4)H >>) is a cystolic enzyme that stereospecifically catalyzes the transformation of [[ LTA(4) ]] to LTB(4).""? substrate Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].""? agonist-activator Question: What is the relation in the sentence ""In hearts treated with << metformin >>, [AMP] was increased at 50 min and AMPK activity, phosphorylated AMPK, and [[ phosphorylated acetyl-CoA carboxylase ]] were elevated at 61 min.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 230,"Regarding the sentence ""Even though the activities of MAT and << GNMT >> were elevated, the concentration of liver S-adenosylmethionine was decreased (24%, p<0.001) and [[ S-adenosylhomocysteine ]] increased (113%, p<0.001) in the dwarf mice."", what is the relation? product-of Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Noradrenaline and << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively."", what is the relation? agonist Regarding the sentence ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", what is the relation? upregulator Regarding the sentence ""Phosphorylation of << AMPK >> at Thr172 increased by 1.4-fold within 5 min, and remained elevated throughout a 30-min time course, in response to [[ 2-deoxyglucose ]]."", what is the relation? activator Regarding the sentence ""In addition, << ethanol >> induced degradation of [[ DNA methyltransferases ]] (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", what is the relation? downregulator Regarding the sentence ""Improvements from baseline in mean << glycosylated haemoglobin >> (HbA(1c)) were significantly greater with [[ sitagliptin ]] monotherapy than with placebo in patients with type 2 diabetes."", what is the relation? indirect-upregulator Regarding the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator Regarding the sentence ""Using << paraoxon >> as a reference [[ acetylcholinesterase ]] (AChE) inhibitor, the objective of this study was to develop an adverse outcome pathway (AOP) that provided quantitative linkages across levels of biological organization during zebrafish embryogenesis."", what is the relation? inhibitor Regarding the sentence ""The inhibition of UG synthesis and << PR >> down-regulation by 5 alpha-NET and [[ 3 beta,5 alpha-NET ]] indicates that these NET metabolites possess antiprogestational properties."", what is the relation? indirect-downregulator Regarding the sentence ""alpha-Tocopherol transfer protein (<< alpha-TTP >>), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma [[ alpha-tocopherol ]] level by mediating the secretion of alpha-tocopherol by the liver."", what is the relation? substrate Regarding the sentence ""<< Betaxolol >>, a [[ beta(1)-adrenoceptor ]] antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other beta-adrenoceptor antagonists."", what is the relation? antagonist Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""<< Lintitript >> markedly increased postprandial plasma CCK release (P<0.001) while distinctly reducing postprandial [[ PP ]] levels (P<0.01) as compared to placebo."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 231,"Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor << Adenylosuccinate synthetase >> (AdSS) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP. Question: what is the relation? Answer: product-of Taken together, our study demonstrated that << SB365 >> inhibits the [[ AKT ]]/mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis. Question: what is the relation? Answer: inhibitor Pre-clinical pharmacology of zolmitriptan (<< Zomig >>; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine. Question: what is the relation? Answer: agonist << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of << Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and [[ catechol-O-methyltransferase ]] (COMT). Question: what is the relation? Answer: substrate In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: agonist-activator To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance. Question: what is the relation? Answer: upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. Question: what is the relation? Answer: antagonist Both << BRL >> and SAL produced a significant increase in postural finger tremor in keeping with [[ beta 2-adrenoceptor ]] stimulation, and this response was totally abolished by pretreatment with N20. Question: what is the relation? Answer: activator << RORalpha >> ectopic expression activated the cAspAT gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by [[ rosiglitazone ]] treatment of adipocytes. Question: what is the relation? Answer: indirect-upregulator Phospholipase A2 inhibitors p-bromophenacyl bromide and << arachidonyl trifluoromethyl ketone >> suppressed interleukin-2 ([[ IL-2 ]]) expression in murine primary splenocytes. Question: what is the relation? Answer: indirect-downregulator The in vivo inhibitory effect of << harmaline >> on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified [[ CYP2D6 ]]. Question: what is the relation? Answer: downregulator COX-1 and << COX-2 >> inhibition in horse blood by phenylbutazone, flunixin, [[ carprofen ]] and meloxicam: an in vitro analysis. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 232,"In reference to ""<< Amitriptyline >>, but not any other tricyclic or selective serotonin reuptake inhibitor antidepressants, promotes [[ TrkA ]] autophosphorylation in primary neurons and induces neurite outgrowth in PC12 cells."", what is the relation? activator In reference to ""Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing [[ NF-κB ]] activity and induction of Nrf2-dependent HO-1 activity."", what is the relation? downregulator In reference to ""Inhibition of gelatinase A (<< MMP-2 >>) by [[ batimastat ]] and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma."", what is the relation? inhibitor In reference to ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", what is the relation? agonist In reference to ""In conclusion, immortalized SHR and WKY PTE cells take up << l-alanine >> mainly through a high-affinity [[ Na(+)-dependent amino acid transporter ]], with functional features of ASCT2 transport."", what is the relation? substrate In reference to ""<< Ferredoxin 1 >> (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues."", what is the relation? product-of In reference to ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity."", what is the relation? upregulator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal NGF, [[ BDNF ]] and ChAT that was eliminated by olanzapine treatment."", what is the relation? indirect-downregulator In reference to ""<< Thiazolidinediones >> are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferator-activated receptor gamma (PPAR(gamma)) and stimulating the expression of [[ insulin ]]-responsive genes involved in glucose and lipid metabolism."", what is the relation? indirect-upregulator In reference to ""The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists SB224289 (300 microg/kg; 5-HT1B), << BRL15572 >> (300 microg/kg; [[ 5-HT1D ]]), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C)."", what is the relation? antagonist In reference to ""In this work a novel approach combining HPLC-UV on-line with oaTOF-MS and ICPMS was applied to investigate in human and rat plasma the metabolism of labelled BK (79/81 Br-Phe5) BrBK in the presence of two new dual ACE/<< NEP >> inhibitors ([[ GW660511X ]] and omapatrilat) currently under clinical trial."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 233,"Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of [[ propranolol ]]>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>atenolol."", what is the relation? antagonist Regarding the sentence ""Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal NGF, BDNF and [[ ChAT ]] that was eliminated by olanzapine treatment."", what is the relation? indirect-downregulator Regarding the sentence ""Intravenous << arginine >> significantly increased the acute [[ glucagon ]] response (129 +/- 12 vs 36 +/- 6 ng/l in controls; p < 0.01), notably without affecting plasma glucose."", what is the relation? indirect-upregulator Regarding the sentence ""The structure-activity relationships revealed that the free << hydroxyl >> group at position 5 and phosphate group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of [[ CEase ]]."", what is the relation? inhibitor Regarding the sentence ""<< Mammalian ALDH1B1 >>, another mitochondrial enzyme sharing 72% identity with ALDH2, is also capable of metabolizing [[ acetaldehyde ]] but has a tissue distribution and pattern of activity distinct from that of ALDH2."", what is the relation? substrate Regarding the sentence ""<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS)."", what is the relation? product-of Regarding the sentence ""Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats."", what is the relation? upregulator Regarding the sentence ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."", what is the relation? downregulator Regarding the sentence ""Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and [[ inositol requiring enzyme 1α ]]."", what is the relation? activator Regarding the sentence ""OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (<< AR >>) agonist ([[ dexmedetomidine ]])."", what is the relation? agonist Regarding the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""<< Imatinib >> (STI571, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-[[ ABL ]], PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 234,"Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""<< β-ionone >> was also shown to induce the expression of cleaved-[[ caspase-3 ]] and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner."", describe the relation. indirect-upregulator Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", describe the relation. agonist-activator Given the text ""<< Glyphosate >> affects aromatic amino acid biosynthesis by inhibiting 5-enolpyruvylshikimate-3-phosphate synthase ([[ EPSPS ]])."", describe the relation. inhibitor Given the text ""TAS-102 is a novel drug containing << trifluorothymidine >>, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS."", describe the relation. substrate Given the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), [[ CDK4 ]], c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", describe the relation. downregulator Given the text ""N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase (<< EC 3.1.4.45 >>; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome."", describe the relation. product-of Given the text ""In alpha2B-receptor-expressing HEK293 cells, << etomidate >> rapidly increased phosphorylation of the extracellular signal-related kinases [[ ERK1/2 ]]."", describe the relation. activator Given the text ""Saturated << palmitic and stearic acids >> increased ceramides, up-regulated [[ PTP1B ]], and had AKt and PTP1B phosphorylation at Ser 50 impaired."", describe the relation. upregulator Given the text ""METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (<< SB-207266 >>) on the cisapride mediated increase in plasma aldosterone (a [[ 5-HT(4) ]] mediated response) and orocaecal transit in 18 subjects."", describe the relation. antagonist Given the text ""The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific)."", describe the relation. agonist Given the text ""In human blood, the tested glucocorticoids beclomethasone, << dexamethasone >> and fluticasone inhibited the LPS induced [[ TNF ]] release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced TNF release, with the exception of dexamethasone, was much less pronounced."", describe the relation. indirect-downregulator Given the text ""Here, we report that << genistein >> at physiologically relevant concentrations (0.1-10 μM) significantly inhibited [[ thrombin ]]-induced increase in endothelial monolayer permeability."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 235,"Given the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited [[ p16 ]] mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control."", describe the relation. indirect-downregulator Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Low levels of << serotonin >> may reduce the density of the [[ serotonin transporter ]] (SERT) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response""."", describe the relation. downregulator Given the text ""<< Amprenavir >> efficiently activated [[ PXR ]] and induced PXR target gene expression in vitro and in vivo."", describe the relation. activator Given the text ""Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II."", describe the relation. product-of Given the text ""<< Ramelteon >> (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin [[ MT(1) ]]/MT(2) receptor agonist."", describe the relation. agonist Given the text ""Methylation-specific PCR and bisulfite sequencing identified methylation of this << CpG >> ((m)CpG) island of the glut3 gene, frequency of methylation increasing 2.5-fold with a 1.6-fold increase in [[ DNA methyl transferase 3a ]] concentrations noted with advancing postnatal age (PN14 vs PN3)."", describe the relation. indirect-upregulator Given the text ""Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors."", describe the relation. antagonist Given the text ""A structure-activity relationship (SAR) study of the << c-Myc >> (Myc) inhibitor 10074-G5 ([[ N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine ]], 1) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore."", describe the relation. inhibitor Given the text ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively."", describe the relation. upregulator Given the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", describe the relation. agonist-activator Given the text ""In the presence of the system L inhibitor BCH, Na(+)-dependent l-alanine uptake in WKY and SHR PTE cells was inhibited by alanine, serine, and cysteine, which is consistent with << amino acid >> transport through [[ ASCT2 ]]."", describe the relation. substrate Given the text ""Cyclooxygenase-1 (COX-1) inhibitors (flurbiprofen, ketoprofen and ketrolack) attenuated the nicotine-induced contraction in a concentration-dependent manner, and << cyclooxygenase-2 >> (COX-2) inhibitors at high concentrations ([[ nimesulide ]] and NS-389) slightly attenuated the contraction."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 236,"Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""HbA1c level in DM12W group was higher than in DM4W group, << HbA1c >> level in [[ EtOH ]]+DM8W group was lower than in DM8W group."", describe the relation. indirect-downregulator Given the text ""In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and [[ Bax ]] proteins."", describe the relation. indirect-upregulator Given the text ""alpha(1)-Adrenoceptor antagonists were tested against the << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach."", describe the relation. agonist Given the text ""Purified << PAOh1 >>/SMO oxidizes both spermine (K(m)=1.6 microM) and [[ N(1)-acetylspermine ]] (K(m)=51 microM), but does not oxidize spermidine."", describe the relation. substrate Given the text ""<< DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005)."", describe the relation. upregulator Given the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and [[ retinoblastoma protein ]] (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", describe the relation. downregulator Given the text ""<< Conivaptan >> is a nonpeptide dual [[ V1a/V2 AVP receptor ]] antagonist."", describe the relation. antagonist Given the text ""ATB-429-induced antinociception was reversed by << glibenclamide >>, a [[ ATP-sensitive K(+) (K(ATP)) channel ]] inhibitor."", describe the relation. inhibitor Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", describe the relation. substrate_product-of Given the text ""<< Amprenavir >> efficiently activated [[ PXR ]] and induced PXR target gene expression in vitro and in vivo."", describe the relation. activator Given the text ""CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of [[ HDC ]] gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity."", describe the relation. product-of Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""Ergot alkaloids were also effective in inhibiting << VIP >>-stimulated [[ cyclic AMP ]] production, with EC50 values for ergovaline, ergonovine, alpha-ergocryptine, ergotamine, and dopamine of 8 +/- 2, 47 +/- 2, 28 +/- 2, 2 +/- 1, and 8 +/- 1 nM, respectively."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 237,"Regarding ""Cholesterol esterase (<< CE >>) induced surface erosion of [[ poly(ethylene carbonate) ]] (PEC) and drug release from PEC under mild physiological environment was investigated."", can you determine the relation? substrate Regarding ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", can you determine the relation? substrate_product-of Regarding ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""A novel class of << quinoxalines >> has been discovered as antagonists of the IgG:[[ FcRn ]] protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen."", can you determine the relation? antagonist Regarding ""BACKGROUND: Since the introduction of the first << cholinesterase >> inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and [[ rivastigmine ]], to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase."", can you determine the relation? inhibitor Regarding ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific)."", can you determine the relation? agonist Regarding ""The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, [[ alkaline phosphatase ]], total protein, albumin, bilirubin, cholesterol, urea and creatinine)."", can you determine the relation? indirect-upregulator Regarding ""Increased immunohistochemical labeling of HIF-1alpha, VEGF, and << BNP >> in the ventricular myocardium was observed in the shunt group and [[ carvedilol ]] again normalized the labeling."", can you determine the relation? indirect-downregulator Regarding ""These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional [[ 5-HT1-like receptor ]], located to sensory nerves."", can you determine the relation? activator Regarding ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins ([[ MeCP-2 ]], MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", can you determine the relation? downregulator Regarding ""<< PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases ([[ COX ]]) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4)."", can you determine the relation? product-of Regarding ""<< DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005)."", can you determine the relation? upregulator Regarding ""Treatment with EVn-50 or << VB1 >> resulted in arresting the MDA-MB-435 and SMMC-7721 cells at G2/M phase, which was further supported by observations of increased phosphorylation of Histone 3 at Ser10, phosphorylation of [[ Cdk1 ]] at Tyr15, expression of cyclin B1, and decreased expression of Cdc25c."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 238,"Given the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", describe the relation. agonist-activator Given the text ""These results strongly suggest that << ABCA1 >> is substantially involved in hepatic [[ alpha-tocopherol ]] secretion."", describe the relation. product-of Given the text ""In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 [[ quinone ]] derivatives (AA-861, tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines."", describe the relation. activator Given the text ""<< Adenosine >> and N(6)-cyclopentyl-adenosine (CPA, [[ A1R ]] agonist) constricted MVs but not MAs."", describe the relation. agonist Given the text ""An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (<< SCH 900229 >>), a potent, PS1-selective [[ γ-secretase ]] inhibitor and clinical candidate for the treatment of Alzheimer's disease."", describe the relation. inhibitor Given the text ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent << amino acid >> transporter, with functional features of [[ ASCT2 ]] transport."", describe the relation. upregulator Given the text ""Upon co-exposure to V(5+) and TCDD, V(5+) significantly potentiated the << TCDD >>-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", describe the relation. indirect-upregulator Given the text ""Using a transient heterologous cell expression system, we find that the transport activities of the << short OATP2B1 >> variant towards substrates estrone sulfate and [[ rosuvastatin ]] are similar to the well-characterized full length variant."", describe the relation. substrate Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", describe the relation. substrate_product-of Given the text ""Low levels of << serotonin >> may reduce the density of the serotonin transporter ([[ SERT ]]) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response""."", describe the relation. downregulator Given the text ""Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors."", describe the relation. antagonist Given the text ""In conclusion, we find that << sinapic acid >> exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress [[ TGF-β1 ]] and its ability to attenuate activation of hepatic stellate cells."", describe the relation. indirect-downregulator Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""CONCLUSION: CysLT1 receptor expression in neurons is upregulated after NMDA injection, and NMDA-induced responses are inhibited by CysLT1 receptor antagonists, indicating that the increased << CysLT1 receptor >> is involved in [[ NMDA ]] excitotoxicity."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 239,"Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent [[ HO-1 ]] activity. what is the relation? downregulator Two beta(2)-agonists, formoterol and << salmeterol >>, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity. what is the relation? agonist In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport. what is the relation? upregulator Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using << dexamethasone 21-phosphate >> (DEX-P) and midazolam (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively. what is the relation? substrate In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. what is the relation? agonist-activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of By reporter gene analysis following transient transfections with various plasmids expressing a dominant negative mutant form of Cdc42, Rac1 or RhoA, << C2-ceramide >>-induced [[ SRE ]] activation was shown to be selectively repressed by pEXV-RacN17 encoding a dominant negative mutant of Rac1, suggesting that Rac activity is essential for the signalling cascade of ceramide to the nucleus. what is the relation? activator Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues. what is the relation? product-of In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor Also consistent with the involvement of Gq coupled EP1 receptors, the PGE1 stimulation is inhibited by the PKCI vector (encoding the PKC inhibitory domain), the PKC inhibitor Go 6976, thapsigargin, as well as the << calmodulin >> antagonists [[ W7 ]] and W13. what is the relation? antagonist Concentration-dependent inhibitory effects of << baicalin >> on the metabolism of dextromethorphan, a dual probe of [[ CYP2D ]] and CYP3A, in rats. what is the relation? inhibitor Synergistic cytotoxicity was demonstrated, and << pemetrexed >> significantly decreased the amount of phosphorylated Akt, enhanced apoptosis, and increased the expression of dCK in A549 and Calu-6 cells, as well as the expression of the human nucleoside equilibrative transporter 1 ([[ hENT1 ]]) in all cell lines. what is the relation? indirect-upregulator Our results have shown that << MMP-9 >> messenger ribonucleic acid (mRNA) expression was inhibited by [[ doxycycline ]] starting at 10 mg/kg/day (P<0.02). what is the relation? indirect-downregulator We show both in vitro and in vivo that low-dose << theophylline >> enhances [[ HDAC ]] activity in epithelial cells and macrophages. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 240,"Regarding ""Effects of << ORF 17583 >>, other [[ histamine H2-receptor ]] antagonists and omeprazole on gastric acid secretory states in rats and dogs."", can you determine the relation? antagonist Regarding ""On the basis of our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxification of << arylhydroxylamine >> carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R) and [[ cytochrome b5 ]] (cyt b5)."", can you determine the relation? substrate Regarding ""Here, we have now found that activation of p38 << MAPK >> by [[ anisomycin ]] potentiated induction of CYP2B6 mRNA by CAR ligand in HepG2 cells to levels observed in ligand-treated human primary hepatocytes."", can you determine the relation? indirect-upregulator Regarding ""Promoter assay revealed that << prunetin >> inhibits LPS-induced nitric oxide and prostaglandin E2 production through the suppression of [[ iNOS ]] and COX-2 at the transcriptional level."", can you determine the relation? indirect-downregulator Regarding ""This observation suggests that << MDMA >>-induced reductions in [[ SERT ]] density do not represent neuroadaptive responses to decreased levels of brain serotonin, but may occur in response to some other stimulus or to the neurotoxic effects of MDMA."", can you determine the relation? downregulator Regarding ""Systemic administration of << beta2-adrenoceptor >> agonists, formoterol and [[ salmeterol ]], elicit skeletal muscle hypertrophy in rats at micromolar doses."", can you determine the relation? agonist Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively."", can you determine the relation? upregulator Regarding ""<< DBDCT >> also caused the phosphorylation of [[ JNK ]] and p38(MAPK)."", can you determine the relation? activator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", can you determine the relation? agonist-activator Regarding ""Although inhibition of << LH >> release can be achieved by [[ estrogen ]] and progestins, an optimal inhibitory effect on the prostate is obtained by the combined administration of the antiandrogen with an LHRH agonist that causes a specific blockage of testicular androgen biosynthesis as well as an inhibition of the LH responsiveness to LHRH."", can you determine the relation? inhibitor Regarding ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system."", can you determine the relation? product-of Regarding ""<< Cabozantinib >> (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including [[ RET ]], KIT, AXL, and FLT3."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 241,"Question: What is the relation in the sentence ""<< HSYA >> suppressed the expression of TLR-4, [[ Myd88 ]], ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.""? indirect-downregulator Question: What is the relation in the sentence ""Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released << glutamate >> and its conversion to glutamine through the enzyme [[ glutamine synthetase ]] (GS).""? substrate Question: What is the relation in the sentence ""<< Indomethacin >> activates carbonic anhydrase and antagonizes the effect of the specific [[ carbonic anhydrase ]] inhibitor acetazolamide, by a direct mechanism of action.""? activator Question: What is the relation in the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity.""? agonist-activator Question: What is the relation in the sentence ""OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (<< AR >>) agonist ([[ dexmedetomidine ]]).""? agonist Question: What is the relation in the sentence ""Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity.""? upregulator Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.""? antagonist Question: What is the relation in the sentence ""Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>[[ pyridostigmine ]]=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent.""? inhibitor Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Human and rat renin and << angiotensinogen >> genes were downregulated in dTGR and were increased by [[ losartan ]] and cilazapril treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed.""? indirect-upregulator Question: What is the relation in the sentence ""BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA).""? product-of Question: What is the relation in the sentence ""Expression of the dominant negative mutants rab5A-<< N133I >> or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation.""? downregulator Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""Nicotinic-receptor potentiator drugs, huprine X and << galantamine >>, increase ACh release by blocking [[ AChE ]] activity but not acting on nicotinic receptors.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 242,"Given the text ""Inhibition of mTOR by low dose << rapamycin >> decreases HG-induced [[ Nox4 ]] and Nox1, NADPH oxidase activity and podocyte apoptosis."", describe the relation. indirect-downregulator Given the text ""These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in [[ cyclin E ]] and cdk2 kinase activities."", describe the relation. activator Given the text ""CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme."", describe the relation. upregulator Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", describe the relation. substrate_product-of Given the text ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the << EP2 >> selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", describe the relation. agonist Given the text ""A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, << ferulic acid >>, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1)."", describe the relation. inhibitor Given the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", describe the relation. agonist-activator Given the text ""The potent << histamine H(1)-receptor >> antagonist cetirizine ([[ Zyrtec ]]) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine."", describe the relation. antagonist Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""We observed a significant reduction in CSE induced luciferase expression, NF-κB DNA binding, << I-κBε >> degradation and c-Rel nuclear translocation in cells pretreated with [[ vitamin C ]]."", describe the relation. downregulator Given the text ""Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of spermidine and [[ spermine ]] with a significant accumulation of putrescine and induction of ODC."", describe the relation. product-of Given the text ""Inhibition studies revealed that the << multidrug resistance-associated proteins >> (ABCCs) are involved in the transport of [[ BPDE glutathione ]] conjugates."", describe the relation. substrate Given the text ""High << p53 >> protein levels, but not genetic or functional p53 status, were associated with increased [[ topotecan ]]-induced DNA/topoisomerase I complex formation."", describe the relation. indirect-upregulator Given the text ""Aspirin and << metformin >> (an activator of AMPK) increased inhibition of mTOR and [[ Akt ]], as well as autophagy in CRC cells."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 243,"Question: What is the relation in the sentence ""Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512).""? upregulator Question: What is the relation in the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""<< Cyclooxygenase(COX)-2 >>-derived [[ prostanoids ]] can influence several processes that are linked to carcinogenesis.""? product-of Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""<< Minocycline >> showed more potent inhibition on [[ MMP-9 ]] mRNA expression, starting at 1 (P<0.005) and further at more than 30 (P<0.001) mg/kg/day.""? indirect-downregulator Question: What is the relation in the sentence ""In the rabbit pulmonary artery, << rilmenidine >> and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan.""? antagonist Question: What is the relation in the sentence ""Synthesis, molecular modeling and evaluation of novel << N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone >> derivatives as dual inhibitors for cholinesterases and [[ Aβ ]] aggregation.""? inhibitor Question: What is the relation in the sentence ""Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective << alpha(1A)-adrenoceptor >> antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively).""? agonist Question: What is the relation in the sentence ""At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of [[ GluN1 ]]/GluN2B receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic.""? downregulator Question: What is the relation in the sentence ""Treatment of Rat-2 fibroblast cells with << C2-ceramide >> caused the stimulation of [[ c-fos SRE ]]-dependent reporter gene activity in a dose- and time-dependent manner by transient transfection analysis.""? activator Question: What is the relation in the sentence ""BACKGROUND: Histamine synthesized by << histidine decarboxylase >> (HDC) from [[ L-histidine ]] is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.""? substrate Question: What is the relation in the sentence ""<< Sphingosine-1-phosphate >> promotes the nuclear translocation of β-catenin and thereby induces [[ osteoprotegerin ]] gene expression in osteoblast-like cell lines.""? indirect-upregulator Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].""? agonist-activator Question: What is the relation in the sentence ""<< Imatinib mesylate >> is a tyrosine kinase inhibitor of the [[ ABL ]], platelet-derived growth factor receptor (PDGFR), and c-kit kinases.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 244,"<< Indomethacin >> activates carbonic anhydrase and antagonizes the effect of the specific [[ carbonic anhydrase ]] inhibitor acetazolamide, by a direct mechanism of action. Query: What is the relation? activator Terfenadine and astemizole are chemically unrelated to << histamine H1-receptor >> antagonists such as diphenhydramine and [[ chlorpheniramine ]]. Query: What is the relation? antagonist Prolonged use of << tolvaptan >> leads to increased endogenous levels of [[ AVP ]] and perhaps over-stimulation of V(1A) receptors. Query: What is the relation? indirect-upregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Query: What is the relation? substrate_product-of Furthermore, proteosomal inhibitor << MG132 >> suppressed [[ AMPK ]] activation, GSK3β phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells. Query: What is the relation? inhibitor In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), [[ interleukin-6 ]] (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells. Query: What is the relation? indirect-downregulator Compound 6 stimulated << OATP1B3 >>-mediated [[ estradiol 17β-glucuronide ]] uptake by increasing the apparent affinity of OATP1B3 for its substrate. Query: What is the relation? substrate The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific). Query: What is the relation? agonist These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. Query: What is the relation? upregulator << U50, 488H >> caused a significant down-regulation of the [[ hkor ]], although etorphine did not. Query: What is the relation? downregulator On the other hand, the accumulation of << Ser >> through the C1-THF synthase/[[ SHMT ]] pathway in glyD plants was 2.5-fold greater than that in WT plants. Query: What is the relation? product-of Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor Radioligand binding studies with the nonselective << alpha 1-adrenoceptor >> antagonist radioligand [[ 125I-BE2254 ]] showed that 73-87% of the binding sites in rabbit aorta are CEC sensitive and they are predominantly low affinity sites both for WB4101 (pKd = 8.1) and for 5-methylurapidil (pKd = 7.1). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 245,"Regarding the sentence ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."", what is the relation? downregulator Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, [[ OSI-774 ]]), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux)."", what is the relation? inhibitor Regarding the sentence ""Amrinone and << milrinone >>, selective PDE3 inhibitors, suppressed [[ TNF ]] secretion to a lesser extent."", what is the relation? indirect-downregulator Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""4-Hydroxynonenal (4-HNE) is a mutagenic << alpha,beta-unsaturated aldehyde >> produced during oxidative injury that is conjugated by several [[ glutathione S-transferase ]] (GST) isoforms."", what is the relation? substrate Regarding the sentence ""In the present study, we identified << amprenavir >>, a widely used HIV PI, as a potent [[ PXR ]]-selective agonist."", what is the relation? agonist Regarding the sentence ""We have shown that << COX-2 >> mediates acid-induced [[ PGE2 ]] production."", what is the relation? product-of Regarding the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator Regarding the sentence ""An amphiphile with branched << poly(ethylene glycol) >> architecture also activated the [[ lectin ]] pathway but only through L-ficolin recognition."", what is the relation? activator Regarding the sentence ""<< (+/-)-Tamsulosin >> effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of [[ alpha 1B-adrenoceptors ]] by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine."", what is the relation? antagonist Regarding the sentence ""<< Phenobarbital >> (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including erythropoietin, heme oxygenase-1 and [[ vascular endothelial growth factor-a ]]."", what is the relation? indirect-upregulator Regarding the sentence ""The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of [[ AchE ]] activity, CRP, NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level."", what is the relation? upregulator Regarding the sentence ""A 5'-flanking region capable of supporting << RA >>-induced [[ blr1 ]] activation in HL-60 cells was found to contain a 205-bp sequence in the distal portion that was necessary for transcriptional activation by RA."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 246,"Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist [[ formoterol ]] [eformoterol]. Question: what is the relation? Answer: agonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor Human and rat renin and << angiotensinogen >> genes were downregulated in dTGR and were increased by losartan and [[ cilazapril ]] treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed. Question: what is the relation? Answer: indirect-upregulator << Thalidomide >> inhibits growth of tumors through [[ COX-2 ]] degradation independent of antiangiogenesis. Question: what is the relation? Answer: inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of The starting point for the calculations is the recent X-ray crystal structure of << GNMT >> complexed with [[ SAM ]] and acetate. Question: what is the relation? Answer: substrate RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Question: what is the relation? Answer: agonist-activator << All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]]. Question: what is the relation? Answer: upregulator The potentiation of the contractile effect induced by 5-HT is only somewhat modified by deendothelialization, but abolished by the << thromboxane A2 receptor >> antagonists GR32191 and [[ ridogrel ]]. Question: what is the relation? Answer: antagonist In the << IB-MECA >> group, [[ α-amylase ]] activity was decreased with statistically high significance compared to group I. Question: what is the relation? Answer: indirect-downregulator These results suggest that << ACS1 >> and ACS4 may be linked to [[ triacylglycerol ]] synthesis. Question: what is the relation? Answer: product-of Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]]. Question: what is the relation? Answer: downregulator Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of << caspase 3 >> and release of cytochrome c to the cytosol induced by [[ DZN ]]. Question: what is the relation? Answer: activator We have previously demonstrated that phosphorylation of Fas-associated death domain-containing protein (<< FADD >>) at 194 serine through c-jun NH2-terminal kinase (JNK) activation sensitizes breast cancer cells to chemotherapy through accelerating cell cycle arrest at G2/M, and that Bcl-2 phosphorylation downstream of JNK/FADD plays an important role in cell growth suppression by [[ paclitaxel ]]. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 247,"Risperidone is metabolized to its active metabolite, << 9-hydroxyrisperidone >>, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4. Please explain the relation. product-of One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of << Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of [[ caspase 3 ]] and release of cytochrome c to the cytosol induced by DZN. Please explain the relation. indirect-upregulator Low levels of << serotonin >> may reduce the density of the serotonin transporter ([[ SERT ]]) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response"". Please explain the relation. downregulator The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the << beta-adrenoceptor >> blocker with high affinity for 5-HT1A and 5-HT1B binding sites [[ (+/-)-pindolol ]] (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM). Please explain the relation. inhibitor << Dexamethasone >> (DXM) decreased the expression of [[ CXCL-8 ]], VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS. Please explain the relation. indirect-downregulator Subsequent analysis revealed that << cucurbitacin I >> strongly activates RhoA and the Rho effector Rho kinase ([[ ROCK ]]) in breast cancer cells and induces the formation of stress fibers. Please explain the relation. activator Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner. Please explain the relation. upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Please explain the relation. agonist-activator These findings demonstrate that << PEPT2 >> is the primary transporter responsible for [[ cefadroxil ]] uptake in the choroid plexus. Please explain the relation. substrate The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure. Please explain the relation. agonist The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals. Please explain the relation. antagonist Moreover, << geldanamycin >> decreases the amount and phosphorylation of Lck and Raf-1 kinases and prevents activation of the [[ extracellular signal regulated kinase (ERK)-2 ]] kinase. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 248,"The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Query: What is the relation? agonist << Cycloxygenase-2 >> (COX-2)-derived [[ prostaglandin E2 ]] (PGE2) has been shown to be important in esophageal tumorigenesis. Query: What is the relation? product-of Further, << 5HHMF >> increased specific DNA-binding activity of [[ Nrf2 ]], and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity. Query: What is the relation? activator In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent << amino acid >> transporter, with functional features of [[ ASCT2 ]] transport. Query: What is the relation? upregulator Alprenolol and << bromoacetylalprenololmenthane >> are competitive slowly reversible antagonists at the [[ beta 1-adrenoceptors ]] of rat left atria. Query: What is the relation? antagonist Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of << Allicin >> treatment showed reduced production of pro-inflammatory [[ cytokines ]] and NO and increased HO-1 activity. Query: What is the relation? indirect-downregulator METHODS: << COX-1 >> inhibition was determined by measuring thromboxane B2 (TXB2)-generation from clotting whole blood ex vivo after single oral doses of 7.5 and 15 mg meloxicam and 75 mg diclofenac and at steady state (15 mg [[ meloxicam ]] daily and 150 mg diclofenac daily). Query: What is the relation? inhibitor << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator On the other hand, treatment with << gentianine >> significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-γ, [[ GLUT-4 ]] and adiponectin. Query: What is the relation? indirect-upregulator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, [[ cyclin dependent kinase 2 ]] (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Query: What is the relation? downregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor Dopamine D(2) receptor-induced << COX-2 >>-mediated production of [[ prostaglandin E(2) ]] in D(2)-transfected Chinese hamster ovary cells without simultaneous administration of a Ca(2+)-mobilizing agent. Query: What is the relation? substrate Through immunoblotting analysis, it was found that << AdOx >> was capable of indirectly diminishing the phosphorylation of oncogenic Src and its [[ kinase ]] activity. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 249,"In reference to ""The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific)."", what is the relation? agonist In reference to ""(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, << SNAP 1069 >> and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]."", what is the relation? antagonist In reference to ""6-DHSG was metabolised by GSH to form a GSH conjugate (<< GS-6-DHSG >>) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of glutathione-S-transferase ([[ GST ]])."", what is the relation? product-of In reference to ""Transport by OATP1B1 and << OATP1B3 >> enhances the cytotoxicity of [[ epigallocatechin 3-O-gallate ]] and several quercetin derivatives."", what is the relation? substrate In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, [[ Bak ]], cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27."", what is the relation? indirect-upregulator In reference to ""In alpha2B-receptor-expressing HEK293 cells, << etomidate >> rapidly increased phosphorylation of the extracellular signal-related kinases [[ ERK1/2 ]]."", what is the relation? activator In reference to ""Increased phosphorylation of p95ErbB2 and << AKT >> in response to HRG was abrogated to varying degrees by [[ GW572016 ]]."", what is the relation? inhibitor In reference to ""Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner."", what is the relation? upregulator In reference to ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", what is the relation? agonist-activator In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, [[ nuclear factor-kappaB ]] and activating protein-1, which were increased in fructose-fed rats."", what is the relation? downregulator In reference to ""<< HSYA >> suppressed the expression of TLR-4, [[ Myd88 ]], ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells."", what is the relation? indirect-downregulator In reference to ""The quinolizidine alkaloids (natural products) such as oxymatrine, << sophoridine >>, sophocarpine and matrine carry the common molecular structure of O=C=N-C-C-C-N that possessed positive ionotropic effect and [[ hERG ]] blocking activity."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 250,"Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as GluN1/GluN2B [[ N-Methyl-D-aspartate Receptor ]] Antagonists. Query: What is the relation? antagonist These results indicate that phillyrin prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that << phillyrin >> is a novel [[ AMPK ]] activator with a role in the prevention and treatment of obesity. Query: What is the relation? activator In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Query: What is the relation? agonist-activator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Brexpiprazole reversed the inhibitory effect of the DA agonist << apomorphine >> on VTA DA neurons (ED50 = 61 mug/kg), whereas it was ineffective when administered alone, indicating partial agonistic action on [[ D2 receptors ]]. Query: What is the relation? agonist Moreover, LTD4-induced increases in CysLT(1)R and << NF-κB >> p65 in the brain were also attenuated by [[ pranlukast ]]. Query: What is the relation? indirect-downregulator Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration. Query: What is the relation? upregulator In addition, << tolvaptan >> is metabolized by the [[ CYP3A4 ]] system; thus physicians should be aware of the potential for increased interactions with other medications. Query: What is the relation? substrate Lung inflammation, << IL-4 >> production, and airway mast cell activity were also prevented under this early short-term treatment with [[ PGE2 ]]. Query: What is the relation? inhibitor The in vivo inhibitory effect of << harmaline >> on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified [[ CYP2D6 ]]. Query: What is the relation? downregulator Interestingly, the allele of PRO1 was shown to enhance the activities of gamma-glutamyl kinase and << gamma-glutamyl phosphate reductase >>, both of which catalyze the first two steps of [[ L-proline ]] synthesis from L-glutamate and which together may form a complex in vivo. Query: What is the relation? product-of Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Thiazolidinediones >> are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferator-activated receptor gamma (PPAR(gamma)) and stimulating the expression of [[ insulin ]]-responsive genes involved in glucose and lipid metabolism. Query: What is the relation? indirect-upregulator Metabolism of << triethylenetetramine >> and 1,12-diamino-3,6,9-triazadodecane by the [[ spermidine/spermine-N(1)-acetyltransferase ]] and thialysine acetyltransferase. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 251,"These studies suggest that HER2-overexpressing tumors are particularly susceptible to the inhibition of HER family << tyrosine kinase >>[[ tyrosine ]] kinase signaling and suggest novel strategies to treat these particularly aggressive tumors. Please explain the relation. substrate Pharmacological properties of << lorglumide >> as a member of a new class of [[ cholecystokinin ]] antagonists. Please explain the relation. antagonist Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of [[ human carboxylesterases 1 ]] (hCES1) and 2 (hCES2). Please explain the relation. inhibitor These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by [[ SP ]]-NK-1R related pathway in mouse pancreatic acinar cells. Please explain the relation. product-of << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by << TCDD >>, siRNA-mediated [[ Cx43 ]] knock-down was not sufficient to stimulate proliferation in contact-inhibited cells. Please explain the relation. downregulator Terbutaline (Bricanyl) and its prodrug << Bambuterol >> (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients. Please explain the relation. agonist << Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase ([[ ERK ]]) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway. Please explain the relation. indirect-downregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Please explain the relation. upregulator In this study, using reverse transcriptase PCR (RT-PCR) and ELISA, we showed that << TCDD >> up-regulated the expression and secretion of tumor necrosis factor-alpha ([[ TNF-α ]]) in a time-dependent manner in cultured HAPI microglial cells. Please explain the relation. indirect-upregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator Extracellular application of << meclofenamate >> (EC(50) = 25 microM) and diclofenac (EC(50) = 2.6 microM) resulted in the activation of [[ KCNQ2/Q3 ]] K(+) currents, heterologously expressed in Chinese hamster ovary cells. Please explain the relation. activator Results showed that DMF increased nuclear levels of Nrf2, and both << DMF >> and adenovirus-mediated overexpression of Nrf2 (Ad-Nrf2) decreased PAI-1, alpha-smooth muscle actin (alpha-SMA), fibronectin and [[ type 1 collagen ]] expression in TGF-beta-treated rat mesangial cells (RMCs) and renal fibroblast cells (NRK-49F). Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 252,"Regarding ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", can you determine the relation? substrate_product-of Regarding ""The non-selective << adenosine receptor >> antagonist ([[ caffeine ]]), and the selective adenosine A1 receptor antagonist (DPCPX), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice."", can you determine the relation? antagonist Regarding ""Activation of AMP-activated Protein Kinase and Phosphorylation of << Glycogen Synthase Kinase3 β >> Mediate [[ Ursolic Acid ]] Induced Apoptosis in HepG2 Liver Cancer Cells."", can you determine the relation? activator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", can you determine the relation? agonist-activator Regarding ""The latter reaction, catalyzed by aspartoacylase (<< ASPA >>), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter."", can you determine the relation? product-of Regarding ""<< Mouse brain serine racemase >> catalyzes specific elimination of [[ L-serine ]] to pyruvate."", can you determine the relation? substrate Regarding ""2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", can you determine the relation? agonist Regarding ""Meanwhile, the serum level of KC (a functional homolog of << IL-8 >> and the main proinflammatory alpha chemokine in mice) in apoE(-/-) mice was up to 357pg/ml in [[ SFO ]]-HD treated group."", can you determine the relation? indirect-upregulator Regarding ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively."", can you determine the relation? upregulator Regarding ""This study explored whether << curcumin >> improves colonic inflammation in a rat colitis model through inhibition of the TLR4/NF-κB signaling pathway and [[ IL-27 ]] expression."", can you determine the relation? indirect-downregulator Regarding ""5-(N,N-dimethyl)-amiloride (50 microM; << DMA >>), a concentration that selectively inhibits the NHE isoforms [[ NHE1 ]] and NHE2, but not NHE3, did not affect DBS."", can you determine the relation? inhibitor Regarding ""In combination with clofarabine, the ability of << resveratrol >> to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment."", can you determine the relation? downregulator Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""Targeted disruption of the gene encoding the N-glycosyltransferase, prlH, abolished pyralomicin production, and recombinant expression of PrlA confirms the activity of this enzyme as a << sugar phosphate cyclase >> involved in the formation of the C7-[[ cyclitol ]] moiety."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 253,"Question: What is the relation in the sentence ""We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the << chenodeoxycholic acid >> (CDCA)-induced expression of Cdx2 and [[ MUC2 ]] in normal rat gastric epithelial cells (RGM-1 cells).""? indirect-upregulator Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]].""? agonist-activator Question: What is the relation in the sentence ""Since << gemfibrozil >> is known to activate [[ peroxisome proliferator-activated receptor-alpha ]] (PPAR-alpha), we investigated the role of PPAR-alpha in gemfibrozil-mediated inhibition of iNOS.""? activator Question: What is the relation in the sentence ""Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of [[ DA ]] prevented the MDMA-induced reduction in plasmalemmal DA transport.""? substrate Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""A << naloxone-steroid hybrid azine >> with selective and long-acting opioid antagonism at [[ delta receptors ]] in vitro.""? antagonist Question: What is the relation in the sentence ""<< Mibefradil >> blocked currents of all [[ Na+ channel ]] isoforms with similar affinity and a dependence on holding potential, and drug off-rate was slowed at depolarized potentials (k(off) was 0.024/s at -130 mV and 0.007/s at -100 mV for Nav1.5).""? inhibitor Question: What is the relation in the sentence ""In contrast, there was little change in mRNA levels for GTP cyclohydrolase I (<< GTPCH >>), the rate limiting enzyme in synthesis of the tetrahydrobiopterin ([[ BH4 ]]), the obligate cofactor for TPH.""? product-of Question: What is the relation in the sentence ""<< Rofecoxib >> only diminished COX-2 protein expression and [[ MCP-1 ]] gene expression in vascular atheroma.""? indirect-downregulator Question: What is the relation in the sentence ""The in vivo inhibitory effect of << harmaline >> on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified [[ CYP2D6 ]].""? downregulator Question: What is the relation in the sentence ""Zolmitriptan (<< Zomig >>; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura.""? agonist Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.).""? upregulator Question: What is the relation in the sentence ""We studied in a clinical trial whether isolated isoflavone treatment in postmenopausal women could affect reverse cholesterol transport as evaluated by adenosine triphosphate-binding cassette A1- (<< ABCA1 >>), dependent [[ cholesterol ]] efflux from macrophages.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 254,"Given the text ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific)."", describe the relation. agonist Given the text ""This surprising correlation between the lack of OTC expression and sensitivity of ASS-positive HCC cells shows that OTC-deficient HCCs are sensitive to << rhArg >>-mediated [[ arginine ]] depletion."", describe the relation. substrate Given the text ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", describe the relation. downregulator Given the text ""<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS)."", describe the relation. product-of Given the text ""Differences in magnitude of Na(+)-dependent << l-alanine >> uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", describe the relation. upregulator Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""<< Tolbutamide >> and gliclazide block the K(ATP) channel [[ K(ir)6.2 ]]/Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells."", describe the relation. inhibitor Given the text ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and [[ BT-03 ]] possessing asymmetric structure."", describe the relation. activator Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", describe the relation. substrate_product-of Given the text ""In addition to << CYP2B6 >>, [[ anisomycin ]] co-treatment potentiated an increase in CYP2A7 and CYP2C9 mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs."", describe the relation. indirect-upregulator Given the text ""Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, << ketanserin >> (10 microM), a [[ 5-HT2 ]] antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect."", describe the relation. antagonist Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), [[ lactic dehydrogenase ]] (LDH), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system."", describe the relation. indirect-downregulator Given the text ""FMLP/CB-stimulated translocation of << cPLA2 >> to the nuclear envelope assessed by specific immunohistochemical staining also was blocked by [[ FP ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 255,"<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system. Question: what is the relation? Answer: product-of In the present study, we compared the pharmacology of (+/-)pindolol, << WAY-100635 >> (a [[ 5-HT(1A) ]] antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. Question: what is the relation? Answer: antagonist In general, rifampicin can act on a pattern: << rifampicin >> activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: activator Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of sildenafil (<< Viagra >>, Pfizer) - the first approved selective [[ PDE ]] inhibitor for the treatment of ED. Question: what is the relation? Answer: inhibitor Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. Question: what is the relation? Answer: upregulator Furthermore, N-<< BPs >> decreased the levels of [[ phosphorylated extracellular signal-regulated kinase ]] (ERK) and mTOR via suppression of Ras prenylation and enhanced Bim expression. Question: what is the relation? Answer: indirect-downregulator Coexpression of GRK2 or GRK2 and arrestin-2 permitted << etorphine >> to induce down-regulation of the [[ hkor ]], although expression of arrestin-2 or dynamin I alone did not. Question: what is the relation? Answer: downregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure. Question: what is the relation? Answer: agonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Question: what is the relation? Answer: substrate_product-of In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(V)1.5 << sodium channels >>[[ sodium ]] channels expressed in Chinese Hamster Ovary (CHO-K1) cells. Question: what is the relation? Answer: substrate << S1P >> activated phosphatidylinositol 3-kinase ([[ PI3K ]])/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells. Question: what is the relation? Answer: indirect-upregulator We examined the effects of the high dose of granulocyte-colony stimulating factor (G-CSF), which is capable of increasing peripheral neutrophils, and a specific << neutrophil elastase >> inhibitor ([[ ONO-5046 ]]) on acid lung injury in rats. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 256,"The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Please explain the relation. agonist-activator The antipsychotic drugs sertindole and << pimozide >> block [[ erg3 ]], a human brain K(+) channel. Please explain the relation. inhibitor To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance. Please explain the relation. upregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of CONCLUSIONS A diet that partially replaces << carbohydrate >> with unsaturated fat may improve [[ insulin ]] sensitivity in a population at risk for cardiovascular disease. Please explain the relation. indirect-upregulator Coexpression of GRK2 or GRK2 and arrestin-2 permitted << etorphine >> to induce down-regulation of the [[ hkor ]], although expression of arrestin-2 or dynamin I alone did not. Please explain the relation. downregulator EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists [[ ONO-AE3-208 ]] and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth. Please explain the relation. antagonist Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that << artemisinic acid >> regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the hydroxymethylglutaryl CoA (HMG CoA) reductase gene, which was mediated through reduced expression of the [[ CCAAT/enhancer-binding protein (C/EBP) α ]] gene. Please explain the relation. indirect-downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and << cytochrome P450 >>, compared to the [[ CCl4 ]] only group. Please explain the relation. activator They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of arginine with rhArg, to citrulline, which is converted back to << arginine >> via [[ ASS ]]. Please explain the relation. substrate Our results suggest that arsenite can potentiate EDHF-type relaxations via a mechanism that is dependent on hydrogen peroxide, thus demonstrating that dismutation of the << superoxide >> anion generated by [[ NADPH oxidase ]] can potentially offset loss of NO bioavailability under conditions of reduced eNOS activity. Please explain the relation. product-of To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective << 5-HT1F >> receptor agonist ([[ LY 344864 ]]) on c-fos protein expression in the trigeminal nucleus caudalis. Please explain the relation. agonist The << caspase-3 >> immunopositivity was increased in degenerating neurons of the [[ Cd ]] group. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 257,"Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full << muscarinic receptor >> agonist [[ methacholine ]], the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine."", describe the relation. agonist Given the text ""Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory [[ cytokines ]], increased adiponectin expression and improved glucose tolerance parallel to insulin sensitivity in obese mice."", describe the relation. indirect-downregulator Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""Evidence has accumulated in the last few years that the expression of the << microsomal/peroxidase antigen >> (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis."", describe the relation. upregulator Given the text ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of VEGFand [[ MMP-9 ]], resulting from the inhibition of Akt pathway."", describe the relation. downregulator Given the text ""<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB ([[ NF-κB ]]), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2)."", describe the relation. activator Given the text ""RESULTS: Fractionated bulb extracts and the two isolated << steroidal glycoalkaloids >> (1) and (2) induced NO production and [[ TGF-β receptor I ]] mRNA expression in fibroblast cell culture."", describe the relation. indirect-upregulator Given the text ""These protective effects were abolished by glucocorticoid receptor (<< GR >>) antagonist [[ RU486 ]] or p-ERK inhibitor U0126 rather than estrogen receptor α antagonist ICI 82,780."", describe the relation. antagonist Given the text ""<< Epidermal growth factor receptor >> inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, [[ OSI-774 ]]), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux)."", describe the relation. inhibitor Given the text ""These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by SP-[[ NK-1R ]] related pathway in mouse pancreatic acinar cells."", describe the relation. product-of Given the text ""Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both << cAMP >> and cGMP ([[ PDE10A ]])."", describe the relation. substrate Given the text ""These observations show substrate- and enzyme-specific << PTP >> inhibition by [[ alendronate ]] and support the possibility that a certain PTP(s) may be the molecular target for alendronate action."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 258,"The treatment of U937 cells with << NRF2 >> inducers including [[ sulforaphane ]] effectively elevated the expression of AKR1B1, 1B10, 1C1, 1C2, and 1C3. what is the relation? activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Apple << polyphenols >> suppress antigen presentation of [[ ovalbumin ]] by THP-1-derived dendritic cells. what is the relation? downregulator Here we report that << captopril >> treatment resulted in decreased transcription and protein levels of [[ gelatinase A ]] by 3LL cells. what is the relation? indirect-downregulator CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. what is the relation? upregulator The << mitochondrial respiratory chain complex IV >> (cytochrome c oxidase) is a multi-subunit enzyme that transfers electrons from cytochrome c to molecular [[ oxygen ]], yielding water. what is the relation? substrate One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and << 5-HT4 >> receptor antagonist ICS205930 ([[ tropisetron ]]; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM). what is the relation? antagonist In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and [[ Bax ]] proteins. what is the relation? indirect-upregulator These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves. what is the relation? agonist First, addition of apolipoprotein A-I (<< apoA-I >>), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner. what is the relation? product-of The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (<< RNase A >>) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and [[ 2'-cytidine monophosphate ]] (2'CMP) inhibitor binding. what is the relation? inhibitor The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. what is the relation? agonist-activator In the high-dose << ROAc >> group, there was a twofold increase in [[ prothrombin ]] times but only after prolonged dosing. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 259,"Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Question: what is the relation? Answer: agonist-activator For AII and << ET1 >>, MAP was also increased for the [[ fenofibrate ]] group but not in a dose-dependent fashion. Question: what is the relation? Answer: indirect-upregulator This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of << TCDD >> on canonical [[ Wnt ]] signaling and prostatic bud formation. Question: what is the relation? Answer: indirect-downregulator RESULTS: Ketorolac was six times more active against << COX-1 >> (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while [[ bromfenac ]] was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM). Question: what is the relation? Answer: downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor Further, 5HHMF increased specific DNA-binding activity of << Nrf2 >>, and transient knockdown with Nrf2 siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. Question: what is the relation? Answer: upregulator Also, << vinblastine >> enhances the phosphorylation of [[ Ras homologous protein A ]], the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α. Question: what is the relation? Answer: activator OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting << alpha2 adrenergic receptor >> (AR) agonist ([[ dexmedetomidine ]]). Question: what is the relation? Answer: agonist The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and << AH 6809 >> (EP1 and [[ EP2 ]] specific). Question: what is the relation? Answer: antagonist Compound 6 stimulated << OATP1B3 >>-mediated [[ estradiol 17β-glucuronide ]] uptake by increasing the apparent affinity of OATP1B3 for its substrate. Question: what is the relation? Answer: substrate METHODS: << Cyclooxygenase >> activity and selectivity was determined in vitro by measuring prostaglandin E(2) ([[ PGE(2) ]]) production following incubation of varying concentrations of NSAID with human recombinant COX-1 or COX-2 and arachidonic acid. Question: what is the relation? Answer: product-of We also observed that << fisetin >> efficiently suppressed the phosphorylation of [[ Akt ]], S6K1 and mTORC1 in adipose tissue. Question: what is the relation? Answer: inhibitor Therefore, decreases of PLK and << PNPO >> in the hippocampal CA1 region of aged brains may be involved in aging processes related with gamma-aminobutyric acid ([[ GABA ]]) function. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 260,"Consider the text ""METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of << [(3)H] dopamine >> (DA) uptake and [(3)H]WIN 35428 binding in human dopamine transporter ([[ DAT ]]) wild-type and mutants with altered conformational equilibria."". Can you identify the relation? substrate Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers << DEX >> blocked IL-2 production and decreased [[ IL-2R alpha ]] expression and proliferation; 2) In high IL-2 producers DEX inhibited IL-2 production partially and enhanced IL-2R alpha expression and proliferation."". Can you identify the relation? indirect-downregulator Consider the text ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."". Can you identify the relation? downregulator Consider the text ""The << BH(4) >> treatment was associated with a 2-fold increase in [[ eNOS ]] activity as well as a 70% reduction in endothelial O(2)(-) production compared with those in fructose-fed rats."". Can you identify the relation? activator Consider the text ""Block of << human NaV1.5 >> sodium channels by novel alpha-hydroxyphenylamide analogues of [[ phenytoin ]]."". Can you identify the relation? inhibitor Consider the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""The potency of the selective alpha 1D-adrenoceptor antagonist BMY 7378 against noradrenaline (pA2 = 6.16 +/- 0.13) and of the selective << alpha 1A-adrenoceptor >> antagonist [[ RS-17053 ]] against noradrenaline (pKB = 8.35 +/- 0.10) and against the selective alpha 1A-adrenoceptor agonist A-61603 (pKB = 8.40 +/- 0.09) were too low to account for alpha 1D- and alpha 1A-adrenoceptor involvement."". Can you identify the relation? antagonist Consider the text ""The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure."". Can you identify the relation? agonist Consider the text ""<< Epi >> increased both [[ WNT6 ]]/Wnt6 and Cav1 expression in human GC cells and within the tumor area of a murine model of GC (CEA424-SV40 TAg)."". Can you identify the relation? indirect-upregulator Consider the text ""Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats."". Can you identify the relation? upregulator Consider the text ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues."". Can you identify the relation? product-of Consider the text ""Using the << alpha 1-adrenoceptor >> subtype-selective antagonists chlorethylclonidine (CEC), [[ WB4101 ]], and 5-methyl-urapidil, we have examined the possible heterogeneity in the alpha 1-adrenoceptor populations in rabbit aorta."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 261,"It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of [[ I-κBε ]] and nuclear translocation of c-Rel/p50 in alveolar epithelial cells. Query: What is the relation? downregulator Our results indicate that Salix extract 1520L inhibits << COX-2 >>-mediated [[ PGE2 ]] release through compounds other than salicin or salicylate. Query: What is the relation? product-of The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound [[ BT-07-4M ]], TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. Query: What is the relation? activator In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with [[ rauwolscine ]], phentolamine, and idazoxan. Query: What is the relation? antagonist The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]]. Query: What is the relation? indirect-downregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor Choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (<< BHMT >>) are 2 enzymes involved in [[ choline ]] oxidation. Query: What is the relation? substrate While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of [[ H1-receptor ]] antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity. Query: What is the relation? agonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Query: What is the relation? substrate_product-of << Cobalt chloride >>, a typical HIF activator, induced the gene expression of CAR-target genes, including [[ cyp2b9 ]] and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver. Query: What is the relation? indirect-upregulator Sitagliptin. << Sitagliptin >>, an oral [[ dipeptidyl peptidase-4 ]] (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Query: What is the relation? inhibitor db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively. Query: What is the relation? upregulator Non-<< steroidal >> anti-inflammatory drugs (NSAIDs) are competitive inhibitors of [[ cyclooxygenase ]] (COX), the enzyme that mediates biosynthesis of prostaglandins and thromboxanes from arachidonic acid. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 262,"Given the text ""Both 5 alpha-NET and << 3 beta,5 alpha-NET >> blocked the [[ PR ]] down-regulation induced by P4 as assessed by Western and Northern blot methods."", describe the relation. indirect-upregulator Given the text ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of << L-alanine >> for [[ aminopeptidase N ]], 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B."", describe the relation. substrate Given the text ""Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats."", describe the relation. upregulator Given the text ""<< 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate >> and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual aromatase and [[ sulfatase ]] inhibitors (DASIs)."", describe the relation. inhibitor Given the text ""<< Indomethacin >> completely antagonizes CA activity, i.e. abolishes the inhibitory effect of acetazolamide on [[ CA ]]."", describe the relation. activator Given the text ""The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, [[ glutamate synthase ]], and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings."", describe the relation. downregulator Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the << alpha 1-adrenoceptor >> antagonist [[ prazosin ]] (0.01-1 microM)."", describe the relation. antagonist Given the text ""<< Agmatine >>, locally synthesized, is an endogenous agonist at [[ imidazoline receptors ]], a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter."", describe the relation. agonist Given the text ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system."", describe the relation. product-of Given the text ""Similar to gemfibrozil, clofibrate, another << fibrate >> drug, also inhibited the expression of [[ iNOS ]]."", describe the relation. indirect-downregulator Given the text ""The MCAO-induced decrease in insulin receptor levels in the liver and skeletal muscle on day 1 was recovered to control levels by orexin-A, and this effect of << orexin-A >> was reversed by the administration of [[ SB334867 ]] as well as by hypothalamic BDNF knockdown."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 263,"This study assessed changes in myocardial ALDH2 expression in the diabetic rat, in particular the diabetic rat pretreated with << ALDH2 >> activator ethanol ([[ EtOH ]]). Query: What is the relation? activator Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor << manumycin A >> caused elevation of [[ ApoA-I ]] secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. Query: What is the relation? indirect-upregulator The in vivo inhibitory effect of << harmaline >> on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified [[ CYP2D6 ]]. Query: What is the relation? downregulator Effect of << (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide >> (ramelteon, TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice. Query: What is the relation? agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Query: What is the relation? substrate_product-of The concomitantly administered effects of << rifampicin >> on other drugs can result in their altered metabolism or transportation that are metabolised by [[ cytochromes P450 ]] or transported by p-glycoprotein in the gastrointestinal tract and liver. Query: What is the relation? substrate A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and << ellagic acid >>, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase ([[ CA ]], EC 4.2.1.1). Query: What is the relation? inhibitor Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while << 1400W dihydrochloride >> (1400W), a selective inhibitor of iNOS, decreased the expression of [[ E-selectin ]], VEGF, and iNOS. Query: What is the relation? indirect-downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor G6PC2: A Negative Regulator of Basal << Glucose >>-Stimulated [[ Insulin ]] Secretion. Query: What is the relation? upregulator The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals. Query: What is the relation? antagonist Prednisolone also inhibited ACTH and << cortisol >> secretion in response to exogenous [[ CRH ]] stimulation, inferring rapid feedback inhibition at the anterior pituitary. Query: What is the relation? product-of In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Query: What is the relation? agonist-activator These findings demonstrate that << n-3 and n-6 PUFA >> increased [[ PPARgamma ]] activity is necessary for the COX-2 induction in HaCaT human keratinocyte cells. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 264,"Regarding ""Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, [[ nuclear factor-kappaB ]] and activating protein-1, which were increased in fructose-fed rats."", can you determine the relation? downregulator Regarding ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", can you determine the relation? agonist-activator Regarding ""<< EP(1) >> and EP(3) receptor antagonists [[ ONO-8713 ]] and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."", can you determine the relation? antagonist Regarding ""We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (<< PhIP >>; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]."", can you determine the relation? substrate Regarding ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of << cytochrome c >> to the cytosol induced by [[ DZN ]]."", can you determine the relation? indirect-upregulator Regarding ""<< 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to [[ TSC2 ]]."", can you determine the relation? activator Regarding ""Spiro heterocycles as potential inhibitors of << SIRT1 >>: Pd/C-mediated synthesis of novel [[ N-indolylmethyl spiroindoline-3,2'-quinazolines ]]."", can you determine the relation? inhibitor Regarding ""While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early [[ H1-receptor ]] antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity."", can you determine the relation? agonist Regarding ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]]."", can you determine the relation? upregulator Regarding ""In contrast to adrenaline and << somatostatin >>, galanin, another inhibitor of [[ insulin ]] secretion, reduced Ca2+ currents by about 40% in a pertussis toxin-insensitive manner."", can you determine the relation? indirect-downregulator Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (<< 5-FU >>) by thymidine phosphorylase ([[ TP ]]) inside target tissues."", can you determine the relation? product-of Regarding ""This study confirms the feasibility of using continuous measurement of AChE activity in CSF over prolonged periods, that << rivastigmine >> markedly inhibits CSF [[ AChE ]] after a single oral dose of 3 mg, and that the inhibition of central AChE is substantially greater than that of peripheral AChE or BuChE."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 265,"Similar to << gemfibrozil >>, clofibrate, another fibrate drug, also inhibited the expression of [[ iNOS ]]. Query: What is the relation? indirect-downregulator << Indomethacin >> activates carbonic anhydrase and antagonizes the effect of the specific [[ carbonic anhydrase ]] inhibitor acetazolamide, by a direct mechanism of action. Query: What is the relation? activator << Methylphenidate >>, an inhibitor of dopamine and norepinephrine transporters (DAT and [[ NET ]], respectively), is a standard treatment for ADHD. Query: What is the relation? inhibitor The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, [[ glutamine synthetase ]], glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings. Query: What is the relation? downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator << Risperidone >> is metabolized to its active metabolite, 9-hydroxyrisperidone, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4. Query: What is the relation? substrate Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS. Query: What is the relation? product-of Here, we have determined the molecular mechanism of this male-specific activation of the << Kcnk1 >> gene and characterized KCNK1 as a [[ phenobarbital ]]-inducible antihyperplasia factor. Query: What is the relation? indirect-upregulator Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner. Query: What is the relation? upregulator Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an [[ EP1 ]]-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. Query: What is the relation? agonist The putative << alpha 1L-adrenoceptor >> antagonist [[ JTH-601 ]], but not the alpha 1B-adrenoceptor antagonist chloroethylclonidine (10 microM) antagonized noradrenaline-induced contractions of SMA. Query: What is the relation? antagonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor In summary, the therapeutic effect of clozapine in reversing PPI impairment was mimicked by the << H(1) >> antagonist pyrilamine, while [[ pyrilamine ]] had a mixed effect on cognition. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 266,"One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of Consistent with these locations, << N-ethylmaleimide >>, an inhibitor of [[ ACS4 ]], inhibited ACS activity 47% in MAM and 28% in endoplasmic reticulum. what is the relation? inhibitor Effect of << ramelteon >> (TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor performance in mice. what is the relation? agonist Choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (<< BHMT >>) are 2 enzymes involved in [[ choline ]] oxidation. what is the relation? substrate << Phenobarbital >> (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including [[ erythropoietin ]], heme oxygenase-1 and vascular endothelial growth factor-a. what is the relation? indirect-upregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor Similarly, pretreatment with << sulindac sulfide >> blocks the ability of EGF to induce ERK1/2 and Bad phosphorylation, but also down-regulates total [[ Bad ]] but not ERK1/2 protein levels. what is the relation? indirect-downregulator Activating << glucocorticoid receptor >>-ERK signaling pathway contributes to [[ ginsenoside Rg1 ]] protection against β-amyloid peptide-induced human endothelial cells apoptosis. what is the relation? activator Second, C427A mutant human TOP2alpha, which exhibits reduced << ATPase >> activity, was shown to exhibit cross-resistance to all ATP-sensitive but not [[ ATP ]]-insensitive TOP2 poisons. what is the relation? downregulator The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (<< M/TPO-Ag >>) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis. what is the relation? upregulator << Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, [[ amines ]], and thiols, respectively. what is the relation? product-of In another experiment, << cyanopindolol >>, an antagonist of the [[ serotonin terminal autoreceptor ]], also prolonged the clearance of 5-HT from the CA3 region. what is the relation? antagonist Clinical studies in cancer patients treated with the new fluoropyrimidine analogue capecitabine (N4-pentoxycarbonyl-5'-5-fluorocytidine) have shown that plasma << 2'-deoxyuridine >> was significantly elevated after 1 week of treatment, consistent with inhibition of thymidylate synthase ([[ TS ]]). what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 267,"Consider the text ""The hyperglycemic effect of << m-CPBG >> central administration was blocked by pretreatment with ondansetron, a specific [[ 5-HT3 ]] receptor antagonist, indicating that the effects here obtained with m-CPBG were a result of its interaction with 5-HT3 receptors."". Can you identify the relation? agonist Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both MAO-A and << MAO-B >> by [[ tranylcypromine ]] together with the monoamine precursors."". Can you identify the relation? inhibitor Consider the text ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."". Can you identify the relation? upregulator Consider the text ""Moreover, recent in vitro studies suggest that << memantine >> abrogates [[ beta-amyloid ]] (Abeta) toxicity and possibly inhibits Abeta production."". Can you identify the relation? downregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (<< SHMT >>, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source."". Can you identify the relation? substrate Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and << xanthine oxidase >> was identified as the likely source of TES-stimulated [[ superoxide ]] production."". Can you identify the relation? product-of Consider the text ""Brain but not spinal << NR2B >> receptor is responsible for the anti-allodynic effect of an NR2B subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model."". Can you identify the relation? antagonist Consider the text ""In addition, << Silibinin >> caused an increase in [[ p53 ]] and p21 protein level as well as mRNA levels."". Can you identify the relation? indirect-upregulator Consider the text ""Our results demonstrated that << auranofin >> suppressed TLR4-mediated activation of transcription factors, NF-kappaB and IRF3, and expression of [[ COX-2 ]], a pro-inflammatory enzyme."". Can you identify the relation? indirect-downregulator Consider the text ""In contrast to parenteral delivery of rBChE, which currently requires posttranslational modification for good plasma stability, an unmodified aer-rBChE pretreatment given 1-40h prior to >1 LD50 of aer-<< paraoxon >> (Px) was able to prevent inhibition of circulating [[ cholinesterase ]] in a dose-dependent manner."". Can you identify the relation? activator Consider the text ""Selective inhibition of << cyclooxygenase 2 >> spares renal function and [[ prostaglandin ]] synthesis in cirrhotic rats with ascites."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 268,"Question: What is the relation in the sentence ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific).""? agonist Question: What is the relation in the sentence ""Risperidone is metabolized to its active metabolite, << 9-hydroxyrisperidone >>, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4.""? product-of Question: What is the relation in the sentence ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.""? upregulator Question: What is the relation in the sentence ""High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates [[ tuberin ]] and activates mTOR.""? downregulator Question: What is the relation in the sentence ""<< Gemfibrozil >>, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible nitric-oxide synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes.""? indirect-downregulator Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""In the presence of the system L inhibitor BCH, Na(+)-dependent l-alanine uptake in WKY and SHR PTE cells was inhibited by alanine, serine, and cysteine, which is consistent with << amino acid >> transport through [[ ASCT2 ]].""? substrate Question: What is the relation in the sentence ""Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while << TDCPP >> induced CYP3A37 and [[ CYP2H1 ]].""? indirect-upregulator Question: What is the relation in the sentence ""Although both intracellular and membrane << Cx43 >> pools were markedly reduced in cells released from contact inhibition by [[ TCDD ]], siRNA-mediated Cx43 knock-down was not sufficient to stimulate proliferation in contact-inhibited cells.""? inhibitor Question: What is the relation in the sentence ""In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and [[ cytochrome P450 ]], compared to the CCl4 only group.""? activator Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Clinical effects of << pranlukast >>, an oral [[ leukotriene receptor ]] antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial.""? antagonist Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma.""? agonist-activator Question: What is the relation in the sentence ""Herein, we report the identification and characterization of 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile (<< ESI-09 >>), a novel noncyclic nucleotide EPAC antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as [[ EPAC ]]-mediated insulin secretion in pancreatic β cells.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 269,"Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the << CB2 >> agonist AM1241 [[[ 1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole ]]], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects. Question: what is the relation? Answer: agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing GluR3(<< L507Y >>) mutant, but has synergistic effects with [[ lithium ]] on wild-type receptors. Question: what is the relation? Answer: activator The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Question: what is the relation? Answer: agonist-activator In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport. Question: what is the relation? Answer: upregulator Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the << dopamine D1 receptor >> antagonist SCH 39166 ([[ (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine ]]) and the dopamine D2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg). Question: what is the relation? Answer: antagonist Synthesis and antitumor activity of << 1,3,4-oxadiazole >> possessing 1,4-benzodioxan moiety as a novel class of potent [[ methionine aminopeptidase type II ]] inhibitors. Question: what is the relation? Answer: inhibitor The enzyme << cyclo-oxygenase >> catalyses the oxygenation of arachidonic acid, leading to the formation of [[ prostaglandins ]]. Question: what is the relation? Answer: product-of The concomitantly administered effects of << rifampicin >> on other drugs can result in their altered metabolism or transportation that are metabolised by [[ cytochromes P450 ]] or transported by p-glycoprotein in the gastrointestinal tract and liver. Question: what is the relation? Answer: substrate << PKC >> isoforms did show different sensitivity and selectivity for down-regulation by [[ I3A ]] and phorbol 12-myristate 13-acetate (PMA) in WEHI-231, HOP-92, and Colo-205 cells. Question: what is the relation? Answer: downregulator In conclusion, << IL-8 >> production and neutrophil infiltration are increased in high-[[ glucose ]] environment due to elevated ROS level and contributed to impaired wound healing in diabetic skin. Question: what is the relation? Answer: indirect-upregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor Epididymal tissue from wild-type mice responded in vitro to << noradrenaline >> and isoprenaline with increased glycerol release, reduced [[ IL-6 ]] release, and increased cAMP accumulation. Question: what is the relation? Answer: indirect-downregulator Other << 5-HT3 receptor >> antagonists also produced such a shift in the following antagonistic-potency order: [[ granisetron ]]> ondansetron=AS-8112>>metoclopramide. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 270,"Regarding the sentence ""Exposure of cells to 4mM << NaF >> for 24h induced [[ caspase-3 ]] activation, ultrastructural alterations, and resulted in the translocation of Bax to the mitochondria and the release of cytochrome c from the mitochondrial inter-membrane space into the cytosol, indicating that fluoride-mediated apoptosis is mitochondria-dependent."", what is the relation? activator Regarding the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator Regarding the sentence ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and [[ DNMT-3b ]]), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", what is the relation? downregulator Regarding the sentence ""<< Terfenadine >> and astemizole are chemically unrelated to [[ histamine H1-receptor ]] antagonists such as diphenhydramine and chlorpheniramine."", what is the relation? antagonist Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""The positive correlation between vitamin A and << immunoglobulin A >> concentrations might be the result of the [[ vitamin A ]] inductive effect during immunoglobulins A synthesis."", what is the relation? upregulator Regarding the sentence ""<< DBDCT >> up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of Bax/[[ Bcl-2 ]]."", what is the relation? indirect-upregulator Regarding the sentence ""The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB ([[ NF-κB ]]) p65 and p50 subunits."", what is the relation? indirect-downregulator Regarding the sentence ""<< ACTH >>-stimulated peak [[ cortisol ]], delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover."", what is the relation? product-of Regarding the sentence ""Block of << erg3 >> by [[ sertindole ]] also displayed a positive voltage-dependence."", what is the relation? inhibitor Regarding the sentence ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", what is the relation? agonist Regarding the sentence ""The M564G mutated << CrAT >> showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, [[ acetyl-CoA ]]."", what is the relation? substrate Regarding the sentence ""A series of << indazole arylsulfonamides >> were synthesized and examined as [[ human CCR4 ]] antagonists."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 271,"RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Please explain the relation. agonist-activator BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of << acetylcholine >>, an important neurotransmitter associated with memory, by blocking the enzyme [[ acetylcholinesterase ]]. Please explain the relation. substrate Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional [[ 5-HT1-like receptor ]], located to sensory nerves. Please explain the relation. activator << Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of [[ caspase 3 ]] and release of cytochrome c to the cytosol induced by DZN. Please explain the relation. indirect-upregulator Consistent with the weak transactivation activity of esterified-<< BM >> mediated by [[ rat GR ]], there were few side effects, evaluated by thymus involution and body weight loss, in an antigen-induced asthmatic model in rats. Please explain the relation. agonist However, phosphorylation of the p65/<< RelA >> subunit was clearly inhibited by [[ PSE ]] in stimulated cells. Please explain the relation. inhibitor We also shortly discuss the ongoing debate on whether << NO >> is the actual reaction product of [[ NOS ]] catalysis, as well as the phenomenon of NO-mediated autoinhibition. Please explain the relation. product-of METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (<< SB-207266 >>) on the cisapride mediated increase in plasma aldosterone (a [[ 5-HT(4) ]] mediated response) and orocaecal transit in 18 subjects. Please explain the relation. antagonist << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53. Please explain the relation. upregulator << Topiramate >> also partially depressed predominantly [[ AMPA-receptor ]]-mediated EPSCs, but with lower efficacy. Please explain the relation. indirect-downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Please explain the relation. substrate_product-of Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors ([[ Dkk1 ]] and Dkk2) of the pathway. Please explain the relation. downregulator The aim of this study was, therefore, to provide comparative binding characteristics of agonists (epinephrine, norepinephrine, isoproterenol, fenoterol, salbutamol, salmeterol, terbutalin, formoterol, broxaterol) and antagonists (propranolol, << alprenolol >>, atenolol, metoprolol, bisoprolol, carvedilol, pindolol, BRL 37344, CGP 20712, SR 59230A, CGP 12177, ICI 118551) at all three subtypes of [[ human beta-adrenergic receptors ]] in an identical cellular background. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 272,"A series of << phenolic acids >> and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]). Please explain the relation. inhibitor << LTD4 >> also induced expression of cysteinyl leukotriene receptor 1 ([[ CysLT(1)R ]]) and NF-κB p65 in the hippocampus and cortex. Please explain the relation. indirect-upregulator OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha (PPARalpha) and [[ PPARgamma ]] agonist, as a body-weight lowering, hypolipidemic and euglycemic agent. Please explain the relation. agonist Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor Clinical effects of << pranlukast >>, an oral [[ leukotriene receptor ]] antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial. Please explain the relation. antagonist Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, [[ c-jun-N-terminal kinase ]], p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α. Please explain the relation. activator Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. Please explain the relation. product-of Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin. Please explain the relation. downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator Compound 6 stimulated << OATP1B3 >>-mediated [[ estradiol 17β-glucuronide ]] uptake by increasing the apparent affinity of OATP1B3 for its substrate. Please explain the relation. substrate Prostaglandin E1, E2, STA2 (a stable analogue of << thromboxane A2 >>), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. Please explain the relation. indirect-downregulator In addition to this pronounced loss of function, << M1766L >> also showed a 10-fold increase in the persistent late [[ sodium ]] current. Please explain the relation. upregulator In complementary RNA (cRNA)-injected Xenopus laevis oocytes, << rifamycin SV >> (10 micromol/L) cis-inhibited human organic anion transporting polypeptide C (SLC21A6) (OATP-C), human organic anion transporting polypeptide 8 (SLC21A8) (OATP8), [[ human organic anion transporting polypeptide B ]] (SLC21A9) (OATP-B), and human organic anion transporting polypeptide A (SLC21A3) (OATP-A) mediated BSP uptake by 69%, 79%, 89%, and 57%, respectively, as compared with uptake into control oocytes. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 273,"Consider the text ""Combination treatment with the selective << 5-HT1A >> antagonist [[ WAY100635 ]] produced a dose-dependent augmentation of venlafaxine-induced (3-30 mg/kg s.c) extracellular 5-HT concentrations, but had no further effect on NA above that produced by venlafaxine alone."". Can you identify the relation? antagonist Consider the text ""Differences in magnitude of Na(+)-dependent << l-alanine >> uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."". Can you identify the relation? upregulator Consider the text ""We conclude that << DeltaKPQ >> interacts differently with [[ flecainide ]] than with WT, leading to increased block and slowed recovery, especially for late I(Na)."". Can you identify the relation? inhibitor Consider the text ""CONCLUSIONS: Total vitamin B6 is abnormally high in autism, consistent with previous reports of an impaired << pyridoxal kinase >> for the conversion of [[ pyridoxine ]] and pyridoxal to PLP."". Can you identify the relation? substrate Consider the text ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."". Can you identify the relation? downregulator Consider the text ""In support of the hypothesis that << TCDD >> decreases canonical [[ Wnt ]] signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD."". Can you identify the relation? indirect-downregulator Consider the text ""Such model of << Nox4 >> activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i.e., its potential redox regulation, and could also define new therapeutic targets in diseases in which [[ quinones ]] and Nox4 are implicated."". Can you identify the relation? activator Consider the text ""We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as ascorbate peroxidase ([[ APX ]])."". Can you identify the relation? product-of Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."". Can you identify the relation? agonist Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""This initial action was accompanied by up-regulation of cyclooxygenase-2 (<< COX-2 >>), an important inflammation marker within 1h after [[ TCDD ]] treatment."". Can you identify the relation? indirect-upregulator Consider the text ""Our observations indicate an << OCT >>-mediated transmembrane transport of [[ [3H]-MPP+ ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 274,"Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists."", what is the relation? antagonist Regarding the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53."", what is the relation? upregulator Regarding the sentence ""The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition."", what is the relation? agonist Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and << xanthine oxidase >> was identified as the likely source of TES-stimulated [[ superoxide ]] production."", what is the relation? product-of Regarding the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator Regarding the sentence ""<< Dexamethasone >> (DEX) inhibited the anti-CD3-induced production of [[ IL-4 ]], IL-5 and IFN-gamma in all 20 clones tested."", what is the relation? indirect-downregulator Regarding the sentence ""Effects of inhibition of << urokinase-type plasminogen activator >> (u-PA) by [[ amiloride ]] in the cornea and tear fluid of eyes irradiated with UVB."", what is the relation? inhibitor Regarding the sentence ""Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h."", what is the relation? indirect-upregulator Regarding the sentence ""<< L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and [[ L-threonine ]] to yield pyruvate or 2-oxobutyrate."", what is the relation? substrate Regarding the sentence ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and [[ DNMT-3b ]]), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", what is the relation? downregulator Regarding the sentence ""Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα ([[ IκBα ]]) kinase, and inositol requiring enzyme 1α."", what is the relation? activator Regarding the sentence ""<< GnRH >> pulse frequency-dependent stimulation of FSHβ transcription is mediated via activation of [[ PKA ]] and CREB."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 275,"A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase ([[ CEase ]]) and acetylcholinesterase (AChE). what is the relation? inhibitor FCEO significantly inhibited << nitric oxide >> (NO) and prostaglandin E2 (PGE2) by suppressing the protein expression of inducible nitric oxide synthase ([[ iNOS ]]) and cyclooxygenase (COX)-2, respectively. what is the relation? indirect-downregulator The efficacy of << astemizole >>, a new, long acting, oral [[ histamine H1-receptor ]] antagonist was compared to placebo for the treatment of allergic rhinitis and conjunctivitis during the grass pollen season of 1982. what is the relation? antagonist << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. what is the relation? agonist-activator These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. what is the relation? upregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). what is the relation? substrate_product-of << 6-DHSG >> was metabolised by GSH to form a GSH conjugate (GS-6-DHSG) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of glutathione-S-transferase ([[ GST ]]). what is the relation? substrate These results indicate that << phillyrin >> prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through [[ LKB1 ]]/AMPK activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity. what is the relation? activator << Phosphatidylserine >> (PtdSer) is made in mammalian cells by two PtdSer synthases, PSS1 and [[ PSS2 ]]. what is the relation? product-of Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of [[ HO-1 ]] activity. what is the relation? indirect-upregulator Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of [[ VEGF ]] and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells. what is the relation? downregulator << 2-(2-Aminoethyl)-quinoline >> (D-1997): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery. what is the relation? agonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor While << sophocarpine >> treatment resulted in: significant improvement of steatosis (>50% decrease), decrease of [[ leptin ]] expression (<0.57-fold) and increase of adiponectin expression (>1.48-fold). what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 276,"Given the text ""Similarly, << pelargonidin >> induced the expression of [[ CYP1A1 ]] mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin (TCDD), the most potent activator of AhR."", describe the relation. indirect-upregulator Given the text ""<< ACTH >>-stimulated peak cortisol, [[ delta cortisol ]], and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover."", describe the relation. product-of Given the text ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", describe the relation. agonist-activator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", describe the relation. substrate_product-of Given the text ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."", describe the relation. upregulator Given the text ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", describe the relation. downregulator Given the text ""We discovered that each RSPO alone or in combination partially rescues << TCDD >> inhibition of both canonical [[ Wnt ]] signaling and prostatic bud formation."", describe the relation. indirect-downregulator Given the text ""A novel class of << quinoxalines >> has been discovered as antagonists of the IgG:[[ FcRn ]] protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen."", describe the relation. antagonist Given the text ""2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", describe the relation. agonist Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""An increase in the ADP/<< ATP >> ratio opens [[ K(ATP) channels ]], leading to membrane hyperpolarization."", describe the relation. activator Given the text ""Again, inhibition of the actin-activated myosin Mg2+-ATPase and << myosin >> filament assembly by [[ felodipine ]] and the p-chloro analogue could be reversed by raising the calmodulin concentration."", describe the relation. inhibitor Given the text ""These findings demonstrate that << PEPT2 >> is the primary transporter responsible for [[ cefadroxil ]] uptake in the choroid plexus."", describe the relation. substrate Given the text ""100 micromol/L << rifampicin >> inhibited OATP-C- and OATP8-, OATP-B- and [[ OATP-A ]]-mediated BSP uptake by 66%, 96%, 25%, and 49%, respectively."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 277,"The identification of the succinate receptor << SUCNR1 >> in platelets is of particular interest, because physiologically relevant concentrations of [[ succinate ]] were shown to potentiate the effect of low doses of a variety of platelet agonists. what is the relation? agonist The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. what is the relation? agonist-activator Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues. what is the relation? product-of Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]. what is the relation? upregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor << zRetSat A >> also saturated the 13-14 or 7-8 double bonds of [[ all-trans-3,4-didehydroretinol ]] (vitamin A2), a second endogenous form of vitamin A in zebrafish. what is the relation? substrate Treatment with << carvedilol >> is associated with a reversal of abnormal regulation of HIF-1alpha and [[ VEGF ]] in the failing ventricular myocardium. what is the relation? indirect-downregulator On the other hand, in patients with a mean serum << carvedilol >> level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l. what is the relation? downregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of These findings suggest that << S1P >> activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including [[ alkaline phosphatase ]], probably relating to the inhibition of osteoclast formation and the mineralization, respectively. what is the relation? indirect-upregulator Both tolbutamide and << gliclazide >> stimulated [[ phospholipase C ]] activity; however, only gliclazide did so independently of its activity at K(ATP) channels, and this activity was partially inhibited by pertussis toxin. what is the relation? activator << Phenformin >> causes lactic acidosis in clinical situations due to inhibition of [[ mitochondrial respiratory chain complex I ]]. what is the relation? inhibitor In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with [[ rauwolscine ]], phentolamine, and idazoxan. what is the relation? antagonist Dimethylarginine dimethylaminohydrolase (<< DDAH >>) metabolizes asymmetric [[ dimethylarginine ]] to generate L-citrulline and is present in large quantities in the kidney. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 278,"In reference to ""Our results suggest that arsenite can potentiate EDHF-type relaxations via a mechanism that is dependent on hydrogen peroxide, thus demonstrating that dismutation of the << superoxide >> anion generated by [[ NADPH oxidase ]] can potentially offset loss of NO bioavailability under conditions of reduced eNOS activity."", what is the relation? product-of In reference to ""The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists terfenadine, astemizole, loratadine, and [[ acrivastine ]] are reviewed."", what is the relation? antagonist In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""<< Pelargonidin >> activates the [[ AhR ]] and induces CYP1A1 in primary human hepatocytes and human cancer cell lines HepG2 and LS174T."", what is the relation? activator In reference to ""Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats."", what is the relation? upregulator In reference to ""Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing [[ NF-κB ]] activity and induction of Nrf2-dependent HO-1 activity."", what is the relation? downregulator In reference to ""In muscle and liver, << TCDD >> (10 ng/kg/day) induced increases in methylation and decreases in mRNA expression of [[ Igf2r ]]."", what is the relation? indirect-downregulator In reference to ""Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist [[ formoterol ]] [eformoterol]."", what is the relation? agonist In reference to ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and << 5-trifluorothymidine >> (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase ([[ TS ]])."", what is the relation? inhibitor In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""Kinetic constants of the mutant << CrAT >> showed modification in favor of longer [[ acyl-CoAs ]] as substrates."", what is the relation? substrate In reference to ""<< Cortisol >> and IFNT stimulated endometrial [[ HSD11B1 ]] expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium."", what is the relation? indirect-upregulator In reference to ""Furthermore, << nobiletin >> could inhibit HGF-induced the membrane localization of phosphorylated c-Met, [[ ERK2 ]], and Akt, but not phosphorylated JNK1/2 and p38."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 279,"<< Doxycycline >> was shown to decrease cerebral MMP-9 activities and angiogenesis induced by [[ vascular endothelial growth factor ]] (VEGF). Query: What is the relation? inhibitor << Pranlukast >>, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from [[ leukotriene receptor ]] antagonism. Query: What is the relation? antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor These effects were fully counteracted by dietary << phenolics >> which inhibited ROS overproduction and GSH consumption, rendered the reactive transcription of glutathione-associated enzymes unnecessary and blocked the intracellular signals leading to the overexpression and rearrangement of [[ p66Shc ]] signalling molecule. Query: What is the relation? indirect-downregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and [[ glutathioneperoxidase ]] (GPx) activities, while increased catalase (CAT) activity compared with the control. Query: What is the relation? downregulator << Amitriptyline >> is a TrkA and [[ TrkB ]] receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Query: What is the relation? agonist First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the << ATP-binding cassette transporter A1 >> (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner. Query: What is the relation? product-of The << bupropion >> metabolic ratio appears to detect known differences in [[ CYP2B6 ]] activity associated with genetic polymorphism, across different ethnic groups. Query: What is the relation? substrate Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(<< WAF1 >>/CIP1) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2. Query: What is the relation? indirect-upregulator CONCLUSIONS: Our results show that << indomethacin >>, a known cyclooxygenase (COX) inhibitor, is also an activator of [[ CA ]]. Query: What is the relation? activator CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme. Query: What is the relation? upregulator Correlating with FSHβ activation, both PKA activity and levels of pCREB were increased to a greater extent by low compared with high << GnRH >> pulse frequencies, and the induction of [[ pCREB ]] was also attenuated by overexpression of DNPKA at both low and high pulse frequencies. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 280,"In reference to ""During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce << prostaglandins >> (PG) via [[ PG synthase 2 ]] (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1)."", what is the relation? product-of In reference to ""The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB ([[ NF-κB ]]) p65 and p50 subunits."", what is the relation? indirect-downregulator In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""The << TSA >>-induced [[ uc002mbe.2 ]] expression was positively correlated with the apoptotic effect of TSA in HCC cells."", what is the relation? indirect-upregulator In reference to ""BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific << alpha2-adrenoceptor >> agonists of the type such as [[ dexmedetomidine ]]."", what is the relation? agonist In reference to ""The selective << beta1AR >> antagonists atenolol and [[ metoprolol ]] blocked isoproterenol-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively."", what is the relation? antagonist In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 ([[ CDK2 ]]), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""Interestingly, << gemfibrozil >> strongly inhibited the activation of NF-kappaB, AP-1, and [[ C/EBPbeta ]] but not that of GAS in cytokine-stimulated astroglial cells."", what is the relation? inhibitor In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/[[ CIP1 ]]) and p53."", what is the relation? upregulator In reference to ""<< Carboxylesterases >> hydrolyze esters, amides, and [[ thioesters ]] to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively."", what is the relation? substrate In reference to ""<< Indomethacin >> abolished the inhibitory effect of acetazolamide on CA I and [[ CA II ]]."", what is the relation? activator In reference to ""Design and synthesis of << bicyclic pyrazinone and pyrimidinone amides >> as potent [[ TF ]]-FVIIa inhibitors."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 281,"<< Ramelteon >> (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin [[ MT(1) ]]/MT(2) receptor agonist. Question: what is the relation? Answer: agonist In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives ([[ AA-861 ]], tBuBHQ, tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines. Question: what is the relation? Answer: activator These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by SP-[[ NK-1R ]] related pathway in mouse pancreatic acinar cells. Question: what is the relation? Answer: product-of Because clinical studies investigating interactions between garlic and << human immunodeficiency virus protease >> inhibitors [[ saquinavir ]] and ritonavir have already been performed, we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first-pass intestinal metabolism changes. Question: what is the relation? Answer: inhibitor Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin ([[ TCDD ]]), the most potent activator of AhR. Question: what is the relation? Answer: upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a [[ BRCA2 ]] mutation. Question: what is the relation? Answer: downregulator The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists SB224289 (300 microg/kg; 5-HT1B), << BRL15572 >> (300 microg/kg; [[ 5-HT1D ]]), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C). Question: what is the relation? Answer: antagonist Block of human NaV1.5 << sodium channels >>[[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin. Question: what is the relation? Answer: substrate The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator On study day 1, << candoxatril >> acutely increased plasma [[ ANP ]] levels, suppressed aldosterone and decreased right atrial and pulmonary capillary wedge pressures. Question: what is the relation? Answer: indirect-upregulator Dexamethasone (<< DXM >>) decreased the expression of [[ CXCL-8 ]], VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (1400W), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and iNOS. Question: what is the relation? Answer: indirect-downregulator The identity of the lung << beta-ADHs >> was further demonstrated by their characteristic pH-activity profiles for ethanol oxidation, Km values for NAD and ethanol, and inhibition by [[ 4-methylpyrazole ]] or 1,10-phenanthroline. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 282,"Take together, our results demonstrated that << juglone >> might induce the apoptosis in LNCaP cell via down-regulation of [[ AR ]] expression. Question: what is the relation? Answer: indirect-downregulator 5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (<< F3(d)Thd >>) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of [[ thymidylate synthase ]] (TS). Question: what is the relation? Answer: inhibitor BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific << alpha2-adrenoceptor >> agonists of the type such as [[ dexmedetomidine ]]. Question: what is the relation? Answer: agonist BACKGROUND & AIMS: Of the 2 genes (<< MAT1A >>, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes [[ S-adenosylmethionine ]], MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues. Question: what is the relation? Answer: product-of << Statins >> increase p21 through inhibition of histone deacetylase activity and release of promoter-associated [[ HDAC1/2 ]]. Question: what is the relation? Answer: upregulator The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator << Plerixafor >>, a [[ CXCR4 ]] antagonist for the mobilization of hematopoietic stem cells. Question: what is the relation? Answer: antagonist One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, << EC 2.1.2.1 >>) with [[ glycine ]] (Gly) as one-carbon (1-C) source. Question: what is the relation? Answer: substrate One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Consumption of << alcohol >> for 8weeks induced severe liver damage with increases in prognostic indicators such as [[ aspartate transaminase ]], alanine transaminase in serum whereas co-administration of CNF suppressed their increases. Question: what is the relation? Answer: indirect-upregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor << 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone >> inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and [[ Nrf-2 ]]-dependent heme oxygenase-1 induction. Question: what is the relation? Answer: activator Previously, we showed that the << human kappa-opioid receptor >> (hkor) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged [[ U50,488H ]] treatment. Question: what is the relation? Answer: downregulator The results suggest that individuals with high Vmax beta 2-ADH and deficient in low-Km mitochondrial << ALDH2 >>, accounting for approximately 45% of the Chinese population, may end up with acetaldehyde accumulation during [[ alcohol ]] consumption, rendering them vulnerable to tissue injury caused by this highly reactive and toxic metabolite. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 283,"Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by << TCDD >>, siRNA-mediated [[ Cx43 ]] knock-down was not sufficient to stimulate proliferation in contact-inhibited cells. Question: what is the relation? Answer: downregulator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53. Question: what is the relation? Answer: upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Question: what is the relation? Answer: agonist-activator Conversely, opioid antagonists such as << naloxone >> and naltrexone (which bind to non-selectively [[ opioid receptors ]]) have been shown to decrease alcohol consumption under various experimental conditions. Question: what is the relation? Answer: antagonist << Risperidone >> is metabolized to its active metabolite, 9-hydroxyrisperidone, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4. Question: what is the relation? Answer: substrate Independent of dietary choline, supplemental << Met >> increased hepatic [[ BHMT ]] activity approximately 30%. Question: what is the relation? Answer: activator << Amitriptyline >> is a TrkA and [[ TrkB ]] receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Question: what is the relation? Answer: agonist The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (<< TNF-α >>), nuclear factor kappa B (NF-κB) genes expression in [[ cisplatin ]] injected rats. Question: what is the relation? Answer: indirect-downregulator << PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, [[ Bak ]], cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. Question: what is the relation? Answer: indirect-upregulator Specificity of << zebrafish retinol saturase >>: formation of [[ all-trans-13,14-dihydroretinol ]] and all-trans-7,8- dihydroretinol. Question: what is the relation? Answer: product-of One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of << Enalkiren >> has been shown to produce dose-related suppression of plasma renin activity (PRA) and [[ angiotensin II ]] when administered intravenously. Question: what is the relation? Answer: inhibitor Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor 2 In a chronic transfection model using CHO-K1 cells, << cisapride >> inhibited [[ HERG ]] tail currents after a step to +25 mV with similar potency at room and physiological temperatures (IC50 16. 4 nM at 20-22 degrees C and 23.6 nM at 37 degrees C). Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 284,"Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Question: what is the relation? Answer: upregulator << Genistin >> decreased [[ myosin light chain kinase ]] (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects. Question: what is the relation? Answer: indirect-downregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of In another experiment, << cyanopindolol >>, an antagonist of the [[ serotonin terminal autoreceptor ]], also prolonged the clearance of 5-HT from the CA3 region. Question: what is the relation? Answer: antagonist The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist [[ salbutamol ]] 8 mg (SAL), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors. Question: what is the relation? Answer: agonist During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce << prostaglandins >> (PG) via [[ PG synthase 2 ]] (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1). Question: what is the relation? Answer: product-of Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor The present study examined the effect of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), on << VMAT2 >> activity by measuring adenosine triphosphate-dependent [[ [(3)H]dopamine ]] uptake into synaptic vesicles prepared from rat striatum. Question: what is the relation? Answer: substrate In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins ([[ MeCP-2 ]], MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Question: what is the relation? Answer: downregulator Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers ([[ sulforaphane ]], tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments. Question: what is the relation? Answer: activator Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>[[ parathion ]]>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent. Question: what is the relation? Answer: inhibitor Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression and improved glucose tolerance parallel to [[ insulin ]] sensitivity in obese mice. Question: what is the relation? Answer: indirect-upregulator In monocytes, both EPA and << DHA >> increased [[ interleukin (IL)-10 ]] without affecting tumor necrosis factor (TNF)-α and IL-6. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",6,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",upregulator 285,"Regarding ""2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", can you determine the relation? agonist Regarding ""<< Topiramate >> also partially depressed predominantly [[ AMPA-receptor ]]-mediated EPSCs, but with lower efficacy."", can you determine the relation? indirect-downregulator Regarding ""In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and << aniline 4-hydroxylase >> activity and cytochrome P450, compared to the [[ CCl4 ]] only group."", can you determine the relation? activator Regarding ""<< CYP1A1 >> and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", can you determine the relation? upregulator Regarding ""<< Betaxolol >>, a beta(1)-adrenoceptor antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other [[ beta-adrenoceptor ]] antagonists."", can you determine the relation? antagonist Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", can you determine the relation? substrate_product-of Regarding ""Here, we show that one << BLT >>, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of [[ SR-BI ]] (IC(50) approximately 55-60 microM)."", can you determine the relation? inhibitor Regarding ""<< Adenylosuccinate synthetase >> (AdSS) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP."", can you determine the relation? product-of Regarding ""These results indicate a major role of << CYP2B6 >> in [[ ketamine ]] N-demethylation in vitro and a significant impact of the CYP2B6*6 allele on enzyme-ketamine binding and catalytic activity."", can you determine the relation? substrate Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal << NGF >>, BDNF and ChAT that was eliminated by [[ olanzapine ]] treatment."", can you determine the relation? indirect-upregulator Regarding ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the [[ methyl CpG-binding proteins ]] (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", can you determine the relation? downregulator Regarding ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", can you determine the relation? agonist-activator Regarding ""<< PTP >> inhibition by [[ hisphosphonates ]] or vanadate was diminished by the metal chelating agent EDTA, or by the reducing agent dithiothreitol, suggesting that a metal ion and the oxidation of a cysteine residue are required for full inhibition."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 286,"Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the << singlet oxygen >> (1O2) donor chloramine T (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin. Please explain the relation. downregulator Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, [[ survivin ]], cyclin D1, MMP7, and c-Myc. Please explain the relation. indirect-downregulator << Noradrenaline >> and phenylephrine ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively. Please explain the relation. agonist The TXM peptides were effective in inhibiting << AuF >>-induced MAPK, JNK and p38([[ MAPK ]]) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation. Please explain the relation. activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration. Please explain the relation. upregulator BACKGROUND & AIMS: Of the 2 genes (<< MAT1A >>, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes [[ S-adenosylmethionine ]], MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues. Please explain the relation. product-of Nizatidine (<< LY139037 >>), a selective [[ histamine H2-receptor ]] antagonist, is a potent inhibitor of gastric acid secretion. Please explain the relation. antagonist In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Please explain the relation. agonist-activator << DBDCT >> up-regulated the expression of [[ Bax ]], down-regulated the expression of Bcl-2, and significantly increased the ratio of Bax/Bcl-2. Please explain the relation. indirect-upregulator Experimental cystathioninuria was induced in rats by administration of the << cystathionine gamma-lyase >> inhibitor, [[ D,L-propargylglycine ]]. Please explain the relation. inhibitor One major route involves the tetrahydrofolate (THF)-dependent activities of the << glycine decarboxylase complex >> (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) with glycine ([[ Gly ]]) as one-carbon (1-C) source. Please explain the relation. substrate BACKGROUND: Peripheral inflammatory pain is associated with an upregulation of spinal cord COX-2 (<< cyclooxygenase-2 >>), with a subsequent increase in central [[ prostaglandin E2 ]] (PGE2) levels associated with the development of hyperalgesia. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 287,"Question: What is the relation in the sentence ""These results indicate that << U50,488H >>-induced down-regulation of the [[ hkor ]] involves GRK-, arrestin-2-, dynamin-, rab5-, and rab7-dependent mechanisms and receptors seem to be trafficked to lysosomes and proteasomes for degradation.""? downregulator Question: What is the relation in the sentence ""BACKGROUND & AIMS: Of the 2 genes (MAT1A, << MAT2A >>) encoding methionine adenosyltransferase, the enzyme that synthesizes [[ S-adenosylmethionine ]], MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues.""? product-of Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""These results indicate that, similar to the sulfonylureas, mitiglinide is highly specific to the Kir6.2/SUR1 complex, i.e., the pancreatic beta-cell << K(ATP) channel >>, and suggest that [[ mitiglinide ]] may be a clinically useful anti-diabetic drug.""? agonist Question: What is the relation in the sentence ""PIP5K1B encodes << phosphatidylinositol 4-phosphate 5-kinase β type I >> (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates [[ phosphatidylinositol 4-phosphate ]] [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].""? substrate Question: What is the relation in the sentence ""In the present study, we compared the pharmacology of (+/-)pindolol, WAY-100635 (a 5-HT(1A) antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and << isamoltane >> (a [[ 5-HT(1B) ]] antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat.""? antagonist Question: What is the relation in the sentence ""Similar to << gemfibrozil >>, clofibrate, another fibrate drug, also inhibited the expression of [[ iNOS ]].""? indirect-downregulator Question: What is the relation in the sentence ""The effects of << theophylline >> (unspecific [[ PDE ]] inhibitor), vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor) and the PDE5 inhibitors zaprinast and E 4021 were weak.""? inhibitor Question: What is the relation in the sentence ""Quantitative real-time polymerase chain reaction analysis showed that following the exposure of cells to << SiO(2) >> NPs, the messenger RNA level of apoptotic genes ([[ caspase-3 ]] and caspase-9) were upregulated in a dose-dependent manner.""? indirect-upregulator Question: What is the relation in the sentence ""<< CCl(4) >> administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and [[ cyclooxygenase-2 ]] (COX-2).""? activator Question: What is the relation in the sentence ""Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512).""? upregulator Question: What is the relation in the sentence ""<< Sorafenib >> and sunitinib are synthetic, orally active agents shown to directly inhibit vascular endothelial growth factor receptors -2 and -3 (VEGFR-2, [[ VEGFR-3 ]]) and platelet-derived growth factor receptor beta (PDGFR-beta), while temsirolimus is an mTOR inhibitor.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 288,"In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""These results indicate transcription of << FDX1 >> is regulated by the NR5A family and [[ cAMP ]] signaling, and participates in steroid hormone production in ovarian granulosa cells."", what is the relation? indirect-upregulator In reference to ""Glycylsarcosine coadministration could inhibit the uptake of << cefadroxil >> in [[ PEPT2 ]](+/+) mice (p < 0.01) but not PEPT2(-/-) mice."", what is the relation? substrate In reference to ""As determined by Western and Northern blot analyses, << 5 alpha-NET >> inhibited the P4-induced [[ UG ]] gene expression in a dose-dependent manner."", what is the relation? indirect-downregulator In reference to ""Subsequent analysis revealed that << cucurbitacin I >> strongly activates RhoA and the [[ Rho ]] effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers."", what is the relation? activator In reference to ""The positive correlation between << vitamin A >> and immunoglobulin A concentrations might be the result of the vitamin A inductive effect during [[ immunoglobulins A ]] synthesis."", what is the relation? upregulator In reference to ""Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats."", what is the relation? downregulator In reference to ""We conclude that alprenolol and << BAAM >> are competitive slowly reversible [[ beta 1-adrenoceptor ]] antagonists on rat left atria."", what is the relation? antagonist In reference to ""<< Indomethacin >> inhibited both [[ hCOX-1 ]] and hCOX-2, whereas NS-398 and Dup-697 selectively inhibited hCOX-2."", what is the relation? inhibitor In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""Prazosin (nonselective << alpha(1)-adrenoceptor >> antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively)."", what is the relation? agonist In reference to ""<< ATP-binding cassette transporter A1 >> is involved in hepatic [[ alpha-tocopherol ]] secretion."", what is the relation? product-of In reference to ""Adult ovariectomised rats were divided into six groups and injected either with vehicle or a single dose of oestradiol, a selective ERα agonist-PPT [4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol], a selective ERβ agonist-DPN [2,3-bis(4-hydroxyphenyl)-propionitrile], a selective << ERα >> antagonist-[[ MPP ]] [1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride] or a selective ERβ antagonist-PHTPP (4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 289,"In reference to ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively."", what is the relation? upregulator In reference to ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased [[ superoxide dismutase ]] (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control."", what is the relation? downregulator In reference to ""These results suggest that << CYP2B6 >> genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of [[ bupropion ]]."", what is the relation? substrate In reference to ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers << DEX >> inhibited IL-2 production partially and enhanced [[ IL-2R alpha ]] expression and proliferation."", what is the relation? indirect-upregulator In reference to ""OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting << alpha2 adrenergic receptor >> (AR) agonist ([[ dexmedetomidine ]])."", what is the relation? agonist In reference to ""A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and [[ acetylcholinesterase ]] (AChE)."", what is the relation? inhibitor In reference to ""<< [6]-Gingerol >> derived from Zingiber officinale Roscoe (ginger) was identified as a novel [[ angiotensin II type 1 receptor ]] antagonist, with an IC50 value of 8.173 µM."", what is the relation? antagonist In reference to ""To begin to examine whether these changes are mediated by alterations in gene expression for tryptophan hydroxylase (<< TPH >>), the rate-limiting enzyme in [[ 5-HT ]] biosynthesis, we quantitated its mRNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR)."", what is the relation? product-of In reference to ""Next, we examined the role of Rho family GTPases in the << ceramide >>-induced signalling to [[ SRE ]] activation."", what is the relation? activator In reference to ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""As revealed by glucose oxidase (GOD) and radioimmunoassay (RIA), both << dimethyldiguanide >> (DC, 0.6gkg(-1)d(-1)) and CPS (0.3, 0.6, 1.2gkg(-1)d(-1)) treatments significantly resulted in down-regulation of blood glucose and [[ insulin ]] levels in serum, while the levels of oxidative stress markers were markedly lowered through ELISA assay."", what is the relation? indirect-downregulator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Correlating with FSHβ activation, both << PKA >> activity and levels of pCREB were increased to a greater extent by low compared with high [[ GnRH ]] pulse frequencies, and the induction of pCREB was also attenuated by overexpression of DNPKA at both low and high pulse frequencies."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 290,"Question: What is the relation in the sentence ""In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of << cAMP >> to AMP by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase.""? substrate Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].""? agonist-activator Question: What is the relation in the sentence ""<< All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]].""? upregulator Question: What is the relation in the sentence ""Differentiating the roles of mGlu2 and mGlu3 receptors using << LY541850 >>, an [[ mGlu2 ]] agonist/mGlu3 antagonist.""? agonist Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and [[ BT-05 ]] and BT-03 possessing asymmetric structure.""? activator Question: What is the relation in the sentence ""Since gemfibrozil is known to activate peroxisome proliferator-activated receptor-alpha (PPAR-alpha), we investigated the role of PPAR-alpha in << gemfibrozil >>-mediated inhibition of [[ iNOS ]].""? inhibitor Question: What is the relation in the sentence ""<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β ([[ GSK-3β ]]) signaling pathway.""? indirect-downregulator Question: What is the relation in the sentence ""Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent [[ HO-1 ]] activity.""? downregulator Question: What is the relation in the sentence ""Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index.""? product-of Question: What is the relation in the sentence ""These results showed that << WNT6 >> and Cav1 are upregulated by chemotherapeutics and enhance the resistance of GC cells to [[ anthracycline ]] drugs.""? indirect-upregulator Question: What is the relation in the sentence ""In further studies, the diuretic effects of the << CB1 >> agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with [[ rimonabant ]], but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)].""? antagonist Question: What is the relation in the sentence ""The observed inhibition on IFN-gamma, << GM-CSF >>, and IL-3 mRNA was blocked by the selective beta2AR antagonist ICI 118,551 (10(-6) M) and by [[ timolol ]] (10(-6) M), a nonselective antagonist.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 291,"Selective antagonism of << GluR5 >> kainate-receptor-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons. Please explain the relation. antagonist These results indicate that phillyrin prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that << phillyrin >> is a novel [[ AMPK ]] activator with a role in the prevention and treatment of obesity. Please explain the relation. activator Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive [[ oxygen ]] species (ROS), which are capable of initiating and promoting carcinogenesis. Please explain the relation. product-of In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the << PGE1 >> mediated stimulation of [[ Na,K-ATPase beta ]] subunit gene transcription includes the stimulatory effect of 17-phenyl trinor PGE2, as well as the inhibitory effects of SC-51089. Please explain the relation. indirect-upregulator The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity. Please explain the relation. agonist RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Please explain the relation. agonist-activator The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of << acetylcholinesterase >> (AChE) in the nervous system, which leads to increased synaptic [[ acetylcholine ]] levels. Please explain the relation. substrate Colonic cyclooxygenase-2 and interkeukin-1beta mRNA and spinal << c-FOS >> mRNA expression were significantly down-regulated by [[ ATB-429 ]], but not by mesalamine. Please explain the relation. indirect-downregulator In study 1, cyclic ewes received vehicle, cortisol, PF 915275 (PF; a selective inhibitor of HSD11B1), cortisol and PF, << meloxicam >> (a selective inhibitor of [[ PTGS2 ]]), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus. Please explain the relation. inhibitor The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase ([[ GPx ]]) activities, while increased catalase (CAT) activity compared with the control. Please explain the relation. downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of G6pc2 deletion resulted in a leftward shift in the dose-response curve for << glucose >>-stimulated [[ insulin ]] secretion (GSIS). Please explain the relation. upregulator << Irinotecan >> (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting [[ DNA topoisomerase I ]] (Topo I). Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 292,"Regarding the sentence ""Meanwhile, autophagy was detected as early as 12 h after an exposure to low-dose << dioscin >>, as indicated by an up-regulated expression of [[ LC3-II ]] and beclin-1 proteins."", what is the relation? indirect-upregulator Regarding the sentence ""Suppression of Src/<< ERK >> and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells."", what is the relation? downregulator Regarding the sentence ""Dasatinib (<< BMS-354825 >>) is a novel orally bioavailable SRC/[[ ABL ]] inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML)."", what is the relation? inhibitor Regarding the sentence ""With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited [[ p16 ]] mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control."", what is the relation? indirect-downregulator Regarding the sentence ""The positive correlation between vitamin A and immunoglobulin A concentrations might be the result of the << vitamin A >> inductive effect during [[ immunoglobulins A ]] synthesis."", what is the relation? upregulator Regarding the sentence ""In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to << AMP >> by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase."", what is the relation? product-of Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""In the rabbit pulmonary artery, << rilmenidine >> and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan."", what is the relation? antagonist Regarding the sentence ""Thus, << amitriptyline >> acts as a TrkA and [[ TrkB ]] agonist and possesses marked neurotrophic activity."", what is the relation? agonist Regarding the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [[[ PI(4)P ]]] to generate phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]."", what is the relation? substrate Regarding the sentence ""These results indicate that << phenobarbital >> treatment induces [[ KCNK1 ]] to elicit a male-specific and growth-suppressing signal."", what is the relation? activator Regarding the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator Regarding the sentence ""Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and [[ 7-hydroxyflavone ]]; these chemicals induced Type I spectral changes with low Ks values."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 293,"Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (<< 1400W >>), a selective inhibitor of iNOS, decreased the expression of E-selectin, [[ VEGF ]], and iNOS. Please explain the relation. indirect-downregulator OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha ([[ PPARalpha ]]) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent. Please explain the relation. agonist The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator Only pMPPI [<< 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride >>], a selective [[ 5-HT(1A) ]] antagonist, was effective in inhibiting all 5-HT syndrome behaviors produced by lisuride, whereas pMPPI was without effect on any behavior induced by LSD. Please explain the relation. antagonist 4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant [[ UGTs ]]. Please explain the relation. substrate Whereas, the levels of both the basal and << sulforaphane >>-inducible expression of [[ AKR1C1 ]] were significantly reduced in NRF2-silenced stable U937 cells compared to the control cells. Please explain the relation. indirect-upregulator In the present study, we measured the enzyme activity of thymidine kinase (TK), thymidine phosphorylase (TP) and thymidilate synthase (<< TS >>) in human cancer xenografts to investigate the contribution of these enzymes to the sensitivity of [[ TAS-102 ]]. Please explain the relation. inhibitor First, addition of apolipoprotein A-I (<< apoA-I >>), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner. Please explain the relation. product-of << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of Treatment of C57 BL/6 mice with << bleomycin >> increased fibroblast viability and collagen production and significantly downregulated [[ Nrf2 ]]. Please explain the relation. downregulator Activating << glucocorticoid receptor >>-ERK signaling pathway contributes to [[ ginsenoside Rg1 ]] protection against β-amyloid peptide-induced human endothelial cells apoptosis. Please explain the relation. activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). Please explain the relation. upregulator Using << hNET >> in transfected human embryonic kidney-293 cells, this difference in potency for DVS at sites labeled by [(3)H]NIS was found to distinguish DVS, the DVS analog rac-(1-[1-(3-chloro-phenyl)-2-(4-methylpiperazin-1-yl)-ethyl]cyclohexanol (WY-46824), [[ methylphenidate ]], and the cocaine analog 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester (RTI-55) from other hNET antagonists, such as NIS, mazindol, tricyclic antidepressants, and cocaine. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 294,"Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]."", what is the relation? downregulator Regarding the sentence ""The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure."", what is the relation? agonist Regarding the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator Regarding the sentence ""Stable ABCC1, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that << ABCC1 >> mediates the basolateral and ABCC2 the apical excretion of [[ BPDE glutathione ]] conjugates."", what is the relation? substrate Regarding the sentence ""Thus, the << NF-κB >> signaling pathway can be activated after [[ TCDD ]] treatment."", what is the relation? activator Regarding the sentence ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", what is the relation? upregulator Regarding the sentence ""Increased immunohistochemical labeling of << HIF-1alpha >>, VEGF, and BNP in the ventricular myocardium was observed in the shunt group and [[ carvedilol ]] again normalized the labeling."", what is the relation? indirect-downregulator Regarding the sentence ""<< Cobalt chloride >>, a typical HIF activator, induced the gene expression of CAR-target genes, including [[ cyp2b9 ]] and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver."", what is the relation? indirect-upregulator Regarding the sentence ""Brain but not spinal << NR2B >> receptor is responsible for the anti-allodynic effect of an NR2B subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model."", what is the relation? antagonist Regarding the sentence ""In vitro, << acetaminophen >> elicited a 4.4-fold selectivity toward COX-2 inhibition (IC(50)=113.7 micromol/L for [[ COX-1 ]]; IC(50)=25.8 micromol/L for COX-2)."", what is the relation? inhibitor Regarding the sentence ""On the other hand, the accumulation of << Ser >> through the C1-THF synthase/[[ SHMT ]] pathway in glyD plants was 2.5-fold greater than that in WT plants."", what is the relation? product-of Regarding the sentence ""Methylthioadenosine phosphorylase (<< MTAP >>) salvages purines by releasing [[ adenine ]] from methylthioadenosine and is often deleted in mesothelioma."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 295,"In reference to ""The acute toxicity of organophosphorus (OP) compounds in mammals is due to their irreversible inhibition of << acetylcholinesterase >> (AChE) in the nervous system, which leads to increased synaptic [[ acetylcholine ]] levels."", what is the relation? substrate In reference to ""Ginsenosides Rb2, Rd and Rg1 significantly decreased << norepinephrine >> and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage cell line (RAW 264.7)."", what is the relation? indirect-upregulator In reference to ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the [[ methyl CpG-binding proteins ]] (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", what is the relation? downregulator In reference to ""The most potent compound, << D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid >> (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini."", what is the relation? antagonist In reference to ""Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist salbutamol 8 mg ([[ SAL ]]), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors."", what is the relation? agonist In reference to ""Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II."", what is the relation? product-of In reference to ""In this report, we evaluated the growth-inhibitory effects of << sulindac sulfide >>, a COX-1 and [[ COX-2 ]] inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines."", what is the relation? inhibitor In reference to ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", what is the relation? agonist-activator In reference to ""<< Caerulein >> increased the levels of H(2)S and CSE mRNA expression while [[ CBS ]] mRNA expression was decreased."", what is the relation? indirect-downregulator In reference to ""In a recent study using protein-specific anti-acetyl lysine antibodies and immunological methods, we demonstrated the ability of << aspirin >> to acetylate the [[ tumor suppressor protein p53 ]]."", what is the relation? activator In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent << amino acid >> transporter, with functional features of [[ ASCT2 ]] transport."", what is the relation? upregulator In reference to ""All the compounds were evaluated for their anti-tumor activity against MCF-7, A549 and B16-F10 tumor cell lines as well as << cyclooxygenase-2 >> (COX-2)-derived [[ prostaglandin E2 ]] (PGE2) inhibitory activity of murine macrophage RAW 264.7 cell line."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 296,"The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), << nuclear factor kappa B >> (NF-κB) genes expression in [[ cisplatin ]] injected rats. what is the relation? indirect-downregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. what is the relation? agonist-activator In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport. what is the relation? upregulator The ratio between the GDC/SHMT and C1-THF synthase/<< SHMT >> pathways of [[ Ser ]] synthesis from [alpha-(13)C]Gly and [(13)C]formate, respectively, in Arabidopsis shoots was 21 : 1; in roots, 9 : 1. what is the relation? product-of One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). what is the relation? substrate_product-of Low levels of << serotonin >> may reduce the density of the [[ serotonin transporter ]] (SERT) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response"". what is the relation? downregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, [[ aspartate aminotransferase ]], alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine). what is the relation? indirect-upregulator We also observed that << fisetin >> efficiently suppressed the phosphorylation of Akt, S6K1 and [[ mTORC1 ]] in adipose tissue. what is the relation? inhibitor The potent << histamine H(1)-receptor >> antagonist cetirizine ([[ Zyrtec ]]) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine. what is the relation? antagonist Phosphorylation of ER-stress marker << eIF2α >> was also increased but only at 30 min of [[ 2-deoxyglucose ]] exposure. what is the relation? activator Cloning and characterization of a novel << human phosphodiesterase >> that hydrolyzes both [[ cAMP ]] and cGMP (PDE10A). what is the relation? substrate Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist acetylcholine ([[ ACh ]]) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump. what is the relation? agonist RESULTS: NF-kappaB/Rel activity induced by tumor necrosis factor alpha, 12-O-tetradecanoylphorbol-13-acetate, or overexpression of NF-kappaB-inducing kinase, << IKK-alpha >>, IKK-beta, or constitutively active IKK-alpha and IKK-beta mutants was inhibited dose dependently by [[ sulfasalazine ]]. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 297,"Question: What is the relation in the sentence ""Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II.""? substrate Question: What is the relation in the sentence ""<< ALD >> increased calpain expression and [[ caspase-3 ]] activity and promoted Bid cleavage.""? activator Question: What is the relation in the sentence ""<< Pranlukast >>, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from [[ leukotriene receptor ]] antagonism.""? antagonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""<< Sulindac >> metabolites and other nonsteroidal anti-inflammatory drugs selectively inhibit [[ ERK1/2 ]] phosphorylation in human colon cancer cells.""? downregulator Question: What is the relation in the sentence ""The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters ([[ alanine aminotransferase ]], aspartate aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).""? indirect-upregulator Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/[[ CIP1 ]]) and p53.""? upregulator Question: What is the relation in the sentence ""Inhibition of p95ErbB2, p185ErbB2, and EGFR phosphorylation by << GW572016 >> resulted in the inhibition of downstream phospho-Erk1/2, phospho-AKT, and [[ cyclin D ]] steady-state protein levels.""? indirect-downregulator Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""However, salicylate moiety appears to interfere with << aspirin >> inhibitory action on platelets and vascular [[ COX ]].""? inhibitor Question: What is the relation in the sentence ""The hyperglycemic effect of << m-CPBG >> central administration was blocked by pretreatment with ondansetron, a specific [[ 5-HT3 ]] receptor antagonist, indicating that the effects here obtained with m-CPBG were a result of its interaction with 5-HT3 receptors.""? agonist Question: What is the relation in the sentence ""<< GPxs >> reduce hydroperoxides to the corresponding [[ alcohols ]] by means of glutathione (GSH).""? product-of Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""Pentosan polysulfate << sodium >> (PPS) has been shown to exert antitumor activity by antagonizing the binding of [[ bFGF ]] to cell surface receptors.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 298,"Consider the text ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase ([[ CAT ]]) activity compared with the control."". Can you identify the relation? upregulator Consider the text ""Our results demonstrated that << auranofin >> suppressed [[ TLR4 ]]-mediated activation of transcription factors, NF-kappaB and IRF3, and expression of COX-2, a pro-inflammatory enzyme."". Can you identify the relation? inhibitor Consider the text ""Purified PAOh1/<< SMO >> oxidizes both spermine (K(m)=1.6 microM) and [[ N(1)-acetylspermine ]] (K(m)=51 microM), but does not oxidize spermidine."". Can you identify the relation? substrate Consider the text ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of [[ VEGF ]]and MMP-9, resulting from the inhibition of Akt pathway."". Can you identify the relation? downregulator Consider the text ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."". Can you identify the relation? agonist-activator Consider the text ""These results strongly suggest that << ABCA1 >> is substantially involved in hepatic [[ alpha-tocopherol ]] secretion."". Can you identify the relation? product-of Consider the text ""The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific)."". Can you identify the relation? agonist Consider the text ""<< Nox4 >> oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific [[ quinone ]] derivatives could modulate this activity."". Can you identify the relation? activator Consider the text ""Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and [[ mTOR ]] via suppression of Ras prenylation and enhanced Bim expression."". Can you identify the relation? indirect-downregulator Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""Although generally highly specific for << angiotensin II type 1 receptors >>, some ARBs, particularly [[ telmisartan ]], are partial agonists at peroxisome proliferator-activated receptor-γ."". Can you identify the relation? antagonist Consider the text ""The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), [[ tumor necrosis factor alpha ]] (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats."". Can you identify the relation? indirect-upregulator Consider the text ""<< Thalidomide >> has been shown to suppress [[ TNF-alpha ]] production from macrophages."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 299,"Given the text ""The << Na channel >> block caused by [[ lidocaine ]] and RSD1235 can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells."", describe the relation. inhibitor Given the text ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively."", describe the relation. upregulator Given the text ""The M564G mutated << CrAT >> showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, [[ acetyl-CoA ]]."", describe the relation. substrate Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""EP(1) and << EP(3) receptor >> antagonists [[ ONO-8713 ]] and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."", describe the relation. antagonist Given the text ""<< Zolmitriptan >> (Zomig; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura."", describe the relation. agonist Given the text ""<< HSYA >> treatment also decreased NF-κB [[ p65 ]] nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK)."", describe the relation. downregulator Given the text ""Culture of HepG2 cells with << griseofulvin >> has now been shown to induce both the formation of intracellular aggregates containing K18 as well as an increase in the abundance of [[ K18 ]] mRNA."", describe the relation. indirect-upregulator Given the text ""<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, [[ VEGF ]], GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60."", describe the relation. indirect-downregulator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", describe the relation. substrate_product-of Given the text ""We conclude that << mPGES1 >> mediates acid-induced increase in [[ PGE2 ]] production and cell proliferation."", describe the relation. product-of Given the text ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric [[ oximes ]], and BT-05 and BT-03 possessing asymmetric structure."", describe the relation. activator Given the text ""The following << TK >> blockers for treatment of various human tumors are in clinical development: Lapatinib (Lapatinib ditosylate, Tykerb, GW-572016), [[ Canertinib ]] (CI-1033), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava)."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 300,"Regarding ""Together, this pharmacological profile of subtype-selective betaAR antagonists indicates that in this model, << beta1AR >> activation is responsible for the enhanced hippocampal CA3 network activity initiated by [[ isoproterenol ]]."", can you determine the relation? agonist Regarding ""The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and [[ Aβ1-42 ]] in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of amyloid precursor protein (APP)."", can you determine the relation? indirect-upregulator Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner."", can you determine the relation? upregulator Regarding ""<< Methionine synthase reductase >> (MTRR) is an enzyme involved in the conversion of Hcy to [[ methionine ]]."", can you determine the relation? product-of Regarding ""However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]]."", can you determine the relation? activator Regarding ""These results show that << olanzapine >> eliminates [[ D2 receptor ]] priming and cognitive impairment and also alleviates decreases in neurotrophins and acetylcholinergic markers produced by D2 priming in the hippocampus."", can you determine the relation? indirect-downregulator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", can you determine the relation? agonist-activator Regarding ""The inhibitory effect of endothelin-1 on the contraction induced by 5-HT is abolished by deendothelialization, by the << endothelin ET(B) receptor >> antagonist [[ RES 701-1 ]], by indomethacin, or by glibenclamide."", can you determine the relation? antagonist Regarding ""The refolding kinetics of guanidine-denatured disulfide-intact bovine pancreatic ribonuclease A (RNase A) and its << proline-42-to-alanine >> mutant (Pro42Ala) have been studied by monitoring tyrosine burial and [[ 2'-cytidine monophosphate ]] (2'CMP) inhibitor binding."", can you determine the relation? inhibitor Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases (COX) and [[ prostaglandin E synthases ]] (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4)."", can you determine the relation? substrate Regarding ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]]."", can you determine the relation? downregulator Regarding ""<< DMI >> administration for up to 21 days produced a progressive reduction in the number of [[ 5-HT2A ]] receptors in frontal cortex, without significant alterations in occipital cortex."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 301,"Altogether, our findings support a model in which Top2β deficiency promotes << CPT >>-induced apoptosis in quiescent non-S-phase cells, possibly due to RNAP LS depletion and [[ p53 ]] accumulation. Query: What is the relation? indirect-upregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512). Query: What is the relation? upregulator PURPOSE: To compare << phenelzine >> (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase ([[ MAO ]]) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T). Query: What is the relation? inhibitor The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific). Query: What is the relation? agonist In cultured vascular smooth muscle cells (VSMCs), rAAV-mediated CYP2J2 overexpression and << EETs >> markedly suppressed Ang II-induced inflammatory [[ cytokine ]] expression. Query: What is the relation? indirect-downregulator The putative alpha 1L-adrenoceptor antagonist JTH-601, but not the << alpha 1B-adrenoceptor >> antagonist [[ chloroethylclonidine ]] (10 microM) antagonized noradrenaline-induced contractions of SMA. Query: What is the relation? antagonist Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive [[ oxygen ]] species (ROS), which are capable of initiating and promoting carcinogenesis. Query: What is the relation? product-of One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Query: What is the relation? substrate_product-of The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and [[ caspase-3 ]], and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways. Query: What is the relation? activator We conclude that Met564 blocks the entry of medium- and long-chain << acyl-CoAs >> to the catalytic site of [[ CrAT ]]. Query: What is the relation? substrate The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against [[ COX-2 ]] (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM). Query: What is the relation? downregulator Here, we characterized the target profile of the dual << SRC >>/ABL inhibitor [[ bosutinib ]] employing a two-tiered approach using chemical proteomics to identify natural binders in whole cell lysates of primary CML and K562 cells in parallel to in vitro kinase assays against a large recombinant kinase panel. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 302,"Question: What is the relation in the sentence ""Among the [Fe-S] cluster biosynthetic proteins are included a pyridoxal phosphate-dependent enzyme (<< NifS >>) that is involved in the activation of sulphur from [[ l-cysteine ]], and a molecular scaffold protein (NifU) upon which [Fe-S] cluster precursors are formed.""? substrate Question: What is the relation in the sentence ""Inhibition by << phenformin >> of oxygen consumption via [[ complex I ]] respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of phenformin on complex I respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts.""? inhibitor Question: What is the relation in the sentence ""3. << CYP3A >> induction in the liver increased depending on the dose of DEX-P, whereas that in intestine showed a mild increase, but the induction level was almost constant regardless of the dose of [[ DEX-P ]].""? activator Question: What is the relation in the sentence ""In Alexander cells, only when they were transfected with FXR+RXR, << GW4064 >> caused up-regulation of SHP and OSTβ, and a down-regulation of [[ CYP27A1 ]].""? indirect-downregulator Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""The inhibition of UG synthesis and << PR >> down-regulation by [[ 5 alpha-NET ]] and 3 beta,5 alpha-NET indicates that these NET metabolites possess antiprogestational properties.""? indirect-upregulator Question: What is the relation in the sentence ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h.""? upregulator Question: What is the relation in the sentence ""<< Uridine 5'-diphosphate- glucuronosyltransferases >> are colocalized with carboxylesterases and have the potential to further metabolize carboxylic acids to [[ acyl glucuronides ]], but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases.""? product-of Question: What is the relation in the sentence ""The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific).""? agonist Question: What is the relation in the sentence ""The << 5-HT(2B/2C)-receptor >> antagonist [[ SB 206553 ]] facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect.""? antagonist Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]].""? agonist-activator Question: What is the relation in the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""Expression of the dominant negative mutants arrestin-2(319-418) or dynamin I-K44A significantly reduced << U50,488H >>-induced down-regulation of the [[ hkor ]].""? downregulator Question: What is the relation in the sentence ""Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (<< OSI-774 >>, Tarceva) and Sunitinib (SU 11248, Sutent) specific for [[ VEGF receptor ]] kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 303,"Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, IL-27 mRNA, TLR4 protein, NF-κB p65 protein, and [[ IL-27 ]] p28 protein (p < 0.05). Question: what is the relation? Answer: indirect-downregulator In combination with clofarabine, the ability of << resveratrol >> to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment. Question: what is the relation? Answer: downregulator Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both << cAMP >> and cGMP ([[ PDE10A ]]). Question: what is the relation? Answer: substrate Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor The non-selective adenosine receptor antagonist (caffeine), and the selective << adenosine A1 receptor >> antagonist ([[ DPCPX ]]), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice. Question: what is the relation? Answer: antagonist Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity. Question: what is the relation? Answer: upregulator << Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce carboxylic acids and resulting alcohols, [[ amines ]], and thiols, respectively. Question: what is the relation? Answer: product-of The concentration response to << levcromakalim >> (LEVC), a [[ K(ATP) channel ]] opener, was significantly shifted to the left in the inflamed smooth-muscle cells. Question: what is the relation? Answer: activator The selective << beta1AR >> antagonists atenolol and metoprolol blocked [[ isoproterenol ]]-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively. Question: what is the relation? Answer: agonist To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, << sodium hydrosulphide >> (NaHS), (10, 50 and 100 muM), that resulted in a significant increase in [[ SP ]] concentration and expression of PPT-A and NK1-R in acinar cells. Question: what is the relation? Answer: indirect-upregulator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of << Pyrrolidine dithiocarbamate >> (PDTC), a specific [[ NF-κB ]] inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity. Question: what is the relation? Answer: inhibitor RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Question: what is the relation? Answer: agonist-activator << Olopatadine >> is a selective [[ histamine H1-receptor ]] antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 304,"Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."", what is the relation? upregulator Regarding the sentence ""<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate ([[ PMA ]]) in WEHI-231, HOP-92, and Colo-205 cells."", what is the relation? downregulator Regarding the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator Regarding the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor Regarding the sentence ""The << CYP2B6*6 >> allele is associated with reduced enzyme expression and activity that may lead to interindividual variability in [[ ketamine ]] metabolism."", what is the relation? substrate Regarding the sentence ""In membranes from HEK293 cells transfected with << alpha2-receptors >>, etomidate inhibited binding of the alpha2-antagonist, [[ [3H]RX821002 ]], with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm)."", what is the relation? antagonist Regarding the sentence ""A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the VEGFR << tyrosine kinase >> inhibitors sunitinib and/or [[ sorafenib ]]."", what is the relation? inhibitor Regarding the sentence ""The identification of the succinate receptor << SUCNR1 >> in platelets is of particular interest, because physiologically relevant concentrations of [[ succinate ]] were shown to potentiate the effect of low doses of a variety of platelet agonists."", what is the relation? agonist Regarding the sentence ""These results indicate transcription of << FDX1 >> is regulated by the NR5A family and cAMP signaling, and participates in [[ steroid ]] hormone production in ovarian granulosa cells."", what is the relation? product-of Regarding the sentence ""Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of << p21 >>(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2."", what is the relation? indirect-upregulator Regarding the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal << cytochrome P450 3A >> (CYP3A) in rats using dexamethasone 21-phosphate ([[ DEX-P ]]) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively."", what is the relation? activator Regarding the sentence ""Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (<< 1400W >>), a selective inhibitor of iNOS, decreased the expression of [[ E-selectin ]], VEGF, and iNOS."", what is the relation? indirect-downregulator Regarding the sentence ""Additionally, these effects of << ATO >> on γ-H2AX, Chk1, Chk2, [[ p53 ]], and p21(waf1/cip1) were reduced by an ATM inhibitor."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 305,"Regarding the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using dexamethasone 21-phosphate (DEX-P) and [[ midazolam ]] (MDZ) as an inducer and a substrate to CYP3A, respectively."", what is the relation? substrate Regarding the sentence ""These results indicate that, similar to the sulfonylureas, mitiglinide is highly specific to the Kir6.2/SUR1 complex, i.e., the pancreatic beta-cell << K(ATP) channel >>, and suggest that [[ mitiglinide ]] may be a clinically useful anti-diabetic drug."", what is the relation? agonist Regarding the sentence ""Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (<< BLT-4 >>), blocked [[ ABCA1 ]]-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM)."", what is the relation? inhibitor Regarding the sentence ""The data indicated that << PhIP >> could cause stomach injury, oxidative stress in rat stomachs as well as the activation of [[ c-fos ]] and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer."", what is the relation? activator Regarding the sentence ""The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists terfenadine, astemizole, [[ loratadine ]], and acrivastine are reviewed."", what is the relation? antagonist Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""In addition to CYP2B6, << anisomycin >> co-treatment potentiated an increase in CYP2A7 and [[ CYP2C9 ]] mRNAs but not CYP3A4 or UDP-glucuronosyltransferase 1A1 mRNAs."", what is the relation? indirect-upregulator Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory [[ cytokines ]], increased adiponectin expression and improved glucose tolerance parallel to insulin sensitivity in obese mice."", what is the relation? indirect-downregulator Regarding the sentence ""Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats."", what is the relation? upregulator Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""<< Crocin >> (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of [[ cytochrome c ]] to the cytosol induced by DZN."", what is the relation? downregulator Regarding the sentence ""The latter reaction, catalyzed by << aspartoacylase >> (ASPA), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter."", what is the relation? product-of Regarding the sentence ""Lymphocytes possess the essential components of a cholinergic system, including << acetylcholine >> (ACh); choline acetyltransferase ([[ ChAT ]]), its synthesizing enzyme; and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 306,"BACKGROUND: Since the introduction of the first << cholinesterase >> inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, [[ galantamine ]] and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase. Query: What is the relation? inhibitor Also in contrast to effects of multiple << METH >> injections, 1) MDMA caused little or no decrease in binding of the [[ DAT ]] ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal DA transport. Query: What is the relation? downregulator Independent of dietary choline, supplemental << Met >> increased hepatic [[ BHMT ]] activity approximately 30%. Query: What is the relation? activator Expression of << L-type pyruvate kinase >> (L-PK) is upregulated in the liver by dietary [[ carbohydrate ]]. Query: What is the relation? indirect-upregulator In contrast, the selective << beta2AR >> antagonists ICI-118,551 and butoxamine inhibited [[ isoproterenol ]]-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively). Query: What is the relation? agonist Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system. Query: What is the relation? product-of Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Query: What is the relation? agonist-activator Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, [[ survivin ]], cyclin D1, MMP7, and c-Myc. Query: What is the relation? indirect-downregulator Then the cells were treated with various concentrations of apoE3, lactoferrin and bovine serum albumin with or without 100 microg/ml of GMC, and the << SGLT1 >>-dependent methyl alpha-D-glucopyranoside ([[ AMG ]]) uptake and levels of SGLT1 expression were determined. Query: What is the relation? substrate The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists << SB224289 >> (300 microg/kg; [[ 5-HT1B ]]), BRL15572 (300 microg/kg; 5-HT1D), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C). Query: What is the relation? antagonist Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). Query: What is the relation? upregulator Furthermore, the enzymatic activity of alanine aminotransferase (<< ALT >>), which converts the critical gluconeogenic [[ amino acid ]] alanine into pyruvate, is decreased (approximately 50%) in KLF15-/- hepatocytes. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 307,"Question: What is the relation in the sentence ""The latter reaction, catalyzed by aspartoacylase (<< ASPA >>), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter.""? product-of Question: What is the relation in the sentence ""Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512).""? upregulator Question: What is the relation in the sentence ""Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and [[ AM4054 ]] [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.""? agonist Question: What is the relation in the sentence ""Cytotoxicity assays demonstrated that epigallocatechin 3-O-gallate (<< EGCG >>) and most of compounds 1-6 killed preferentially [[ OATP ]]-expressing CHO cells.""? substrate Question: What is the relation in the sentence ""Separate 5-aza-2'-deoxycytidine pretreatment or in combination with << trichostatin A >> reduced (m)CpG and specific small interference RNAs targeting Mecp2 and [[ Creb1 ]] separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.""? indirect-downregulator Question: What is the relation in the sentence ""Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while << TDCPP >> induced [[ CYP3A37 ]] and CYP2H1.""? indirect-upregulator Question: What is the relation in the sentence ""They included the COX-1 inhibitor indomethacin; the COX-2 inhibitor NS-398; the mixed COX-1/COX-2 inhibitor ibuprofen; the nitric oxide (NO) derivatives of indomethacin, ibuprofen and flurbiprofen; the 5-LOX inhibitor REV 5901; and the 5-LOX activating protein (<< FLAP >>) inhibitor [[ MK-886 ]].""? inhibitor Question: What is the relation in the sentence ""Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of << inducible nitric-oxide synthase >> by [[ 15-deoxy-Delta12,14-prostaglandin J2 ]].""? downregulator Question: What is the relation in the sentence ""<< (+/-)-Tamsulosin >>, over the range of concentrations at which it antagonized the positive inotropic effect mediated by [[ alpha 1-adrenoceptors ]], did not affect the accumulation of [3H]inositol phosphates that was induced by 10 microM phenylephrine.""? antagonist Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""In addition, PSE inhibited the transcriptional activity of NFAT without interfering with the << calcium >>-induced [[ NFAT ]] dephosphorylation event, which represents the major signaling pathway for its activation.""? activator Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Among the various enzymes, << dicoumarol >> inhibitable cytosolic NAD(P)H:quinone oxidoreductase1 ([[ NQO1 ]]) was shown to catalyse bioreductive activation of MMC leading to cross-linking of the DNA and cytotoxicity.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 308,"Regarding the sentence ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, cinnamic aldehyde, and [[ hydrogen peroxide ]]) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."", what is the relation? activator Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."", what is the relation? upregulator Regarding the sentence ""Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect of an << NR2B >> subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model."", what is the relation? antagonist Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist salbutamol 8 mg ([[ SAL ]]), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors."", what is the relation? agonist Regarding the sentence ""A novel << benzo[d]imidazole >> derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of [[ NLRP3 ]] inflammasome."", what is the relation? inhibitor Regarding the sentence ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system."", what is the relation? product-of Regarding the sentence ""RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than [[ COX-1 ]] (IC(50) = 0.210 microM)."", what is the relation? downregulator Regarding the sentence ""<< Phenytoin >> is principally metabolized by CYP2C9, and both are probable substrates of the drug transporter [[ P-glycoprotein ]]."", what is the relation? substrate Regarding the sentence ""Nox4 << oxidase >> activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific [[ quinone ]] derivatives could modulate this activity."", what is the relation? indirect-upregulator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Repression of << HDC >> gene expression and HDC activity by [[ dexamethasone ]] may underlie its therapeutic effect in the treatment of allergy."", what is the relation? indirect-downregulator Regarding the sentence ""Both fatty acids, but << DHA >> to a lesser extent compared with EPA, selectively and dose-dependently reduced the percentage of [[ cytokine ]]-expressing Th cells in a peroxisome proliferator-activated receptor (PPAR)γ-dependent fashion, whereas the expression of the cell surface marker CD69 was unaltered on activated T cells."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 309,"<< Cycloxygenase-2 >> (COX-2)-derived prostaglandin E2 ([[ PGE2 ]]) has been shown to be important in esophageal tumorigenesis. what is the relation? product-of The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by << Tomudex >> indicate that increased [[ cyclin E ]]-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance. what is the relation? indirect-upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. what is the relation? agonist-activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (<< Pin1 >>), an enzyme that catalyzes the conversion of the peptide bond of [[ pSer ]]/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification. what is the relation? substrate The selective << beta1AR >> antagonists atenolol and [[ metoprolol ]] blocked isoproterenol-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively. what is the relation? antagonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). what is the relation? substrate_product-of However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]]. what is the relation? activator Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist [[ formoterol ]] [eformoterol]. what is the relation? agonist << DEX >> enhanced the ratio [[ IFN-gamma ]]/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). what is the relation? upregulator Low levels of << serotonin >> may reduce the density of the [[ serotonin transporter ]] (SERT) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response"". what is the relation? downregulator Inhibition of << human iNOS promoter >>-driven luciferase activity by [[ gemfibrozil ]] in cytokine-stimulated U373MG astroglial cells suggests that this compound inhibits the transcription of iNOS. what is the relation? inhibitor Inhibition of endogenous production of << H(2)S >> by PAG significantly suppressed SP concentration, [[ PPT-A ]] expression and NK1-R expression in the acini. what is the relation? indirect-downregulator One group of experimental animals was treated with << 5-lipoxygenase >> (5-LO) inhibitor, diethylcarbamazine ([[ DEC ]], Sigma, St. Louis, Missouri) (50 mg/kg, i.v.), immediately before blast. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 310,"Question: What is the relation in the sentence ""<< Sorafenib >> inhibited the [[ kinase ]] activity of both C-RAF and B-RAF (wild type and V600E mutant).""? inhibitor Question: What is the relation in the sentence ""The positive correlation between vitamin A and immunoglobulin A concentrations might be the result of the << vitamin A >> inductive effect during [[ immunoglobulins A ]] synthesis.""? upregulator Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma.""? agonist-activator Question: What is the relation in the sentence ""There was no significant difference in << TLR4 >>, NF-κB, and IL-27 mRNA and proteins between [[ curcumin ]]-treated and sulfasalazine-treated groups.""? indirect-downregulator Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""The primary aim of these studies was to test the hypothesis that << HSD11B1 >>-derived [[ cortisol ]] has a biological role in endometrial function and conceptus development during early pregnancy in sheep.""? product-of Question: What is the relation in the sentence ""SIRT1 co-precipitated with PPARα and << nicotinamide >> increased the acetylation of the PPARα coactivator [[ PGC-1α ]], which was suppressed by resveratrol.""? activator Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the [[ incretin hormones ]] glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.""? indirect-upregulator Question: What is the relation in the sentence ""Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo.""? substrate Question: What is the relation in the sentence ""Also consistent with the involvement of Gq coupled EP1 receptors, the PGE1 stimulation is inhibited by the PKCI vector (encoding the PKC inhibitory domain), the PKC inhibitor Go 6976, thapsigargin, as well as the << calmodulin >> antagonists W7 and [[ W13 ]].""? antagonist Question: What is the relation in the sentence ""While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of [[ H1-receptor ]] antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity.""? agonist Question: What is the relation in the sentence ""At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of GluN1/[[ GluN2B ]] receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic.""? downregulator Question: What is the relation in the sentence ""In cell culture experiments, it was found that << triclosan >> inhibited [[ IL-1 beta ]] induced prostaglandin E2 production by human gingival fibroblasts in a concentration dependent manner, and at relatively low concentrations.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 311,"In reference to ""<< Sulindac >> metabolites and other nonsteroidal anti-inflammatory drugs selectively inhibit [[ ERK1/2 ]] phosphorylation in human colon cancer cells."", what is the relation? downregulator In reference to ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", what is the relation? agonist-activator In reference to ""METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of << [(3)H] dopamine >> (DA) uptake and [(3)H]WIN 35428 binding in human dopamine transporter ([[ DAT ]]) wild-type and mutants with altered conformational equilibria."", what is the relation? substrate In reference to ""In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with rauwolscine, phentolamine, and [[ idazoxan ]]."", what is the relation? antagonist In reference to ""Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal NGF, BDNF and [[ ChAT ]] that was eliminated by olanzapine treatment."", what is the relation? indirect-downregulator In reference to ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", what is the relation? substrate_product-of In reference to ""Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."", what is the relation? upregulator In reference to ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of << caspase 3 >> and release of cytochrome c to the cytosol induced by [[ DZN ]]."", what is the relation? activator In reference to ""RGM-1 cells were treated with CDCA or << GW4064 >>, an [[ FXR ]] agonist, in the presence or absence of guggulsterone, an FXR antagonist."", what is the relation? agonist In reference to ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of << cytochrome c >> to the cytosol induced by [[ DZN ]]."", what is the relation? indirect-upregulator In reference to ""Acetylcholinesterase (<< AChE >>) inhibited by the organophosphate soman ([[ 1,2,2-trimethyl-propylmethylphosphonofluoridate ]]) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex."", what is the relation? inhibitor In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""Rats were fed experimental diets containing SPI or << casein >> as a [[ nitrogen ]] source."", what is the relation? product-of In reference to ""Interestingly, << Acrolein >> increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter [[ receptor for advanced glycation end products ]], and decreased A-disintegrin and metalloprotease (ADAM) 10 levels."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 312,"Regarding the sentence ""The significantly decreased levels of << p-PI3K >> and p-AKT expression were observed in SGC-7901 cells after [[ β-ionone ]] treatments in a time- and dose-dependent manner (P < 0.01)."", what is the relation? indirect-downregulator Regarding the sentence ""High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates [[ tuberin ]] and activates mTOR."", what is the relation? downregulator Regarding the sentence ""Licofelone almost abolished << 5-LOX >> activity by inhibiting [[ leukotriene B4 ]] generation in rabbit neutrophils and prevented platelet thromboxane B2 production from whole blood."", what is the relation? product-of Regarding the sentence ""<< CCl(4) >> administration triggered inflammatory response in mice livers by activating [[ nuclear factor-kappaB ]] (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2)."", what is the relation? activator Regarding the sentence ""<< Alprenolol >> and bromoacetylalprenololmenthane are competitive slowly reversible antagonists at the [[ beta 1-adrenoceptors ]] of rat left atria."", what is the relation? antagonist Regarding the sentence ""<< Bupropion >>, an efficacious antidepressant and smoking cessation agent, inhibits dopamine and norepinephrine transporters ([[ DAT ]] and NET, respectively)."", what is the relation? inhibitor Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin-A, PPT-A) and neurokinin-1 receptor (<< NK-1R >>), the primary receptor for SP, are increased in secretagogue [[ caerulein ]]-treated acinar cells."", what is the relation? indirect-upregulator Regarding the sentence ""The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the << adenosine A3 receptor >> agonist [[ IB-MECA ]] (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0.75 mg/kg b.w."", what is the relation? agonist Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Of the << PDE >> inhibitors tested, dipyridamole was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of [[ cAMP ]] and cGMP hydrolysis, respectively."", what is the relation? substrate Regarding the sentence ""CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", what is the relation? upregulator Regarding the sentence ""In the present studies, the << CB(1) >> inverse agonist [[ SR141716A ]] (rimonabant) and the CB(1) neutral antagonist AM4113 were compared for their ability to modify CB(1) receptor-mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB(1) full agonist AM4054."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",12,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist-inhibitor 313,"Regarding ""Specifically, << all-trans-13,14-dihydroretinol >> is transiently oxidized to all-trans-13,14-dihydroretinoic acid before being oxidized further by [[ Cyp26 ]] enzymes."", can you determine the relation? substrate Regarding ""These results suggest that << ACS1 >> and ACS4 may be linked to [[ triacylglycerol ]] synthesis."", can you determine the relation? product-of Regarding ""The concentration response to << levcromakalim >> (LEVC), a [[ K(ATP) channel ]] opener, was significantly shifted to the left in the inflamed smooth-muscle cells."", can you determine the relation? activator Regarding ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", can you determine the relation? agonist-activator Regarding ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""Cotreatment with U0126 and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of << sulindac >> treatment on ERK1/2, JNK, and [[ beta-catenin ]]."", can you determine the relation? indirect-downregulator Regarding ""Activating glucocorticoid receptor-ERK signaling pathway contributes to << ginsenoside Rg1 >> protection against [[ β-amyloid peptide ]]-induced human endothelial cells apoptosis."", can you determine the relation? inhibitor Regarding ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."", can you determine the relation? upregulator Regarding ""This effect has been attributed to the antagonist effects of << pindolol >> at the [[ 5-HT(1A) ]] receptor."", can you determine the relation? antagonist Regarding ""<< OMT >> showed partial protection in the cortical neurons via down-regulation of NR2B containing [[ NMDA receptors ]] and up-regulation of Bcl-2 family."", can you determine the relation? downregulator Regarding ""Furthermore, treatment with spironoclactone not only attenuated the pro-apoptotic effect of ALD but reversed the << ALD >>-induced increase of [[ calpain ]] and AIF levels."", can you determine the relation? indirect-upregulator Regarding ""The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the << adenosine A3 receptor >> agonist [[ IB-MECA ]] (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0.75 mg/kg b.w."", can you determine the relation? agonist Regarding ""The Schild plots for the competitive antagonists WB4101 and 5-methyl-urapidil against << alpha 1a-adrenoceptor >>-selective agonist methoxamine-induced contraction were linear and had slopes not significantly different from unity, with a pA2 of 9.07 +/- 0.07 (n = 5) for WB4101 and 9.09 +/- 0.05 (n = 3) for [[ 5-methyl-urapidil ]]."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 314,"Consider the text ""Treatment with << diclofenac >> resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated [[ caspase-3 ]] after 6 hr, indicating that diclofenac may cause apoptosis of neuronal cells via activation of the caspase cascade."". Can you identify the relation? activator Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."". Can you identify the relation? agonist-activator Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Conversely, opioid antagonists such as << naloxone >> and naltrexone (which bind to non-selectively [[ opioid receptors ]]) have been shown to decrease alcohol consumption under various experimental conditions."". Can you identify the relation? antagonist Consider the text ""We conclude that Met564 blocks the entry of medium- and long-chain << acyl-CoAs >> to the catalytic site of [[ CrAT ]]."". Can you identify the relation? substrate Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase ([[ CAT ]]) activity compared with the control."". Can you identify the relation? upregulator Consider the text ""Prazosin (nonselective << alpha(1)-adrenoceptor >> antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively)."". Can you identify the relation? agonist Consider the text ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."". Can you identify the relation? downregulator Consider the text ""Effects of inhibition of << urokinase-type plasminogen activator >> (u-PA) by [[ amiloride ]] in the cornea and tear fluid of eyes irradiated with UVB."". Can you identify the relation? inhibitor Consider the text ""<< HSYA >> suppressed the expression of TLR-4, [[ Myd88 ]], ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells."". Can you identify the relation? indirect-downregulator Consider the text ""<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS)."". Can you identify the relation? product-of Consider the text ""Although Bak and Bcl-2-associated X protein (Bax), another member of the Bcl-2 family, are generally thought to be functionally redundant, only Bak is necessary and sufficient for << VK2 >>-induced [[ cytochrome c ]] (cyt c) release and cell death."". Can you identify the relation? indirect-upregulator Consider the text ""Given the treatment with three doses of << Captopril >> (15 approximately 45 mg/kg) markedly attenuated inhibition of vasodilator responses to ACh, and eliminated the increased level of malondialdehyde, the decreased level of NO, activity of [[ PON1 ]] and SOD in serum by single intragastric gavaged L-methionine."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 315,"The enzyme << dimethylarginine dimethylaminohydrolase >> (DDAH) specifically hydrolyzes these asymmetrically methylated [[ arginine ]] residues to citrulline and methylamines. Query: What is the relation? substrate << Thalidomide >> reduced [[ COX-2 ]] expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60. Query: What is the relation? indirect-downregulator Among these differentially expressed lncRNAs, the greatest change was noted for << uc002mbe.2 >>, which had more than 300 folds induction upon [[ TSA ]] treatment. Query: What is the relation? indirect-upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. Query: What is the relation? upregulator Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as GluN1/GluN2B [[ N-Methyl-D-aspartate Receptor ]] Antagonists. Query: What is the relation? antagonist << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, [[ c-Myc ]], and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Query: What is the relation? downregulator The identification of the << succinate receptor >> SUCNR1 in platelets is of particular interest, because physiologically relevant concentrations of [[ succinate ]] were shown to potentiate the effect of low doses of a variety of platelet agonists. Query: What is the relation? agonist Synthesis and antitumor activity of 1,3,4-oxadiazole possessing << 1,4-benzodioxan >> moiety as a novel class of potent [[ methionine aminopeptidase type II ]] inhibitors. Query: What is the relation? inhibitor Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected << rat D2 dopamine receptors >> (rD2(long)) by [[ quinpirole ]] had no effect. Query: What is the relation? activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Query: What is the relation? agonist-activator Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS. Query: What is the relation? product-of OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of nebulized arformoterol tartrate (a selective, long-acting << beta(2)-adrenergic >> agonist that is the [[ [R,R] isomer of formoterol ]]) and salmeterol xinafoate versus placebo in patients with chronic obstructive pulmonary disease (COPD). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 316,"It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of [[ I-κBε ]] and nuclear translocation of c-Rel/p50 in alveolar epithelial cells. Question: what is the relation? Answer: downregulator << EROD >> activity induction in peripheral blood lymphocytes, liver and brain tissues of rats orally exposed to [[ polycyclic aromatic hydrocarbons ]]. Question: what is the relation? Answer: activator Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 ([[ hCES1 ]]) and 2 (hCES2). Question: what is the relation? Answer: substrate Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of Results: The administration of << prallethrin >> 1.6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, hemoglobin, packed cell volume, platelets, mean corpuscular volume, and mean corpuscular [[ hemoglobin ]] in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h. Question: what is the relation? Answer: indirect-upregulator Zolmitriptan (<< Zomig >>; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura. Question: what is the relation? Answer: agonist Coagulation-induced << thromboxane B(2) >> and lipopolysaccharide-induced prostaglandin E(2) were measured ex vivo and in vitro in human whole blood as indices of [[ COX-1 ]] and COX-2 activity. Question: what is the relation? Answer: product-of Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats. Question: what is the relation? Answer: upregulator << Sumatriptan >> and LY 344864 decreased the number of capsaicin-induced [[ c-fos ]]-like immunoreactive cells within trigeminal nucleus caudalis (ID50 = 0.04 and 0.6 mg kg(-1)). Question: what is the relation? Answer: indirect-downregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Question: what is the relation? Answer: agonist-activator Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of [[ propranolol ]]>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>atenolol. Question: what is the relation? Answer: antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor [-]-Huperzine A (<< [-]-Hup A >>), is a naturally occurring potent reversible [[ AChE ]] inhibitor that penetrates the blood-brain barrier. Question: what is the relation? Answer: inhibitor Sorafenib and << sunitinib >> are synthetic, orally active agents shown to directly inhibit vascular endothelial growth factor receptors -2 and -3 ([[ VEGFR-2 ]], VEGFR-3) and platelet-derived growth factor receptor beta (PDGFR-beta), while temsirolimus is an mTOR inhibitor. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 317,"CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of [[ HDC ]] gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity. Please explain the relation. product-of << All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]]. Please explain the relation. upregulator Block of human NaV1.5 << sodium channels >>[[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin. Please explain the relation. substrate The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Please explain the relation. agonist-activator The potent << histamine H(1)-receptor >> antagonist [[ cetirizine ]] (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine. Please explain the relation. antagonist Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of << Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase ([[ PI3K ]])/Akt/ glycogen synthase kinase 3β (GSK-3β) signaling pathway. Please explain the relation. indirect-downregulator Moreover, recent in vitro studies suggest that << memantine >> abrogates [[ beta-amyloid ]] (Abeta) toxicity and possibly inhibits Abeta production. Please explain the relation. downregulator Combined treatment of << Mn >> and DA further augments cell toxicity, ROS production and [[ JNK ]] phosphorylation in LRRK2 deficient cells compared to controls. Please explain the relation. activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor << manumycin A >> caused elevation of [[ ApoA-I ]] secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. Please explain the relation. indirect-upregulator We have examined the effects of the synthetic matrix metalloproteinase inhibitor, batimastat (BB-94) and the << angiotensin-converting enzyme >> inhibitor, [[ captopril ]], on metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice. Please explain the relation. inhibitor These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and << oxymetazoline >>-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates. Please explain the relation. agonist METHODS: The effect of leukotriene D(4) and the << leukotriene receptor >> antagonist, pranlukast hydrate ([[ ONO-1078 ]]) on the regulation of MUC2/5AC gene expression and mucin secretion were observed in human airway NCI-H292 epithelial cells. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 318,"Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor The use of << A3 receptor >> agonist [[ IB-MECA ]] attenuates EAP. Question: what is the relation? Answer: agonist In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of << AMP >> to adenosine by [[ ecto-5'-nucleotidase ]]. Question: what is the relation? Answer: substrate << I3A >> induced a higher level of secretion of the inflammatory cytokine [[ interleukin 6 ]] compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction. Question: what is the relation? Answer: indirect-upregulator Pretreatment of the splenocytes with both BPB and << AACOCF3 >> suppressed phorbol 12-myristate 13-acetate plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner. Question: what is the relation? Answer: indirect-downregulator The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). Question: what is the relation? Answer: downregulator The << COX >> pathway generates inflammatory [[ prostaglandins ]], while the 5-LOX pathway generates inflammatory leukotrienes. Question: what is the relation? Answer: product-of One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Lastly, we found that << RhoA >> activation by [[ cucurbitacin I ]] is mediated by reactive oxygen species (ROS). Question: what is the relation? Answer: activator EP(1) and << EP(3) receptor >> antagonists ONO-8713 and [[ ONO-AE3-240 ]], but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth. Question: what is the relation? Answer: antagonist The kinase activity of << EGFR >> was little inhibited by [[ TT-B ]] in a cell-free system. Question: what is the relation? Answer: inhibitor Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). Question: what is the relation? Answer: upregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Question: what is the relation? Answer: agonist-activator Various genes controlled by << estrogen >>, including X-inactive-specific transcript, anterior gradient-2, [[ trefoil factor-1 ]], CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 319,"Regarding the sentence ""Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM [[ 2,3,7,8-tetrachlorodibenzodioxin ]] (TCDD), the most potent activator of AhR."", what is the relation? indirect-upregulator Regarding the sentence ""Risperidone is metabolized to its active metabolite, << 9-hydroxyrisperidone >>, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4."", what is the relation? product-of Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Unlike the sedative hypnotics that target GABA(A) receptor complexes, << ramelteon >> is a chronohypnotic that acts on the melatonin [[ MT(1) ]] and MT(2) receptors, which are primarily located in the suprachiasmatic nucleus, the body's ""master clock."" As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades."", what is the relation? agonist Regarding the sentence ""The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (lorglumide, << CR 1409 >>), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini."", what is the relation? antagonist Regarding the sentence ""In addition, << 5HHMF >> blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and [[ p50 ]], which are important molecules involved in the regulation of iNOS expression."", what is the relation? indirect-downregulator Regarding the sentence ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, [[ tert-butylhydroquinone ]], cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."", what is the relation? activator Regarding the sentence ""Suppression of << Src >>/ERK and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells."", what is the relation? downregulator Regarding the sentence ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport."", what is the relation? upregulator Regarding the sentence ""Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas << ursolic acid >> attenuated the phosphorylation of [[ AKT ]] and mTOR in HepG2 cells."", what is the relation? inhibitor Regarding the sentence ""Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, estrone 3-sulfate, and << dehydroepiandrosterone sulfate >> (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either [[ OATP1B1 ]] or OATP1B3."", what is the relation? substrate Regarding the sentence ""Several effects of << polyphenols >> are useful in this scenario, including a reduction in the activities of cytokines and modulation of cellular metabolism through [[ histone deacetylase ]] inhibitors, AMPK activators, calorie-restriction mimetics or epigenetic regulators."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 320,"The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity. Please explain the relation. upregulator << Thymidine kinase-1 >> (TK-1) and thymidylate synthase (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively. Please explain the relation. product-of Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of CA I and [[ CA II ]]. Please explain the relation. downregulator Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and << BMY-7378 >> (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective [[ alpha(1D)-adrenoceptor ]] antagonist) competitively antagonized the phenylephrine-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively). Please explain the relation. antagonist In further studies, the diuretic effects of the << CB1 >> agonist [[ AM4054 ]] were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]. Please explain the relation. agonist Here we studied the effects of the recently developed << monoacylglycerol lipase >> inhibitor [[ JZL184 ]] on basal and stress-induced corticosterone levels in male CD1 mice, and found that this compound dramatically increased basal levels without affecting stress responses. Please explain the relation. inhibitor Both risperidone and << 9-hydroxyrisperidone >> are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination. Please explain the relation. substrate Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]]. Please explain the relation. activator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of In conclusion, the production of << IL-4 >> and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by [[ DEX ]] than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma. Please explain the relation. indirect-downregulator Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal NGF, BDNF and << ChAT >> that was eliminated by [[ olanzapine ]] treatment. Please explain the relation. indirect-upregulator Inhibition of the NF-kappaB pathway was responsible for this effect since the << colchicoside >> inhibited RANKL-induced NF-kappaB activation, activation of IkappaB kinase (IKK) and suppressed inhibitor of [[ NF-kappaBalpha ]] (IkappaBalpha) phosphorylation and degradation, an inhibitor of NF-kappaB. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 321,"In reference to ""To investigate the possibility that felbamate's favorable toxicity profile could be related to NMDA receptor subtype selectivity, we examined the specificity of << felbamate >> block of recombinant NMDA receptors composed of the NR1a subunit and various [[ NR2 ]] subunits."", what is the relation? inhibitor In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""Compared with DM8W group, << SOD >> and ALDH2 in [[ EtOH ]]+DM8W group was increased, MDA was decreased."", what is the relation? indirect-upregulator In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), [[ CDK4 ]], c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator In reference to ""Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately [[ levobetaxolol ]]>levobunolol approximately carteolol>/=timolol>atenolol."", what is the relation? antagonist In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""<< GPxs >> reduce hydroperoxides to the corresponding [[ alcohols ]] by means of glutathione (GSH)."", what is the relation? product-of In reference to ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", what is the relation? upregulator In reference to ""Absorption and secretion of << fluoride >> increase at acid pH levels, possibly because of its non-ionized state at these pHs and/or because of participation of a F(-)/H(+) cotransporter or a [[ F(-)/OH(-) antiporter ]]."", what is the relation? substrate In reference to ""To explore the molecular basis for CPT hypersensitivity in Top2β-deficient cells, we found that upon << CPT >> exposure, the RNA polymerase II large subunit (RNAP LS) became progressively depleted, followed by recovery to nearly the original level in wild-type MEFs, whereas [[ RNAP LS ]] remained depleted without recovery in Top2β-deficient cells."", what is the relation? indirect-downregulator In reference to ""Unlike the sedative hypnotics that target GABA(A) receptor complexes, << ramelteon >> is a chronohypnotic that acts on the melatonin MT(1) and [[ MT(2) ]] receptors, which are primarily located in the suprachiasmatic nucleus, the body's ""master clock."" As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades."", what is the relation? agonist In reference to ""Activating << glucocorticoid receptor >>-ERK signaling pathway contributes to [[ ginsenoside Rg1 ]] protection against β-amyloid peptide-induced human endothelial cells apoptosis."", what is the relation? activator In reference to ""Exposure of freshly isolated subcutaneous and omental adipocytes in suspension culture to << troglitazone >> induced a similar reduction of [[ PAI-1 ]] concentration in the culture medium (by 35 +/- 11%, p < 0.05, and 33 +/- 8%, p < 0.05 compared with control, respectively)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 322,"Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, IL-18, IL-17A and << IFN-γ >>, were markedly suppressed by [[ Fc11a-2 ]]. Query: What is the relation? indirect-downregulator OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of << FADS2 >> affects the [[ PUFA ]] biosynthetic pathway and consequently modifies the effect of alpha-linolenic acid (ALA) on myocardial infarction (MI). Query: What is the relation? product-of Mammalian ALDH1B1, another mitochondrial enzyme sharing 72% identity with << ALDH2 >>, is also capable of metabolizing [[ acetaldehyde ]] but has a tissue distribution and pattern of activity distinct from that of ALDH2. Query: What is the relation? substrate Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << H1-receptor >> antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which [[ histamine ]] is considered to be of pathogenic importance and conversely to help elucidate the role of histamine in disease, through an evaluation of their influence on disease expression. Query: What is the relation? agonist Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Query: What is the relation? upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Query: What is the relation? agonist-activator In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of [[ HSP70 ]] and Bax proteins. Query: What is the relation? indirect-upregulator These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and cdk2 [[ kinase ]] activities. Query: What is the relation? activator However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both MAO-A and << MAO-B >> by tranylcypromine together with the [[ monoamine ]] precursors. Query: What is the relation? inhibitor In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with rauwolscine, phentolamine, and [[ idazoxan ]]. Query: What is the relation? antagonist These results indicate that << U50,488H >>-induced down-regulation of the [[ hkor ]] involves GRK-, arrestin-2-, dynamin-, rab5-, and rab7-dependent mechanisms and receptors seem to be trafficked to lysosomes and proteasomes for degradation. Query: What is the relation? downregulator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of << Rasagiline >> (N-propargyl-1-(R)-aminoindan) is a novel, highly potent irreversible [[ monoamine oxidase (MAO)-B ]] inhibitor, anti-Parkinsonian drug. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 323,"The effect of sumatriptan, but not of LY 344864, was prevented by pretreatment with the antagonist << SDZ 21-009 >>, which displays high affinity for [[ rat 5-HT1B ]] receptors. what is the relation? antagonist Our results showed that low dose << BPA >> and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of [[ Oct4 ]] and Nanog proteins, while only BPA could downregulate the expression of E-cadherin protein. what is the relation? indirect-upregulator << Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line. what is the relation? upregulator << Fluoride >> treatment also increased phosphorylation of JNK and [[ ERK ]], but not p38, and apoptosis induced by fluoride was notably or partly suppressed by treatment with JNK or ERK inhibitors, respectively. what is the relation? activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and [[ BRCA2 ]] mutations, although preliminary evidence favors benefit for at least those with a BRCA2 mutation. what is the relation? downregulator Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. what is the relation? product-of Absorption and secretion of << fluoride >> increase at acid pH levels, possibly because of its non-ionized state at these pHs and/or because of participation of a F(-)/H(+) cotransporter or a [[ F(-)/OH(-) antiporter ]]. what is the relation? substrate The << A2A adenosine receptor >> agonist [[ CGS21680 ]] (C23H29N7O6.HCl.xH2O) (0.001-0.1 μM) did not alter NE oxidation currents. what is the relation? agonist Similar to gemfibrozil, clofibrate, another << fibrate >> drug, also inhibited the expression of [[ iNOS ]]. what is the relation? indirect-downregulator << Felbamate >> produced a rapid, concentration-dependent block of currents evoked by 50 microM NMDA and 10 microM glycine in human embryonic kidney 293 cells expressing the rat NR1a subunit, and either the [[ NR2A ]], NR2B or NR2C subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV). what is the relation? inhibitor The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. what is the relation? agonist-activator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). what is the relation? substrate_product-of Of note, we demonstrated for the first time that << telmisartan >> augmented [[ GLUT4 ]] protein expression and 2-deoxy glucose uptake both in basal and insulin-stimulated state of adipocytes, which may contribute, at least partly, to its insulin-sensitizing ability. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 324,"Regarding ""One major route involves the tetrahydrofolate (THF)-dependent activities of the glycine decarboxylase complex (GDC, EC 2.1.1.10) and serine hydroxymethyltransferase (SHMT, << EC 2.1.2.1 >>) with glycine ([[ Gly ]]) as one-carbon (1-C) source."", can you determine the relation? substrate Regarding ""<< Curcumin >> improves TNBS-induced colitis in rats by inhibiting IL-27 expression via the TLR4/[[ NF-κB ]] signaling pathway."", can you determine the relation? inhibitor Regarding ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", can you determine the relation? agonist-activator Regarding ""At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of [[ GluN1 ]]/GluN2B receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic."", can you determine the relation? downregulator Regarding ""The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists << SB224289 >> (300 microg/kg; [[ 5-HT1B ]]), BRL15572 (300 microg/kg; 5-HT1D), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C)."", can you determine the relation? antagonist Regarding ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""<< Nitrogen >>-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and [[ Bim ]]-mediated activation of the intrinsic apoptotic pathway."", can you determine the relation? activator Regarding ""In the DRN, brexpiprazole completely inhibited the firing of 5-HT neurons via << 5-HT1A >> agonism and was more potent than [[ aripiprazole ]] (ED50 = 230 and 700 mug/kg, respectively)."", can you determine the relation? agonist Regarding ""In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 ([[ IL-6 ]]), and prostaglandin E2 (PGE2) in activated BV-2 cells."", can you determine the relation? indirect-downregulator Regarding ""The positive correlation between vitamin A and immunoglobulin A concentrations might be the result of the << vitamin A >> inductive effect during [[ immunoglobulins A ]] synthesis."", can you determine the relation? upregulator Regarding ""Results: Our results demonstrate that treatment with << LBH589 >> leads to [[ NIS ]] RNA expression as shown by RT-PCR and luciferase assay, and to protein expression as determined by immunofluorescence in vitro and by immunohistochemistry in xenograft tumors."", can you determine the relation? indirect-upregulator Regarding ""During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and << cortisol >> via hydroxysteroid (11-β) dehydrogenase 1 ([[ HSD11B1 ]])."", can you determine the relation? product-of Regarding ""<< gamma-Butyrobetaine hydroxylase >> catalyse the last step in carnitine biosynthesis, the formation of [[ L-carnitine ]] from gamma-butyrobetaine, a reaction dependent on Fe2+, alpha-ketoglutarate, ascorbate and oxygen."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 325,"Question: What is the relation in the sentence ""The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (<< NF-κB >>) genes expression in [[ cisplatin ]] injected rats.""? indirect-downregulator Question: What is the relation in the sentence ""We conclude that << felbamate >> exhibits modest selectivity for NMDA receptors composed of [[ NR1a ]]/NR2B subunits.""? inhibitor Question: What is the relation in the sentence ""Although generally highly specific for << angiotensin II type 1 receptors >>, some ARBs, particularly [[ telmisartan ]], are partial agonists at peroxisome proliferator-activated receptor-γ.""? antagonist Question: What is the relation in the sentence ""Given these findings, a unified PK model including the inhibition of << MAO-A >>- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, [[ 5-MeO-DMT ]], and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models.""? substrate Question: What is the relation in the sentence ""The in vivo inhibitory effect of << harmaline >> on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified [[ CYP2D6 ]].""? downregulator Question: What is the relation in the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity.""? agonist-activator Question: What is the relation in the sentence ""BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific << alpha2-adrenoceptor >> agonists of the type such as [[ dexmedetomidine ]].""? agonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""Chronic consumption of << alcohol >> also stimulated abrupt increases in pro-inflammatory cytokines such as [[ nuclear factor (NF)-κB ]], tumor necrosis factor (TNF)-α and interleukin (IL)-1β in liver otherwise co-administration of CNF effectively suppressed production of these cytokines dose-dependently.""? activator Question: What is the relation in the sentence ""<< V(5+) >> also increased [[ serum hemoglobin ]] (Hb) levels in animals treated for 24 h.""? indirect-upregulator Question: What is the relation in the sentence ""On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]].""? upregulator Question: What is the relation in the sentence ""L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield [[ pyruvate ]] or 2-oxobutyrate.""? product-of Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Ergovaline inhibition of radioligand binding to the D2 dopamine receptor and << ergot alkaloid >> inhibition of vasoactive intestinal peptide ([[ VIP ]])-stimulated cyclic AMP production in GH4ZR7 cells, stably transfected with a rat D2 dopamine receptor, were evaluated.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 326,"Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. what is the relation? upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. what is the relation? agonist-activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and [[ inositol requiring enzyme 1α ]]. what is the relation? activator Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>[[ levobunolol ]] approximately carteolol>/=timolol>atenolol. what is the relation? antagonist A dose of 25 microg kg(-1) day(-1) of << formoterol >> elicited greater EDL and soleus hypertrophy than salmeterol, but resulted in similar [[ beta-adrenoceptor ]] downregulation. what is the relation? downregulator The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific). what is the relation? agonist << Thiazolidinediones >> are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferator-activated receptor gamma (PPAR(gamma)) and stimulating the expression of [[ insulin ]]-responsive genes involved in glucose and lipid metabolism. what is the relation? indirect-upregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. what is the relation? substrate_product-of Synthesis, molecular modeling and evaluation of novel << N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone >> derivatives as dual inhibitors for [[ cholinesterases ]] and Aβ aggregation. what is the relation? inhibitor Block of human NaV1.5 << sodium channels >>[[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin. what is the relation? substrate Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues. what is the relation? product-of << Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, [[ TNFalpha ]], VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60. what is the relation? indirect-downregulator << Progestin >> activation of [[ Src ]]/MAPK occurred outside the nucleus with the B isoform of PR that was distributed between the cytoplasm and nucleus, but not with PR-A that was predominantly nuclear. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 327,"METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist ([[ SB-207266 ]]) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects. Question: what is the relation? Answer: antagonist In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and [[ cytochrome P450 ]], compared to the CCl4 only group. Question: what is the relation? Answer: activator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor Gene expression profiling (GEP) of GIST-S, GIST-R cells and two IM resistant GIST patients demonstrated that << KIT >> is downregulated implying a major role in [[ IM ]] resistance. Question: what is the relation? Answer: indirect-downregulator << S1P >> activated phosphatidylinositol 3-kinase ([[ PI3K ]])/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells. Question: what is the relation? Answer: indirect-upregulator The aim of this study was to evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of the novel cyclooxygenase-2 (<< COX-2 >>) selective inhibitor lumiracoxib ([[ Prexige ]]), so that dose recommendations for clinical use can be provided. Question: what is the relation? Answer: inhibitor The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and [[ Dkk2 ]]) of the pathway. Question: what is the relation? Answer: downregulator We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase ([[ CHS ]]), and an antioxidant enzyme such as ascorbate peroxidase (APX). Question: what is the relation? Answer: product-of Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: << 4-methoxy-2-naphthylamide >> of L-alanine for [[ aminopeptidase N ]], 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B. Question: what is the relation? Answer: substrate << Dexamethasone >> (DEX), betamethasone (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]. Question: what is the relation? Answer: agonist << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of [[ p21 ]](WAF1/CIP1) and p53. Question: what is the relation? Answer: upregulator Moreover, we also demonstrate that << puerarin >> functions at least partially through activation of MEK/ERK and PI3K/[[ Akt ]] signaling. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 328,"Question: What is the relation in the sentence ""The use of << A3 receptor >> agonist [[ IB-MECA ]] attenuates EAP.""? agonist Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma.""? agonist-activator Question: What is the relation in the sentence ""<< ACTH >>-stimulated peak cortisol, delta cortisol, and [[ delta DHEA ]]-S levels are decreased during hyperthyroidism, probably due to increased turnover.""? product-of Question: What is the relation in the sentence ""Sulfhydration of << sulfonylurea receptor 2B >> (SUR2B) was induced by [[ NaHS ]] and colonic inflammation.""? activator Question: What is the relation in the sentence ""Moreover, protein and mRNA levels of DSS-induced proinflammatory << cytokines >> in colon, including TNF-α, IL-1β, IL-18, IL-17A and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]].""? indirect-downregulator Question: What is the relation in the sentence ""However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an N-methyl d-aspartate receptor ([[ NMDAR ]]) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting.""? antagonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""Phenytoin (diphenylhydantoin, << DPH >>) is an established [[ sodium channel ]] blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.""? inhibitor Question: What is the relation in the sentence ""Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and [[ Rspo3 ]]) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway.""? downregulator Question: What is the relation in the sentence ""The studies with dThyd rescue from << cyclin E >>-cdk2 protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance.""? indirect-upregulator Question: What is the relation in the sentence ""We confirm the correlation between higher << hCTR1 >> levels and higher [[ Pt ]]-drug uptake in tumor cells sensitive to the drug.""? substrate Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/[[ CIP1 ]]) and p53.""? upregulator Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Furthermore, the << AMPK >> activator 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide ([[ AICAR ]]) significantly inhibited ghrelin secretion.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 329,"Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Please explain the relation. agonist-activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of Favorable enzyme profiles (high TP and low << DPD >>) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS. Please explain the relation. product-of The in vivo inhibitory effect of harmaline on << CYP2D6 >>-catalyzed [[ bufotenine ]] formation was confirmed by in vitro study using purified CYP2D6. Please explain the relation. substrate << DNA methyltransferase 3a >> expression was increased in all [[ BPA ]] males and BPA 0.5 females and reduced in BPA 200 females. Please explain the relation. indirect-upregulator << Sorafenib >> (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/[[ ERK ]] pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Please explain the relation. inhibitor Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing [[ NF-κB ]] activity and induction of Nrf2-dependent HO-1 activity. Please explain the relation. downregulator Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, [[ cyclin D1 ]], MMP7, and c-Myc. Please explain the relation. indirect-downregulator In the rabbit pulmonary artery, << rilmenidine >> and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan. Please explain the relation. antagonist Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells. Please explain the relation. upregulator In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and << cytochrome P450 >>, compared to the [[ CCl4 ]] only group. Please explain the relation. activator Two beta(2)-agonists, formoterol and << salmeterol >>, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater [[ beta(2)-adrenoceptor ]] selectivity. Please explain the relation. agonist Using the << alpha 1-adrenoceptor >> subtype-selective antagonists chlorethylclonidine ([[ CEC ]]), WB4101, and 5-methyl-urapidil, we have examined the possible heterogeneity in the alpha 1-adrenoceptor populations in rabbit aorta. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 330,"Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""Expression of the dominant negative mutants << rab5A >>-N133I or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation."", can you determine the relation? downregulator Regarding ""<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of [[ p38 ]] mitogen-activated protein kinase (p38 MAPK)."", can you determine the relation? inhibitor Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", can you determine the relation? upregulator Regarding ""Similarly, pretreatment with << sulindac sulfide >> blocks the ability of EGF to induce ERK1/2 and Bad phosphorylation, but also down-regulates total [[ Bad ]] but not ERK1/2 protein levels."", can you determine the relation? indirect-downregulator Regarding ""<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS)."", can you determine the relation? product-of Regarding ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", can you determine the relation? agonist-activator Regarding ""Thus, << SFO >> contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and [[ IL-8 ]] and cell apoptosis in plaque."", can you determine the relation? activator Regarding ""The << M564G >> mutated CrAT showed higher activity toward longer chain [[ acyl-CoAs ]]: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA."", can you determine the relation? substrate Regarding ""However, combined treatment with cinobufagin and << SB216367 >> resulted in a significant reduction in p65 and an increase in cleaved-[[ PARP ]] in U2OS cells."", can you determine the relation? indirect-upregulator Regarding ""<< Terfenadine >> and astemizole are chemically unrelated to [[ histamine H1-receptor ]] antagonists such as diphenhydramine and chlorpheniramine."", can you determine the relation? antagonist Regarding ""Lisuride dose dependently decreased body temperature in rats with a potency similar to that of the selective << 5-HT(1A) >> agonist [[ LY 293284 ]]."", can you determine the relation? agonist Regarding ""<< Mn >> exposure (20 mg/kg) increased [[ p38 ]](MAPK) and Akt phosphorylation, but decreased DARPP-32-Thr-34 phosphorylation."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 331,"Given the text ""The potency of the antipsychotic drug, << risperidone >>, to antagonize [[ alpha 1A-adrenoceptor ]]-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 1-adrenoceptor subtype-discriminating antagonists."", describe the relation. antagonist Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", describe the relation. agonist-activator Given the text ""Re-feeding normal chow or a high << sucrose >> diet for 24 h after a 48-h fast increased both [[ ACS1 ]] and ACS4 protein expression 1.5-2.0-fold, consistent with inhibition studies."", describe the relation. indirect-upregulator Given the text ""<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, [[ TNFalpha ]], VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60."", describe the relation. indirect-downregulator Given the text ""<< Indomethacin >> completely antagonizes CA activity, i.e. abolishes the inhibitory effect of acetazolamide on [[ CA ]]."", describe the relation. activator Given the text ""Thus prolonged activation of NMDA receptors in hippocampal neurons reduced << GABAR δ subunit >> expression through [[ Ca2+ ]] entry and at least in part by ERK1/2 activation."", describe the relation. downregulator Given the text ""One of the enzymes responsible for the production of << KA >>, [[ kynurenine aminotransferase I ]] (KATI), also catalyses the reversible transamination of glutamine to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. product-of Given the text ""<< H1-receptor >> antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which histamine is considered to be of pathogenic importance and conversely to help elucidate the role of [[ histamine ]] in disease, through an evaluation of their influence on disease expression."", describe the relation. agonist Given the text ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", describe the relation. upregulator Given the text ""Several active analogues were also evaluated for their ability to block uptake of DA, << 5-HT >>, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-[[ hSERT ]], and HEK-hNET cells."", describe the relation. substrate Given the text ""The anti-hyperthermic effect of Lu AF21934 (5 mg/kg) in the SIH test was inhibited by the benzodiazepine receptor antagonist flumazenil (10 mg/kg) and was not serotonin-dependent, as it persisted in serotonin-deficient mice and upon blockade of either << 5-HT(1A) >> receptors by [[ WAY100635 ]], or 5-HT(2A/2C) receptors by ritanserin."", describe the relation. inhibitor Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", describe the relation. substrate_product-of Given the text ""<< CO >> treatment also inhibited LPS-induced NO production and iNOS expression via its inactivation of [[ NF-kappaB ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 332,"Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Using cultured human keratinocytes and diabetic rat model, the current study showed that high-<< glucose >> environment enhanced [[ IL-8 ]] production via epidermal growth factor receptor (EGFR) -extracelluar signal-regulated kinase (ERK) pathway in a reactive oxygen species (ROS)-dependent manner in keratinocytes."". Can you identify the relation? indirect-upregulator Consider the text ""Tumor-growth-promoting << cyclooxygenase-2 >> [[ prostaglandin E2 ]] pathway provides medulloblastoma therapeutic targets."". Can you identify the relation? product-of Consider the text ""In a recent study using protein-specific anti-acetyl lysine antibodies and immunological methods, we demonstrated the ability of << aspirin >> to acetylate the [[ tumor suppressor protein p53 ]]."". Can you identify the relation? activator Consider the text ""Separate << 5-aza-2'-deoxycytidine >> pretreatment or in combination with trichostatin A reduced (m)CpG and specific small interference RNAs targeting [[ Mecp2 ]] and Creb1 separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells."". Can you identify the relation? indirect-downregulator Consider the text ""A novel << benzo[d]imidazole >> derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of [[ NLRP3 ]] inflammasome."". Can you identify the relation? inhibitor Consider the text ""On the other hand, in patients with a mean serum << carvedilol >> level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l."". Can you identify the relation? downregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""Even though the activities of << MAT >> and GNMT were elevated, the concentration of liver [[ S-adenosylmethionine ]] was decreased (24%, p<0.001) and S-adenosylhomocysteine increased (113%, p<0.001) in the dwarf mice."". Can you identify the relation? substrate Consider the text ""Like other << NMDA receptor >> antagonists, [[ memantine ]] at high concentrations can inhibit mechanisms of synaptic plasticity that are believed to underlie learning and memory."". Can you identify the relation? antagonist Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""<< DEX >> enhanced the ratio [[ IFN-gamma ]]/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005)."". Can you identify the relation? upregulator Consider the text ""The identification of the << succinate receptor >> SUCNR1 in platelets is of particular interest, because physiologically relevant concentrations of [[ succinate ]] were shown to potentiate the effect of low doses of a variety of platelet agonists."". Can you identify the relation? agonist Consider the text ""Blocking EGFR signaling with the EGFR/HER-2 kinase inhibitor (KI) << GW572016 >> decreased the postradiation survival of irradiated [[ Ras ]]-transformed cells and normal cells but had no effect on the survival of unirradiated cells."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 333,"Question: What is the relation in the sentence ""8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor [[ bisindolylmaleimide I ]] (1 μM).""? indirect-upregulator Question: What is the relation in the sentence ""BACKGROUND: << Pranlukast >>, a [[ cysteinyl leukotriene receptor 1 ]] (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation.""? antagonist Question: What is the relation in the sentence ""The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific).""? agonist Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity.""? agonist-activator Question: What is the relation in the sentence ""<< Cobalt chloride >>, a typical [[ HIF ]] activator, induced the gene expression of CAR-target genes, including cyp2b9 and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver.""? activator Question: What is the relation in the sentence ""For determination of [PA+<< Pli >>]-activity, [[ arginine ]] was added after this incubation.""? substrate Question: What is the relation in the sentence ""The upregulation of calpain, << tBid >> and caspase-3 activity were further inhibited by treatment with [[ EGTA ]] in the presence of ALD.""? indirect-downregulator Question: What is the relation in the sentence ""<< DEX >> enhanced the ratio [[ IFN-gamma ]]/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005).""? upregulator Question: What is the relation in the sentence ""When DLD-1/FdUrd cells expressing increased TS mRNA were treated with FdUrd and F3(d)Thd for only 4 h, the resistance ratios of DLD-1/FdUrd cells to parental DLD-1 cells were markedly different for FdUrd and F3(d)Thd, suggesting that the cytotoxicity with short-time exposure to << F3(d)Thd >> is due to a mechanism other than [[ TS ]] inhibition, although the cytotoxicity of F3(d)Thd in the short-time is low compared to that of long-time exposure.""? inhibitor Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin.""? downregulator Question: What is the relation in the sentence ""Specificity of << zebrafish retinol saturase >>: formation of all-trans-13,14-dihydroretinol and [[ all-trans-7,8- dihydroretinol ]].""? product-of Question: What is the relation in the sentence ""All four << DCK >> proteins yielded comparable metabolic activity for Ara-C and [[ dFdC ]] monophosphorylation, except for DCK24Val, which demonstrated an approximately 2-fold increase (P < 0.05) in the intrinsic clearance of dFdC monophosphorylation due to a 40% decrease in K(m) (P < 0.05).""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 334,"Consider the text ""Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index."". Can you identify the relation? product-of Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""<< alpha-Tocopherol transfer protein >> (alpha-TTP), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma [[ alpha-tocopherol ]] level by mediating the secretion of alpha-tocopherol by the liver."". Can you identify the relation? substrate Consider the text ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported << NRF2 >> target genes in response to NRF2 inducers (sulforaphane, [[ tert-butylhydroquinone ]], cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."". Can you identify the relation? activator Consider the text ""<< Amitriptyline >> is a TrkA and [[ TrkB ]] receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity."". Can you identify the relation? agonist Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased [[ superoxide dismutase ]] (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control."". Can you identify the relation? downregulator Consider the text ""The positive correlation between vitamin A and << immunoglobulin A >> concentrations might be the result of the [[ vitamin A ]] inductive effect during immunoglobulins A synthesis."". Can you identify the relation? upregulator Consider the text ""Furthermore, N-<< BPs >> decreased the levels of [[ phosphorylated extracellular signal-regulated kinase ]] (ERK) and mTOR via suppression of Ras prenylation and enhanced Bim expression."". Can you identify the relation? indirect-downregulator Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."". Can you identify the relation? agonist-activator Consider the text ""Kynurenic acid (<< KA >>) is an endogenous [[ glutamate receptor ]] antagonist at the level of the different ionotropic glutamate receptors."". Can you identify the relation? antagonist Consider the text ""The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by << Tomudex >> indicate that increased [[ cyclin E ]]-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance."". Can you identify the relation? indirect-upregulator Consider the text ""Furthermore, << BRN-250 >> inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of [[ VEGF receptor 2 ]] (VEGFR2) and the activation of its downstream AKT pathway."". Can you identify the relation? inhibitor Consider the text ""CONCLUSIONS: Weight reduction with << sibutramine >> is associated with altered gastric functions and increased [[ peptide YY ]] and is significantly associated with SLC6A4 genotype."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 335,"Regarding the sentence ""The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and [[ Aβ1-42 ]] in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of amyloid precursor protein (APP)."", what is the relation? indirect-upregulator Regarding the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator Regarding the sentence ""In contrast, there was little change in mRNA levels for << GTP cyclohydrolase I >> (GTPCH), the rate limiting enzyme in synthesis of the [[ tetrahydrobiopterin ]] (BH4), the obligate cofactor for TPH."", what is the relation? product-of Regarding the sentence ""Such model of << Nox4 >> activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i.e., its potential redox regulation, and could also define new therapeutic targets in diseases in which [[ quinones ]] and Nox4 are implicated."", what is the relation? activator Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""It has been claimed that << hCTR1 >>, the human high affinity copper transporter, is the major entry pathway for [[ cDDP ]] and related drugs via a mechanism that mimics copper."", what is the relation? substrate Regarding the sentence ""Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, prazosin, [[ tamsulosin ]] and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials."", what is the relation? antagonist Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted ([[ DeltaKPQ ]]) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings."", what is the relation? downregulator Regarding the sentence ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively."", what is the relation? upregulator Regarding the sentence ""In contrast, the << D-1997 >>-induced responses were potently and concentration-dependently antagonized by the mixed [[ 5-HT1-like ]] and 5-HT2 receptor antagonist methiothepin (0.01-1 microM)."", what is the relation? agonist Regarding the sentence ""A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic [[ cholesterol esterase ]] (CEase) and acetylcholinesterase (AChE)."", what is the relation? inhibitor Regarding the sentence ""<< Genistin >> decreased myosin light chain kinase ([[ MLCK ]]) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects."", what is the relation? indirect-downregulator Regarding the sentence ""Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent << CYP3A >> inhibitors such as [[ ritonavir ]]- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 336,"<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Question: what is the relation? Answer: substrate_product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Question: what is the relation? Answer: agonist-activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor << PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases ([[ COX ]]) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). Question: what is the relation? Answer: product-of Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. Question: what is the relation? Answer: upregulator << QR2 >> catalyzes the two-electron reduction of menadione via the oxidation of N-alkylated or [[ N-ribosylated nicotinamides ]]. Question: what is the relation? Answer: substrate << Epi >> increased both WNT6/Wnt6 and [[ Cav1 ]] expression in human GC cells and within the tumor area of a murine model of GC (CEA424-SV40 TAg). Question: what is the relation? Answer: indirect-upregulator << Minocycline >> treatment prevents the formation of activated [[ caspase-3 ]], a known effector of apoptosis, as well as the appearance of a calpain cleaved substrate, a marker of excitotoxic/necrotic cell death. Question: what is the relation? Answer: indirect-downregulator << Alprenolol >> and BAAM at 10(-7), 3 x 10(-7), and 10(-6) M inhibited the cardiac stimulation response slightly, which is indicative of membrane-stabilizing activity independent of [[ beta-adrenoceptor ]] blockade. Question: what is the relation? Answer: inhibitor In the DRN, brexpiprazole completely inhibited the firing of 5-HT neurons via << 5-HT1A >> agonism and was more potent than [[ aripiprazole ]] (ED50 = 230 and 700 mug/kg, respectively). Question: what is the relation? Answer: agonist Little is known in terms of multi-matrix << cytochrome P450 >> activity induction under repeated oral exposure to planar [[ halogenated and polycyclic aromatic hydrocarbons ]] (PHH, PAH). Question: what is the relation? Answer: activator Previously, we showed that the human kappa-opioid receptor (<< hkor >>) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged [[ U50,488H ]] treatment. Question: what is the relation? Answer: downregulator Inhibition of binding of the << alpha2-receptor >> antagonist [[ [3H]RX821002 ]] to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro. Question: what is the relation? Answer: antagonist Two imidazoquinoline molecules, imiquimod and << gardiquimod >>, markedly activated both porcine TLR7 and [[ TLR8 ]] whereas only human TLR7, but not TLR8, was activated by the ligands. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 337,"Consider the text ""Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and [[ PSA ]] genes with and/or without dihydrotestosterone (DHT)."". Can you identify the relation? indirect-downregulator Consider the text ""In further studies, the diuretic effects of the << CB1 >> agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with [[ rimonabant ]], but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]."". Can you identify the relation? antagonist Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""They all expressed ASS, but not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the product of degradation of arginine with << rhArg >>, to [[ citrulline ]], which is converted back to arginine via ASS."". Can you identify the relation? product-of Consider the text ""Upon co-exposure to << V(5+) >> and TCDD, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."". Can you identify the relation? indirect-upregulator Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Taken together, these data demonstrate that baicalin inhibits the metabolism of << DXM >> in a concentration-dependent manner in rats, possibly through inhibiting hepatic [[ CYP2D ]] and CYP3A activities."". Can you identify the relation? substrate Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""In conclusion, of the seven NSAIDs investigated, << niflumic acid >> was the most potent inhibitor of recombinant [[ UGT1A9 ]] via 4-MUG in a competitive manner."". Can you identify the relation? inhibitor Consider the text ""Galanin attenuates cyclic AMP regulatory element-binding protein (<< CREB >>) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures."". Can you identify the relation? activator Consider the text ""<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and [[ phorbol 12-myristate 13-acetate ]] (PMA) in WEHI-231, HOP-92, and Colo-205 cells."". Can you identify the relation? downregulator Consider the text ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."". Can you identify the relation? upregulator Consider the text ""METHODS: Sedative and cardiovascular responses to etomidate and the alpha2-agonist, << dexmedetomidine >>, were determined in mice deficient in [[ alpha2-receptor ]] subtypes."". Can you identify the relation? agonist Consider the text ""Contribution of the << Na+-K+-2Cl- cotransporter >> NKCC1 to [[ Cl- ]] secretion in rat OMCD."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 338,"The positive correlation between << vitamin A >> and [[ immunoglobulin A ]] concentrations might be the result of the vitamin A inductive effect during immunoglobulins A synthesis. what is the relation? upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor As revealed by glucose oxidase (GOD) and radioimmunoassay (RIA), both << dimethyldiguanide >> (DC, 0.6gkg(-1)d(-1)) and CPS (0.3, 0.6, 1.2gkg(-1)d(-1)) treatments significantly resulted in down-regulation of blood glucose and [[ insulin ]] levels in serum, while the levels of oxidative stress markers were markedly lowered through ELISA assay. what is the relation? indirect-downregulator A series of phenolic acids and phenol natural products, such as << p-hydroxybenzoic acid >>, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1). what is the relation? inhibitor The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective << alpha(1D)-adrenoceptor >> antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively). what is the relation? agonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. what is the relation? substrate_product-of In this study, we investigated the presence of H(2)S and the expression of << H(2)S >> synthesizing enzymes, CSE and [[ CBS ]], in isolated mouse pancreatic acini. what is the relation? product-of To determine whether 3,4-methylenedioxymethamphetamine (<< MDMA >>)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured. what is the relation? downregulator << Statins >> increase [[ p21 ]] through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. what is the relation? indirect-upregulator The anticonvulsant << felbamate >> blocks N-methyl-D-asparate (NMDA) receptors but fails to exhibit the neurobehavioral toxicity characteristic of other [[ NMDA receptor ]] antagonists. what is the relation? antagonist Overall, although most anthocyanidins had no effects on AhR-CYP1A1 signaling, << pelargonidin >> can bind to and activate the [[ AhR ]] and AhR-dependent gene expression, and pelargonidin and delphinidin inhibit the CYP1A1 catalytic activity. what is the relation? activator Although a proton-stimulated uptake of << cefadroxil >> was demonstrated in PEPT2(+/+) mice (pH 6.5 versus pH 7.4; p < 0.01), no pH dependence was observed in [[ PEPT2 ]](-/-) mice. what is the relation? substrate Activation of << Atp8a1 >> is also reduced by these modifications; phosphatidylserine-O-methyl ester, [[ lysophosphatidylserine ]], glycerophosphoserine, and phosphoserine, which are not transported by the plasma membrane flippase, do not activate Atp8a1. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 339,"Regarding the sentence ""<< Labetalol >> (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the isoprenaline responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors."", what is the relation? antagonist Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""<< DBDCT >> also caused the phosphorylation of JNK and [[ p38 ]](MAPK)."", what is the relation? activator Regarding the sentence ""OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha ([[ PPARalpha ]]) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent."", what is the relation? agonist Regarding the sentence ""The inhibitory effect of << ginseng saponins >> on the stress-induced plasma [[ interleukin-6 ]] level in mice."", what is the relation? indirect-downregulator Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""Choline dehydrogenase (<< CHDH >>) and betaine-homocysteine methyltransferase (BHMT) are 2 enzymes involved in [[ choline ]] oxidation."", what is the relation? substrate Regarding the sentence ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (<< MSG >>, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased [[ pIR ]] by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", what is the relation? downregulator Regarding the sentence ""Further characterization of << sorafenib >> revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and [[ Kit ]]), which play key roles in tumor progression and angiogenesis."", what is the relation? inhibitor Regarding the sentence ""Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression and improved glucose tolerance parallel to [[ insulin ]] sensitivity in obese mice."", what is the relation? indirect-upregulator Regarding the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator Regarding the sentence ""Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity."", what is the relation? upregulator Regarding the sentence ""<< PGE(2) >> is synthesized from arachidonic acid by [[ cyclooxygenases ]] (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4)."", what is the relation? product-of Regarding the sentence ""In contrast, << aspirin >>-like nonselective NSAIDs such as sulindac and indomethacin inhibit not only the enzymatic action of the highly inducible, proinflammatory [[ COX-2 ]] but the constitutively expressed, cytoprotective COX-1 as well."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 340,"<< Beta-glucogallin >> reduces the expression of lipopolysaccharide-induced inflammatory markers by inhibition of [[ aldose reductase ]] in murine macrophages and ocular tissues. Query: What is the relation? inhibitor Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << CDCA >> induced dose-dependent expression of [[ Cdx2 ]] and MUC2 at both the mRNA and protein levels. Query: What is the relation? indirect-upregulator Pharmacology of << ramelteon >>, a selective MT1/[[ MT2 ]] receptor agonist: a novel therapeutic drug for sleep disorders. Query: What is the relation? agonist Follicle-stimulating hormone (<< FSH >>), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex [[ steroids ]] and gametes. Query: What is the relation? product-of However, combined treatment with cinobufagin and << SB216367 >> resulted in a significant reduction in [[ p65 ]] and an increase in cleaved-PARP in U2OS cells. Query: What is the relation? indirect-downregulator Both tolbutamide and gliclazide stimulated phospholipase C activity; however, only << gliclazide >> did so independently of its activity at [[ K(ATP) channels ]], and this activity was partially inhibited by pertussis toxin. Query: What is the relation? activator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). Query: What is the relation? downregulator The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the << 5-HT(2A) >>-receptor antagonist [[ ketanserin ]] was without effect. Query: What is the relation? antagonist The enzyme dimethylarginine dimethylaminohydrolase (<< DDAH >>) specifically hydrolyzes these asymmetrically methylated [[ arginine ]] residues to citrulline and methylamines. Query: What is the relation? substrate These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. Query: What is the relation? upregulator In this study, we demonstrate that << geldanamycin >> treatment blocks interleukin (IL)-2 secretion, [[ IL-2 receptor ]] expression, and proliferation of stimulated T-lymphocytes. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 341,"Regarding ""Carnitine acetyltransferases (<< CrAT >>) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", can you determine the relation? substrate Regarding ""Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized << KCNK1 >> as a [[ phenobarbital ]]-inducible antihyperplasia factor."", can you determine the relation? activator Regarding ""Only pMPPI [<< 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride >>], a selective [[ 5-HT(1A) ]] antagonist, was effective in inhibiting all 5-HT syndrome behaviors produced by lisuride, whereas pMPPI was without effect on any behavior induced by LSD."", can you determine the relation? antagonist Regarding ""<< Butein >> also increased [[ heme oxygenase-1 ]] (HO-1) protein expression and HO activity."", can you determine the relation? indirect-upregulator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", can you determine the relation? agonist-activator Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< Mouse brain serine racemase >> catalyzes specific elimination of L-serine to [[ pyruvate ]]."", can you determine the relation? product-of Regarding ""<< Statins >> increase p21 through inhibition of histone deacetylase activity and release of promoter-associated [[ HDAC1/2 ]]."", can you determine the relation? upregulator Regarding ""Concentration-dependent inhibitory effects of << baicalin >> on the metabolism of dextromethorphan, a dual probe of CYP2D and [[ CYP3A ]], in rats."", can you determine the relation? inhibitor Regarding ""<< HSYA >> suppressed the expression of TLR-4, [[ Myd88 ]], ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells."", can you determine the relation? indirect-downregulator Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and [[ histamine ]]."", can you determine the relation? agonist Regarding ""Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing NF-κB activity and induction of [[ Nrf2 ]]-dependent HO-1 activity."", can you determine the relation? downregulator Regarding ""<< CPT-11 >> and SN-38 may also stimulate the production of pro-inflammatory [[ cytokines ]] and prostaglandins (PGs), thus inducing the secretion of Na(+) and Cl(-)."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 342,"Furthermore, compared with control groups, the plaque endothelium level of p75(NTR) was 3-fold increased and the liver level of << p75(NTR) >> was 17.4-fold increased by [[ SFO ]]-HD. what is the relation? indirect-upregulator Effects of << ORF 17583 >>, other [[ histamine H2-receptor ]] antagonists and omeprazole on gastric acid secretory states in rats and dogs. what is the relation? antagonist Moreover, activities of caspase-3 and << caspase-9 >> enzymes were also significantly higher in both kinds of cells exposed to [[ SiO(2) ]] NPs. what is the relation? activator N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase (<< EC 3.1.4.45 >>; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome. what is the relation? product-of OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha (PPARalpha) and [[ PPARgamma ]] agonist, as a body-weight lowering, hypolipidemic and euglycemic agent. what is the relation? agonist In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins ([[ Rspo2 ]] and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. what is the relation? indirect-downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). what is the relation? substrate_product-of The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator Withdrawal from free-choice << ethanol >> consumption results in increased packing density of [[ glutamine synthetase ]]-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats. what is the relation? upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Suppression of Src/<< ERK >> and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells. what is the relation? downregulator << 4-Hydroxynonenal >> (4-HNE) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several [[ glutathione S-transferase ]] (GST) isoforms. what is the relation? substrate Preclinical pharmacokinetics and in vitro metabolism of dasatinib (<< BMS-354825 >>): a potent oral multi-targeted kinase inhibitor against SRC and BCR-[[ ABL ]]. what is the relation? inhibitor Metformin and << phenformin >>, which are biguanides, have been reported to increase [[ AMPK ]] activity without increasing AMP/ATP. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 343,"Consider the text ""Thus prolonged activation of NMDA receptors in hippocampal neurons reduced << GABAR δ subunit >> expression through [[ Ca2+ ]] entry and at least in part by ERK1/2 activation."". Can you identify the relation? downregulator Consider the text ""Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and [[ AM4054 ]] [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia."". Can you identify the relation? agonist Consider the text ""Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in [[ ERK1/2 ]] and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR."". Can you identify the relation? upregulator Consider the text ""Synthesis and Structure-Activity Relationship Studies of Derivatives of the Dual << Aromatase >>-Sulfatase Inhibitor [[ 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate ]]."". Can you identify the relation? inhibitor Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""<< L-proline >> accumulation and freeze tolerance of Saccharomyces cerevisiae are caused by a mutation in the PRO1 gene encoding [[ gamma-glutamyl kinase ]]."". Can you identify the relation? product-of Consider the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."". Can you identify the relation? agonist-activator Consider the text ""The concentration response to levcromakalim (<< LEVC >>), a [[ K(ATP) channel ]] opener, was significantly shifted to the left in the inflamed smooth-muscle cells."". Can you identify the relation? activator Consider the text ""<< Adenine phosphoribosyltransferase >> plays a role in purine salvage by catalyzing the direct conversion of [[ adenine ]] to adenosine monophosphate."". Can you identify the relation? substrate Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""Synthesis and antagonistic activity at << muscarinic receptor >> subtypes of some 2-carbonyl derivatives of [[ diphenidol ]]."". Can you identify the relation? antagonist Consider the text ""The lysosomal inhibitor << chloroquine >> significantly increased [[ RCAN1 ]] accumulation in +/+ cells, consistent with the hypothesis that higher lysosomal pH impairs RCAN1 degradation, leading to a higher RCAN1/NFATc1 ratio and consequently NFATc1 inhibition."". Can you identify the relation? indirect-upregulator Consider the text ""Inhibition of endogenous production of << H(2)S >> by PAG significantly suppressed SP concentration, PPT-A expression and [[ NK1-R ]] expression in the acini."". Can you identify the relation? indirect-downregulator Consider the text ""Liver << AOX >> activity was reduced by 45% with tungsten and 61% with [[ hydralazine ]] and 81% in AOX-deficient mice relative to controls."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 344,"Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512). Query: What is the relation? upregulator These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in [[ cyclin E ]] and cdk2 kinase activities. Query: What is the relation? activator Local LC citalopram effect was abolished by LC presence of the 5-HT3 receptor antagonist MDL72222 (1 μM) but not the << 5-HT1/2 >> receptor antagonist [[ methiothepin ]] (1 μM). Query: What is the relation? antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Aldose reductase >> (AR) catalyzes the reduction of toxic lipid aldehydes to their [[ alcohol ]] products and mediates inflammatory signals triggered by lipopolysaccharide (LPS). Query: What is the relation? product-of The mechanism of action of << Fc11a-2 >> was related to the inhibition of the cleavage of pro-caspase-1, pro-IL-1β and pro-IL-18 which in turn suppressed the activation of [[ NLRP3 ]] inflammasome. Query: What is the relation? inhibitor << Phillyrin >> strongly inhibited high glucose-induced fatty acid synthase ([[ FAS ]]) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation. Query: What is the relation? indirect-downregulator Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms. Query: What is the relation? downregulator Brexpiprazole reversed the inhibitory effect of the DA agonist << apomorphine >> on VTA DA neurons (ED50 = 61 mug/kg), whereas it was ineffective when administered alone, indicating partial agonistic action on [[ D2 receptors ]]. Query: What is the relation? agonist However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of metallothionein-II production, and an increase in p53 activation and the pro-apoptotic protein [[ Bax ]]. Query: What is the relation? indirect-upregulator RESULTS: (+/-)-, R-, and S-modafinil bind to the << DAT >> and inhibit [[ DA ]] uptake less potently than cocaine, with R-modafinil having approximately threefold higher affinity than its S-enantiomer. Query: What is the relation? substrate << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of Discovery of << aryl ureas >> and aryl amides as potent and selective [[ histamine H3 receptor ]] antagonists for the treatment of obesity (Part I). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 345,"In reference to ""Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats."", what is the relation? upregulator In reference to ""The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of [[ caspase-9 ]] and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways."", what is the relation? activator In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""Brain but not spinal << NR2B >> receptor is responsible for the anti-allodynic effect of an NR2B subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model."", what is the relation? antagonist In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""In the locus coeruleus, brexpiprazole reversed the inhibitory effect of the preferential << 5-HT2A >> receptor agonist DOI ([[ 2,5-dimethoxy-4-iodoamphetamine ]]) on norepinephrine neuronal firing (ED50 = 110 mug/kg), demonstrating 5-HT2A antagonistic action."", what is the relation? agonist In reference to ""Both << risperidone >> and 9-hydroxyrisperidone are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination."", what is the relation? substrate In reference to ""The studies with dThyd rescue from cyclin E-<< cdk2 >> protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance."", what is the relation? inhibitor In reference to ""Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2."", what is the relation? downregulator In reference to ""In addition, the number and area of glutathione S-transferase placental form (GST-P) positive foci and << proliferating cell nuclear antigen >> (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg [[ MEG ]] compared with the control animals."", what is the relation? indirect-upregulator In reference to ""The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of [[ nuclear factor-κB ]] (NF-κB) p65 and p50 subunits."", what is the relation? indirect-downregulator In reference to ""Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index."", what is the relation? product-of In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""In conclusion, OMCD tubules from deoxycorticosterone pivalate-treated rats secrete << Cl- >> into the luminal fluid through [[ NKCC1 ]]-mediated Cl- uptake across the basolateral membrane in series with Cl- efflux across the apical membrane."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 346,"Question: What is the relation in the sentence ""Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist [[ acetylcholine ]] (ACh) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump.""? agonist Question: What is the relation in the sentence ""Existing ion channel blockers, such as amiodarone, dronedarone, bepridil, aprindine, and << cibenzoline >>, have been found to have an [[ NCX ]] inhibitory action.""? inhibitor Question: What is the relation in the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].""? agonist-activator Question: What is the relation in the sentence ""Increased immunohistochemical labeling of HIF-1alpha, VEGF, and << BNP >> in the ventricular myocardium was observed in the shunt group and [[ carvedilol ]] again normalized the labeling.""? indirect-downregulator Question: What is the relation in the sentence ""The scientific basis of this treatment of ED includes relaxation of the corpus cavernosum smooth muscle tissue by inhibition of << PDE5 >> that breaks down [[ cGMP ]], the key pathway for the production of erectile function in humans.""? substrate Question: What is the relation in the sentence ""In HEK-293 cells stably transfected with this receptor, << serotonin >> elicits a potent stimulation of [[ adenylyl cyclase ]] activity, which is blocked by antipsychotic and antidepressant drugs.""? activator Question: What is the relation in the sentence ""Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms.""? downregulator Question: What is the relation in the sentence ""Risperidone is metabolized to its active metabolite, << 9-hydroxyrisperidone >>, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4.""? product-of Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme.""? upregulator Question: What is the relation in the sentence ""(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, << SNAP 1069 >> and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]].""? antagonist Question: What is the relation in the sentence ""Although Bak and Bcl-2-associated X protein (Bax), another member of the Bcl-2 family, are generally thought to be functionally redundant, only Bak is necessary and sufficient for << VK2 >>-induced cytochrome c ([[ cyt c ]]) release and cell death.""? indirect-upregulator Question: What is the relation in the sentence ""Among 12 parabens with linear alkyl chains ranging in length from C1 to C12, << heptylparaben >> (C7) and pentylparaben (C5) showed the most potent [[ ERα ]] and ERβ agonistic activity in the order of 10(-7)M and 10(-8)M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 347,"Given the text ""These results indicate that << U50,488H >>-induced down-regulation of the [[ hkor ]] involves GRK-, arrestin-2-, dynamin-, rab5-, and rab7-dependent mechanisms and receptors seem to be trafficked to lysosomes and proteasomes for degradation."", describe the relation. downregulator Given the text ""The putative alpha 1L-adrenoceptor antagonist JTH-601, but not the << alpha 1B-adrenoceptor >> antagonist [[ chloroethylclonidine ]] (10 microM) antagonized noradrenaline-induced contractions of SMA."", describe the relation. antagonist Given the text ""<< Pyrrolopyrazines >> as Selective [[ Spleen Tyrosine Kinase ]] Inhibitors."", describe the relation. inhibitor Given the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", describe the relation. agonist-activator Given the text ""Noradrenaline and << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively."", describe the relation. agonist Given the text ""<< Cholesterol >> uptake from [[ lipoproteins ]], intracellular vesicle transport and lipid transfer are also modified by oxysterols."", describe the relation. substrate Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""In four (10 %) patients the peak << ACTH >>-stimulated [[ cortisol ]] values were lower than 18 μg/dL."", describe the relation. product-of Given the text ""Saturated << palmitic and stearic acids >> increased ceramides, up-regulated [[ PTP1B ]], and had AKt and PTP1B phosphorylation at Ser 50 impaired."", describe the relation. upregulator Given the text ""I3A induced a higher level of secretion of the inflammatory << cytokine >> interleukin 6 compared with [[ PMA ]] in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction."", describe the relation. indirect-upregulator Given the text ""Western blotting demonstrated that << DMBT >> effectively suppressed the expression of VEGF, p-VEGFR-2, [[ p-EGFR ]], and p-Akt."", describe the relation. indirect-downregulator Given the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""<< EROD >> activity induction in peripheral blood lymphocytes, liver and brain tissues of rats orally exposed to [[ polycyclic aromatic hydrocarbons ]]."", describe the relation. activator Given the text ""GnRH stimulation of CREB phosphorylation (pCREB) in the gonadotrope-derived LβT2 cell line was attenuated by a << protein kinase A >> (PKA) inhibitor, [[ H89 ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 348,"Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", describe the relation. agonist-activator Given the text ""<< L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or [[ 2-oxobutyrate ]]."", describe the relation. product-of Given the text ""Reductive detoxification of << arylhydroxylamine >> carcinogens by human NADH cytochrome b5 reductase and [[ cytochrome b5 ]]."", describe the relation. substrate Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""Synthesis and structure-activity relationship of << pyripyropene A >> derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 ([[ ACAT2 ]]) inhibitors: Part 2."", describe the relation. inhibitor Given the text ""In addition, << Silibinin >> caused an increase in p53 and [[ p21 ]] protein level as well as mRNA levels."", describe the relation. indirect-upregulator Given the text ""<< [6]-gingerol >>: a novel [[ AT₁ ]] antagonist for the treatment of cardiovascular disease."", describe the relation. antagonist Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]]."", describe the relation. downregulator Given the text ""Evidence has accumulated in the last few years that the expression of the << microsomal/peroxidase antigen >> (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis."", describe the relation. upregulator Given the text ""<< 2-(2-Aminoethyl)-quinoline >> (D-1997): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", describe the relation. agonist Given the text ""Pasireotide (<< Signifor >>(®)) is a new subcutaneous somatostatin analogue that acts via somatostatin receptors to inhibit the secretion of [[ corticotropin ]] from the pituitary adenoma in patients with Cushing's disease."", describe the relation. indirect-downregulator Given the text ""Treatment with diclofenac resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated caspase-3 after 6 hr, indicating that << diclofenac >> may cause apoptosis of neuronal cells via activation of the [[ caspase ]] cascade."", describe the relation. activator Given the text ""Direct transport of << rifampicin >> could be shown for [[ OATP-C ]] (apparent K(m) value 13 micromol/L) and OATP8 (2.3 micromol/L)."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 349,"Depletion of putrescine, spermidine, and << spermine >> by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. Query: What is the relation? product-of << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, [[ c-Myc ]], and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Query: What is the relation? downregulator In addition, by comparing the combined administration of (+/-)pindolol with either WAY100635, GR127935 or isamoltane, we have determined that << (+/-)pindolol >> produces much of its acute potentiation of fluoxetine-induced increases in extracellular 5-HT via its action at the 5-HT(1B/D) receptor in addition to any activity it has at the presynaptic [[ 5-HT(1A) ]] receptor. Query: What is the relation? antagonist << Flutamide >>, an effective competitive inhibitor of the [[ androgen receptor ]] used orally for palliative treatment of prostatic carcinoma and regulation of prostatic hyperplasia was evaluated for its genotoxic effects in the intact rat and in primary cultures of human hepatocytes. Query: What is the relation? inhibitor Cotreatment with << U0126 >> and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, [[ JNK ]], and beta-catenin. Query: What is the relation? activator The positive correlation between vitamin A and << immunoglobulin A >> concentrations might be the result of the [[ vitamin A ]] inductive effect during immunoglobulins A synthesis. Query: What is the relation? upregulator At PND35, the medial prefrontal cortex (mPFC) of rats given << MPH >> showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter ([[ NET ]])-ir density. Query: What is the relation? indirect-downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor Mitiglinide (<< KAD-1229 >>), a new anti-diabetic drug, is thought to stimulate [[ insulin ]] secretion by closing the ATP-sensitive K+ (K(ATP)) channels in pancreatic beta-cells. Query: What is the relation? indirect-upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Query: What is the relation? agonist-activator Lisuride dose dependently decreased body temperature in rats with a potency similar to that of the selective << 5-HT(1A) >> agonist [[ LY 293284 ]]. Query: What is the relation? agonist Although glutathione S-transferase omega 1 (GSTO1) and << arsenic methyltransferase >> have been shown or thought to catalyze [[ DMAs(V) ]] reduction, their role in DMAs(V) reduction in vivo, or in cell extracts is uncertain. Query: What is the relation? substrate Reuptake of extracellular << noradrenaline >> (NA) into superior cervical ganglion (SCG) neurones is mediated by means of the [[ noradrenaline transporter ]] (NAT, uptake 1). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 350,"Given the text ""The potency of the antipsychotic drug, << risperidone >>, to antagonize alpha 1A-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and [[ alpha 1B-adrenoceptor ]]-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 1-adrenoceptor subtype-discriminating antagonists."", describe the relation. antagonist Given the text ""<< Enalkiren >> has been shown to produce dose-related suppression of plasma renin activity (PRA) and [[ angiotensin II ]] when administered intravenously."", describe the relation. inhibitor Given the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", describe the relation. agonist-activator Given the text ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and << 4-methoxy-2-naphthylamide >> of L-arginine for [[ aminopeptidase B ]]."", describe the relation. substrate Given the text ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport."", describe the relation. upregulator Given the text ""The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing [[ Bim ]] expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways."", describe the relation. indirect-upregulator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", describe the relation. substrate_product-of Given the text ""During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and << cortisol >> via [[ hydroxysteroid (11-β) dehydrogenase 1 ]] (HSD11B1)."", describe the relation. product-of Given the text ""The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", describe the relation. agonist Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""<< 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on [[ AMPK ]] consensus sites but did not change the amount of TSC1 bound to TSC2."", describe the relation. activator Given the text ""The inhibition of UG synthesis and << PR >> down-regulation by 5 alpha-NET and [[ 3 beta,5 alpha-NET ]] indicates that these NET metabolites possess antiprogestational properties."", describe the relation. indirect-downregulator Given the text ""On the other hand, in patients with a mean serum << carvedilol >> level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start ofcarvedilol therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l."", describe the relation. downregulator Given the text ""<< ABCA1 >>-facilitated [[ cholesterol ]] efflux and lipid parameters did not differ between equol-producing and non-equol-producing women."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 351,"Regarding ""The use of << A3 receptor >> agonist [[ IB-MECA ]] attenuates EAP."", can you determine the relation? agonist Regarding ""<< Gemfibrozil >>, a lipid-lowering drug, inhibits the induction of [[ nitric-oxide synthase ]] in human astrocytes."", can you determine the relation? inhibitor Regarding ""The ROS scavenger << N-acetyl l-cysteine >> and the mitochondrial antioxidant Mito-TEMPO rescued the inhibitory effect of cucurbitacin I on [[ Rac1 ]] activation."", can you determine the relation? activator Regarding ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", can you determine the relation? substrate_product-of Regarding ""Structural features of the central cannabinoid CB1 receptor involved in the binding of the specific << CB1 >> antagonist [[ SR 141716A ]]."", can you determine the relation? antagonist Regarding ""BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of glutamate to gamma-aminobutyric acid ([[ GABA ]])."", can you determine the relation? product-of Regarding ""<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and [[ phorbol 12-myristate 13-acetate ]] (PMA) in WEHI-231, HOP-92, and Colo-205 cells."", can you determine the relation? downregulator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", can you determine the relation? agonist-activator Regarding ""In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of << cAMP >> to AMP by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase."", can you determine the relation? substrate Regarding ""It has been reported that oligomeric << procyanidins >> of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and [[ insulin ]]-potentiating activities."", can you determine the relation? upregulator Regarding ""We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the << chenodeoxycholic acid >> (CDCA)-induced expression of [[ Cdx2 ]] and MUC2 in normal rat gastric epithelial cells (RGM-1 cells)."", can you determine the relation? indirect-upregulator Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of [[ Lef1 ]], Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD."", can you determine the relation? indirect-downregulator Regarding ""<< FMO3 >> overexpression in mice significantly increases plasma [[ TMAO ]] levels while silencing FMO3 decreases TMAO levels."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 352,"In reference to ""Inhibition of binding of the << alpha2-receptor >> antagonist [[ [3H]RX821002 ]] to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro."", what is the relation? antagonist In reference to ""<< DBDCT >> up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of [[ Bax ]]/Bcl-2."", what is the relation? indirect-upregulator In reference to ""Apple << polyphenols >> suppress antigen presentation of [[ ovalbumin ]] by THP-1-derived dendritic cells."", what is the relation? downregulator In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""<< Dexamethasone >> (DEX), betamethasone (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]."", what is the relation? agonist In reference to ""BACKGROUND: Rivastigmine is a << carbamate >> drug designed to inhibit both acetylcholinesterase and [[ butyrylcholinesterase ]] by reversibly covalently bonding to these enzymes."", what is the relation? inhibitor In reference to ""PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases (COX) and [[ prostaglandin E synthases ]] (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4)."", what is the relation? substrate In reference to ""PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (<< 5-FU >>) by thymidine phosphorylase ([[ TP ]]) inside target tissues."", what is the relation? product-of In reference to ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and << activating protein-1 >>, which were increased in [[ fructose ]]-fed rats."", what is the relation? upregulator In reference to ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of In reference to ""Subsequent analysis revealed that << cucurbitacin I >> strongly activates [[ RhoA ]] and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers."", what is the relation? activator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""A significant decrease in << HLA-DR >> expression was observed in the AP and fractionated [[ procyanidin ]]-treated cells in the presence of ovalbumin (OVA), but no effect on CD86 expression was observed."", what is the relation? indirect-downregulator In reference to ""Interestingly, following pBQN desensitization, wild-type TRPA1 had dramatically reduced response to the nonelectrophile agonist << carvacrol >>, whereas the triple cysteine mutant [[ TRPA1 ]] retained its full response."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",8,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist-activator 353,"For determination of << plasmin >> activity, 10 microL thereof was incubated with 150 microL 1.5 M [[ arginine ]], pH 8.7, and 100 microL 20 mM CT preoxidized (15 minutes 37 degrees C) pooled normal citrate buffered EDTA-plasma for 30 minutes (37 degrees C). what is the relation? substrate In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, [[ AP-1 ]], and ATF-2, together with the expression of HSP70 and Bax proteins. what is the relation? activator CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in [[ CYP1A1 ]] protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. what is the relation? upregulator Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [[[ 9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol ]]], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia. what is the relation? agonist Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of << fisetin >> on [[ mTOR ]]. what is the relation? downregulator The anti-inflammatory drugs sodium salicylate and << aspirin >> inhibited the activation of [[ NF-kappa B ]], which further explains the mechanism of action of these drugs. what is the relation? inhibitor To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, sodium hydrosulphide (<< NaHS >>), (10, 50 and 100 muM), that resulted in a significant increase in [[ SP ]] concentration and expression of PPT-A and NK1-R in acinar cells. what is the relation? indirect-upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of << (+/-)-tamsulosin >>, an [[ alpha 1A-adrenoceptor ]] antagonist, inhibits the positive inotropic effect but not the accumulation of inositol phosphates in rabbit heart. what is the relation? antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor In addition, << BGG >>-mediated inhibition of AR prevented LPS-induced activation of JNK and [[ p38 ]] and lowered ROS levels, which could inhibit LPS-induced apoptosis. what is the relation? indirect-downregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. what is the relation? agonist-activator PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by [[ thymidine phosphorylase ]] (TP) inside target tissues. what is the relation? product-of Sorafenib (<< BAY 43-9006 >>) is a small-molecule inhibitor that has been shown to target members of multiple classes of [[ tyrosine kinases ]] that are known to be involved in tumor cell proliferation and tumor angiogenesis. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 354,"Consider the text ""Expression of the dominant negative mutants rab5A-N133I or rab7-<< N125I >> blunted [[ U50,488H ]]-induced down-regulation."". Can you identify the relation? downregulator Consider the text ""These results suggest that << prostacyclin >> may play a role in downregulating [[ tissue factor ]] expression in monocytes, at least in part via elevation of intracellular levels of cyclic AMP."". Can you identify the relation? indirect-downregulator Consider the text ""Additionally, << MPTP >> significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in [[ Bax ]] expression, cytochrome C translocation to the cytosol, andcleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment."". Can you identify the relation? indirect-upregulator Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."". Can you identify the relation? agonist-activator Consider the text ""Effect of ramelteon (<< TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor performance in mice."". Can you identify the relation? agonist Consider the text ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."". Can you identify the relation? upregulator Consider the text ""The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and << 5-HT4 >> receptor antagonist ICS205930 ([[ tropisetron ]]; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM)."". Can you identify the relation? antagonist Consider the text ""To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive << arginase >> inhibitor [[ N(omega)-hydroxy-nor-L-arginine ]] (Nor-NOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs)."". Can you identify the relation? inhibitor Consider the text ""<< Mouse brain serine racemase >> catalyzes specific elimination of L-serine to [[ pyruvate ]]."". Can you identify the relation? product-of Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Sulfhydration of << sulfonylurea receptor 2B >> (SUR2B) was induced by [[ NaHS ]] and colonic inflammation."". Can you identify the relation? activator Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""The starting point for the calculations is the recent X-ray crystal structure of << GNMT >> complexed with [[ SAM ]] and acetate."". Can you identify the relation? substrate Consider the text ""Our results showed that bone remodeling was significantly decreased in CCL3(-/-) and CCR1(-/-) mice and in animals treated with << Met >>-RANTES (an antagonist of CCR5 and [[ CCR1 ]])."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 355,"Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific)."", what is the relation? agonist Regarding the sentence ""PURPOSE: The << fluoropyrimidine carbamate >> (capecitabine) is converted to 5-fluorouracil (5-FU) by [[ thymidine phosphorylase ]] (TP) inside target tissues."", what is the relation? substrate Regarding the sentence ""Consistent with these results, the translocation of cPLA2 protein as well as the release of << arachidonic acid >>, a principal product of [[ phospholipase A2 ]], was rapidly induced by the addition of C2-ceramide in a Rac-dependent manner."", what is the relation? product-of Regarding the sentence ""Peroxisome proliferator-activated receptor-α (PPARα) activation mimicked the effects of << resveratrol >> while PPARα inhibition prevented the effects of this [[ SIRT1 ]] activator."", what is the relation? activator Regarding the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", what is the relation? agonist-activator Regarding the sentence ""Structural optimization of << 2,5-thiophene amides >> as highly potent and selective [[ 17β-hydroxysteroid dehydrogenase type 2 ]] inhibitors for the treatment of osteoporosis."", what is the relation? inhibitor Regarding the sentence ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", what is the relation? downregulator Regarding the sentence ""In another experiment, << cyanopindolol >>, an antagonist of the [[ serotonin terminal autoreceptor ]], also prolonged the clearance of 5-HT from the CA3 region."", what is the relation? antagonist Regarding the sentence ""To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance."", what is the relation? upregulator Regarding the sentence ""Repression of << HDC >> gene expression and HDC activity by [[ dexamethasone ]] may underlie its therapeutic effect in the treatment of allergy."", what is the relation? indirect-downregulator Regarding the sentence ""Pretreatment of human breast carcinoma MCF-7 cells for 24 h with the groundnut extract and soybean << isoflavone >> increased gene expression of heme oxygenase-1 ([[ HO-1 ]]), a major antioxidative stress enzyme."", what is the relation? indirect-upregulator Regarding the sentence ""Therefore, decreases of PLK and << PNPO >> in the hippocampal CA1 region of aged brains may be involved in aging processes related with [[ gamma-aminobutyric acid ]] (GABA) function."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 356,"In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), [[ interleukin-1β ]] (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells. Question: what is the relation? Answer: indirect-downregulator The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and << 5-HT4 >> receptor antagonist ICS205930 ([[ tropisetron ]]; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM). Question: what is the relation? Answer: antagonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Question: what is the relation? Answer: substrate_product-of The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in [[ MSG ]]-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). Question: what is the relation? Answer: downregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor << Artemisinic acid >> inhibits melanogenesis through downregulation of [[ C/EBP α ]]-dependent expression of HMG-CoA reductase gene. Question: what is the relation? Answer: inhibitor << Nox4 >> oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific [[ quinone ]] derivatives could modulate this activity. Question: what is the relation? Answer: activator CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Question: what is the relation? Answer: upregulator Depletion of << putrescine >>, spermidine, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase ([[ ODC ]]) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. Question: what is the relation? Answer: product-of Stable << ABCC1 >>, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and ABCC2 the apical excretion of [[ BPDE glutathione ]] conjugates. Question: what is the relation? Answer: substrate The anti-amnesic effect of minaprine on the cycloheximide-induced memory impairment was also antagonized by a serotonin (5-HT) releaser, p-chloroamphetamine, and by a 5-HT precursor, 5-hydroxytryptophan, whereas a << 5-HT1A >>-selective agonist, [[ 8-hydroxy-2-(di-n-propylamino)tetralin ]], was inactive. Question: what is the relation? Answer: agonist << CYP1A1 >> and CYP1A2 mRNAs were also increased by [[ pelargonidin ]] in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Question: what is the relation? Answer: indirect-upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Question: what is the relation? Answer: agonist-activator Another inhibitor, brequinar was previously reported to be a slow-binding inhibitor of the human dihydroorotate dehydrogenase [W. Knecht, M. Loffler, Species-related inhibition of << human and rat dihyroorotate dehydrogenase >> by immunosuppressive isoxazol and [[ cinchoninic acid ]] derivatives, Biochem. Pharmacol. 56 (1998) 1259-1264]. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 357,"Regarding the sentence ""The 5-HT(1/2/5/7)-receptor antagonist methysergide and the << 5-HT(2A/2B/2C)-receptor >> antagonist [[ LY 53857 ]] enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it."", what is the relation? antagonist Regarding the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and [[ retinoblastoma protein ]] (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Saturated << palmitic and stearic acids >> increased ceramides, up-regulated [[ PTP1B ]], and had AKt and PTP1B phosphorylation at Ser 50 impaired."", what is the relation? upregulator Regarding the sentence ""<< ALD >> increased [[ calpain ]] expression and caspase-3 activity and promoted Bid cleavage."", what is the relation? indirect-upregulator Regarding the sentence ""Cotreatment with << U0126 >> and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, [[ JNK ]], and beta-catenin."", what is the relation? activator Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Specificity of << zebrafish retinol saturase >>: formation of all-trans-13,14-dihydroretinol and [[ all-trans-7,8- dihydroretinol ]]."", what is the relation? product-of Regarding the sentence ""Existing ion channel blockers, such as amiodarone, dronedarone, bepridil, aprindine, and << cibenzoline >>, have been found to have an [[ NCX ]] inhibitory action."", what is the relation? inhibitor Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves."", what is the relation? agonist Regarding the sentence ""In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), [[ lactic dehydrogenase ]] (LDH), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system."", what is the relation? indirect-downregulator Regarding the sentence ""Recombinant << PDE10A >> transfected and expressed in COS-7 cells hydrolyzed cAMP and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with [[ cAMP ]]."", what is the relation? substrate Regarding the sentence ""The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and << JNK >> activation were significantly prevented with [[ EHT ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 358,"Consider the text ""In addition, << ethanol >> induced degradation of DNA methyltransferases ([[ DNMT- ]]1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."". Can you identify the relation? downregulator Consider the text ""Polyclonal antisera to either << b5R >> or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl ([[ NHOH-4-ABP ]]) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP)."". Can you identify the relation? substrate Consider the text ""Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor ([[ AR ]]) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT)."". Can you identify the relation? indirect-downregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""Previous studies demonstrated that the << Group III mGlu receptor >>-selective orthosteric agonist, [[ LSP1-2111 ]] produced anxiolytic- but not antidepressant-like effects upon peripheral administration."". Can you identify the relation? agonist Consider the text ""The treatment of U937 cells with NRF2 inducers including << sulforaphane >> effectively elevated the expression of [[ AKR1B1, 1B10, 1C1, 1C2, and 1C3 ]]."". Can you identify the relation? indirect-upregulator Consider the text ""NFAT cooperates with c-Jun, a compound of the AP-1 complex, to activate target genes, and we also found that << PSE >> inhibited both [[ JNK ]] activation and AP-1 transcriptional activity."". Can you identify the relation? inhibitor Consider the text ""<< KCNK1 >>, a member of the family of two-pore K(+) ion channels, is specifically induced in the livers of male mice after [[ phenobarbital ]] treatment."". Can you identify the relation? activator Consider the text ""The antagonistic property of << rilmenidine >> at [[ human alpha(2A)-adrenoceptors ]] indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved."". Can you identify the relation? antagonist Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""Rats were fed experimental diets containing SPI or << casein >> as a [[ nitrogen ]] source."". Can you identify the relation? product-of Consider the text ""Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats."". Can you identify the relation? upregulator Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Inhibition of the leukotriene synthetase of rat basophil leukemia cells by diethylcarbamazine, and synergism between << diethylcarbamazine >> and piriprost, a [[ 5-lipoxygenase ]] inhibitor."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 359,"Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Also, << vinblastine >> enhances the phosphorylation of [[ Ras homologous protein A ]], the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α. what is the relation? activator The non-selective adenosine receptor antagonist (caffeine), and the selective << adenosine A1 receptor >> antagonist ([[ DPCPX ]]), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice. what is the relation? antagonist RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. what is the relation? agonist-activator Both << risperidone >> and 9-hydroxyrisperidone are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination. what is the relation? substrate The vascular protective effects of << kinsenoside >> were speculated to be attributed to oxidative stress inhibition and the reduction of [[ nuclear factor kappa B ]] (NF-κB) mRNA expression levels in high glucose conditions. what is the relation? indirect-downregulator This observation suggests that << MDMA >>-induced reductions in [[ SERT ]] density do not represent neuroadaptive responses to decreased levels of brain serotonin, but may occur in response to some other stimulus or to the neurotoxic effects of MDMA. what is the relation? downregulator Furthermore, tPA induced rapid << tyrosine >> phosphorylation on the beta subunit of LRP-1, which was followed by the activation of Mek1 and its downstream [[ Erk-1 and -2 ]]. what is the relation? indirect-upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS). what is the relation? product-of OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (<< AR >>) agonist ([[ dexmedetomidine ]]). what is the relation? agonist Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. what is the relation? upregulator INTRODUCTION: In this study, we examined the effects of the << alpha-glucosidase >> inhibitors [[ acarbose ]] and voglibose on postprandial plasma glucose and serum triglyceride levels in patients with type 2 diabetes mellitus. what is the relation? inhibitor In conclusion, these findings indicate that << [3H]SR 142948A >> is a new potent antagonist radioligand which recognizes with high affinity both neurotensin NT1 and [[ NT2 receptors ]] and represents thus an excellent tool to study neurotensin receptors in the rat brain. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 360,"Consider the text ""<< Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as [[ ketone ]] bodies."". Can you identify the relation? substrate Consider the text ""Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect of an << NR2B >> subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model."". Can you identify the relation? antagonist Consider the text ""OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha (PPARalpha) and [[ PPARgamma ]] agonist, as a body-weight lowering, hypolipidemic and euglycemic agent."". Can you identify the relation? agonist Consider the text ""To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance."". Can you identify the relation? upregulator Consider the text ""Although inhibition of << LH >> release can be achieved by [[ estrogen ]] and progestins, an optimal inhibitory effect on the prostate is obtained by the combined administration of the antiandrogen with an LHRH agonist that causes a specific blockage of testicular androgen biosynthesis as well as an inhibition of the LH responsiveness to LHRH."". Can you identify the relation? inhibitor Consider the text ""<< Indomethacin >> treatment led to an increase in lipid peroxidation, [[ glutathione peroxidase ]] and glucose-6-phosphate dehydrogenase activities and to a decrease in catalase activity and glutathione levels in gastric mucosa."". Can you identify the relation? activator Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""<< (125)I-Cyanopindolol >> saturation binding in Adv.beta(1) myocytes demonstrated approximately 18-fold increase in [[ beta(1)-adrenoceptors ]]."". Can you identify the relation? indirect-upregulator Consider the text ""The latter reaction, catalyzed by << aspartoacylase >> (ASPA), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter."". Can you identify the relation? product-of Consider the text ""Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased << AEG-1 >> induced by [[ ursolic acid ]] in HepG2 cells."". Can you identify the relation? indirect-downregulator Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."". Can you identify the relation? agonist-activator Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), [[ CDK4 ]], c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."". Can you identify the relation? downregulator Consider the text ""Troglitazone, << bosentan >> and glibenclamide inhibit the bile salt export pump ([[ Bsep ]]) which transports taurocholate into bile."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 361,"Regarding ""<< Leukotriene D4 >> induces cognitive impairment through enhancement of [[ CysLT₁ R ]]-mediated amyloid-β generation in mice."", can you determine the relation? activator Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", can you determine the relation? agonist-activator Regarding ""We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (<< CDCA >>)-induced expression of Cdx2 and [[ MUC2 ]] in normal rat gastric epithelial cells (RGM-1 cells)."", can you determine the relation? indirect-upregulator Regarding ""The beneficial role of 17beta-estradiol on blood pressure, cardiac hypertrophy, vascular << osteopontin >> expression, perivascular fibrosis, and impaired NO-dependent relaxation of isolated aortic rings was completely abrogated by coadministration of [[ medroxyprogesterone acetate ]]."", can you determine the relation? indirect-downregulator Regarding ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased [[ catalase ]] (CAT) activity compared with the control."", can you determine the relation? upregulator Regarding ""Dexamethasone (DEX), << betamethasone >> (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]."", can you determine the relation? agonist Regarding ""Moreover, use of the pharmacological AMP-activated protein kinase (<< AMPK >>) inhibitor [[ compound C ]] revealed that AMPK is essential for suppressing SREBP-1c expression in phillyrin-treated cells."", can you determine the relation? inhibitor Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""<< PIP5K1B >> encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2]."", can you determine the relation? product-of Regarding ""Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II."", can you determine the relation? substrate Regarding ""<< Kynurenic acid >> (KA) is an endogenous glutamate receptor antagonist at the level of the different [[ ionotropic glutamate receptors ]]."", can you determine the relation? antagonist Regarding ""In combination with << clofarabine >>, the ability of resveratrol to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment."", can you determine the relation? downregulator Regarding ""Therefore, we examined whether the << PDE5 >>-I [[ vardenafil ]] improves memory and executive functioning and affect electroencephalography (EEG) in healthy young adults."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 362,"Question: What is the relation in the sentence ""A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, << gallic acid >>, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1).""? inhibitor Question: What is the relation in the sentence ""As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and << xanthine oxidase >> was identified as the likely source of TES-stimulated [[ superoxide ]] production.""? product-of Question: What is the relation in the sentence ""The most potent compound, << D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid >> (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini.""? antagonist Question: What is the relation in the sentence ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and << activating protein-1 >>, which were increased in [[ fructose ]]-fed rats.""? upregulator Question: What is the relation in the sentence ""<< Type I deiodinase >>, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1.""? indirect-upregulator Question: What is the relation in the sentence ""Thus, in 158N cells, the ability of << oxysterols >> to trigger a mode of cell death by apoptosis involving [[ GSK-3 ]] and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains.""? activator Question: What is the relation in the sentence ""In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and catalase ([[ CAT ]])) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system.""? indirect-downregulator Question: What is the relation in the sentence ""<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons ([[ PAHs ]]), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.""? substrate Question: What is the relation in the sentence ""Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of << inducible nitric-oxide synthase >> by [[ 15-deoxy-Delta12,14-prostaglandin J2 ]].""? downregulator Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]].""? agonist-activator Question: What is the relation in the sentence ""alpha(1)-Adrenoceptor antagonists were tested against the << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach.""? agonist Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""Treatment with adenosine dialdehyde (AdOx), an inhibitor of transmethylation-suppressive adenosylhomocysteine (SAH) hydrolase (<< SAHH >>), enhanced the level of [[ SAH ]] and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 363,"Regarding the sentence ""<< CYP1A1 >> and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", what is the relation? upregulator Regarding the sentence ""In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and [[ Bax ]] proteins."", what is the relation? indirect-upregulator Regarding the sentence ""Transport by << OATP1B1 >> and OATP1B3 enhances the cytotoxicity of epigallocatechin 3-O-gallate and several [[ quercetin ]] derivatives."", what is the relation? substrate Regarding the sentence ""To further our understanding of how << fisetin >> negatively regulates [[ mTORC1 ]] signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells."", what is the relation? downregulator Regarding the sentence ""On the other hand, the accumulation of << Ser >> through the C1-THF synthase/[[ SHMT ]] pathway in glyD plants was 2.5-fold greater than that in WT plants."", what is the relation? product-of Regarding the sentence ""<< (+/-)-Tamsulosin >>, over the range of concentrations at which it antagonized the positive inotropic effect mediated by [[ alpha 1-adrenoceptors ]], did not affect the accumulation of [3H]inositol phosphates that was induced by 10 microM phenylephrine."", what is the relation? antagonist Regarding the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Western blotting demonstrated that << DMBT >> effectively suppressed the expression of VEGF, p-VEGFR-2, p-EGFR, and [[ p-Akt ]]."", what is the relation? indirect-downregulator Regarding the sentence ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", what is the relation? agonist-activator Regarding the sentence ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound [[ BT-07-4M ]], TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure."", what is the relation? activator Regarding the sentence ""Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist salbutamol 8 mg ([[ SAL ]]), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors."", what is the relation? agonist Regarding the sentence ""In ex vivo experiments with tumor cells from refractory chronic lymphoblastic leukemia, dose-dependent << CDK2 >> inhibition associated with apoptotic changes was seen at concentrations greater than 100 nM of [[ flavopiridol ]]."", what is the relation? inhibitor Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""The << aromatic amino acid hydroxylases >> represent a superfamily of structurally and functionally closely related enzymes, one of those functions being reversible inhibition by [[ catechol ]] derivatives."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 364,"We have examined the effect of dihydropyridine << Ca2+-channel >> blockers [[ felodipine ]] and nicardipine on CaMPDE. Question: what is the relation? Answer: inhibitor Expression of the dominant negative mutants rab5A-N133I or rab7-<< N125I >> blunted [[ U50,488H ]]-induced down-regulation. Question: what is the relation? Answer: downregulator 6-DHSG was metabolised by GSH to form a GSH conjugate (<< GS-6-DHSG >>) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of [[ glutathione-S-transferase ]] (GST). Question: what is the relation? Answer: product-of The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and << AH 6809 >> ([[ EP1 ]] and EP2 specific). Question: what is the relation? Answer: antagonist In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives (AA-861, [[ tBuBHQ ]], tBuBQ, and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines. Question: what is the relation? Answer: activator << Sphingosine-1-phosphate >> promotes the nuclear translocation of β-catenin and thereby induces [[ osteoprotegerin ]] gene expression in osteoblast-like cell lines. Question: what is the relation? Answer: indirect-upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Question: what is the relation? Answer: agonist-activator While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of [[ H1-receptor ]] antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity. Question: what is the relation? Answer: agonist One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of << CGP 12177A >> mediates cardiostimulation by activation of the 'putative' beta(4)-adrenoceptor; however, it has recently been reported that disruption of the [[ beta(1)-adrenoceptor ]] gene abolishes this effect. Question: what is the relation? Answer: upregulator We concluded that FDH has no direct role in the regulation of the above two pathways of Ser synthesis; the breakdown of << formate >> to CO(2) by the [[ FDH ]] reaction is the primary and preferred fate of the organic acid in Arabidopsis. Question: what is the relation? Answer: substrate Inhibition of mTOR by low dose << rapamycin >> decreases HG-induced Nox4 and [[ Nox1 ]], NADPH oxidase activity and podocyte apoptosis. Question: what is the relation? Answer: indirect-downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor CONCLUSIONS: The chemotactic responses toward << C5a >> were inhibited by [[ nedocromil sodium ]] at higher concentrations than were required in the priming studies (IC50 approximately 10 to 100 nmol/L). Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 365,"In reference to ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively."", what is the relation? upregulator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""The effects of PLZ on both amino acids and their << transaminases >> were blocked by pre-treatment with the MAO inhibitor [[ tranylcypromine ]]."", what is the relation? inhibitor In reference to ""It is concluded that << D-1997 >> contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the [[ 5-HT1A ]] or 5-HT1B receptor subtypes."", what is the relation? activator In reference to ""Although generally highly specific for angiotensin II type 1 receptors, some ARBs, particularly << telmisartan >>, are partial agonists at [[ peroxisome proliferator-activated receptor-γ ]]."", what is the relation? agonist In reference to ""With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited [[ p16 ]] mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control."", what is the relation? indirect-downregulator In reference to ""<< 8-pCPT-2'-O-Me-cAMP-AM >> potentiation of [[ insulin ]] secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 μM)."", what is the relation? indirect-upregulator In reference to ""We conclude that << mPGES1 >> mediates acid-induced increase in [[ PGE2 ]] production and cell proliferation."", what is the relation? product-of In reference to ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator In reference to ""The << bupropion >> metabolic ratio appears to detect known differences in [[ CYP2B6 ]] activity associated with genetic polymorphism, across different ethnic groups."", what is the relation? substrate In reference to ""Labetalol (> or = 3 x 10(-8) M) and << dilevalol >> (> or = 10(-8) M) caused surmountable antagonism of the isoprenaline responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors."", what is the relation? antagonist In reference to ""Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and [[ Rspo3 ]]) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway."", what is the relation? downregulator In reference to ""Furthermore, the activities of the two << torafugu PPARalphas >> were enhanced 4.3- and 7.6-fold by arachidonic acid, 4.4- and 5.2-fold by docosahexaenoic acid, and 6.7- and 8.0-fold by [[ eicosapentaenoic acid ]] each at 50 microM, respectively."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 366,"In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor << RORalpha >> ectopic expression activated the cAspAT gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by [[ rosiglitazone ]] treatment of adipocytes. what is the relation? indirect-upregulator Firstly, the V(max) of << GAD >> was increased when ApoCaM was present whereas the affinity for the substrate, [[ glutamate ]], was not affected. what is the relation? substrate The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator << Catalpol >> also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of [[ IκBα ]] and the nuclear localization of NF-κB. what is the relation? indirect-downregulator In contrast, the selective << beta2AR >> antagonists ICI-118,551 and [[ butoxamine ]] inhibited isoproterenol-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively). what is the relation? antagonist << Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of [[ polyamine ]] levels in human cells, as acetylation of spermidine and spermine triggers export or degradation. what is the relation? product-of Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.). what is the relation? upregulator Second, << probucol >>, an antiatherogenic compound reported to be an inactivator of [[ ABCA1 ]] reduced hepatic alpha-tocopherol secretion. what is the relation? downregulator The effects of the << adenosine A3 receptor >> agonist [[ IB-MECA ]] on sodium taurocholate-induced experimental acute pancreatitis. what is the relation? agonist << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. what is the relation? activator Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by << harmaline >> was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-[[ CYP2D6 ]] mouse models. what is the relation? inhibitor Sources of << L-arg >> include dietary proteins and endogenous synthesis by argininosuccinate synthetase and [[ argininosuccinate lyase ]]. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 367,"The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, [[ glutamine synthetase ]], glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings. Question: what is the relation? Answer: downregulator << Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase ([[ CBS ]]). Question: what is the relation? Answer: product-of Next, we examined the role of Rho family GTPases in the << ceramide >>-induced signalling to [[ SRE ]] activation. Question: what is the relation? Answer: activator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Question: what is the relation? Answer: agonist-activator Meanwhile, the serum level of KC (a functional homolog of IL-8 and the main proinflammatory << alpha chemokine >> in mice) in apoE(-/-) mice was up to 357pg/ml in [[ SFO ]]-HD treated group. Question: what is the relation? Answer: indirect-upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor The selective << betaAR >> agonist [[ isoproterenol ]] caused an enhancement of hippocampal CA3 network activity, as measured by an increase in frequency of spontaneous burst discharges recorded in the CA3 region. Question: what is the relation? Answer: agonist Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (SCF), and macrophage migration inhibitory factor (<< MIF >>)) were down-regulated by [[ artemisinic acid ]]. Question: what is the relation? Answer: indirect-downregulator These and other data have generated a working hypothesis that activation of the terminal serotonin autoreceptor enhances the kinetics of << 5-HT >> uptake through an effect on the [[ serotonin transporter ]]. Question: what is the relation? Answer: substrate << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/[[ CIP1 ]]) and p53. Question: what is the relation? Answer: upregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of (+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and << RS 17053 >> appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]. Question: what is the relation? Answer: antagonist Patch-clamp analysis using inside-out recording configuration showed that << mitiglinide >> inhibits the Kir6.2/[[ SUR1 ]] channel currents in a dose-dependent manner (IC50 value, 100 nM) but does not significantly inhibit either Kir6.2/SUR2A or Kir6.2/SUR2B channel currents even at high doses (more than 10 microM). Question: what is the relation? Answer: inhibitor Our purpose was to test the impact of single and/or combined treatment with the AT(1)-receptor blocker candesartan and the << HMG-CoA reductase >> inhibitor [[ rosuvastatin ]] on infarct size and neuroscore in transient cerebral ischemia in rats. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 368,"In conclusion, the production of << IL-4 >> and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by [[ DEX ]] than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma. Please explain the relation. indirect-downregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of [[ I-κBε ]] and nuclear translocation of c-Rel/p50 in alveolar epithelial cells. Please explain the relation. downregulator << H1-receptor >> antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which [[ histamine ]] is considered to be of pathogenic importance and conversely to help elucidate the role of histamine in disease, through an evaluation of their influence on disease expression. Please explain the relation. agonist PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to << 5-fluorouracil >> (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues. Please explain the relation. product-of << Ozone >> plus PM(2.5) exposure, however, induced CRP, IL-6, CK, [[ LDH ]] and MDA increase, SOD and HRV decrease significantly in a dose-response way. Please explain the relation. indirect-upregulator A series of 2-carbonyl analogues of the muscarinic antagonist << diphenidol >> bearing 1-substituents of different lipophilic, electronic, and steric properties was synthesized and their affinity for the [[ M2 and M3 muscarinic receptor ]] subtypes was evaluated by functional tests. Please explain the relation. antagonist The present results indicated that << N >>-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of [[ caspase-9 ]] and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways. Please explain the relation. activator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of << navitoclax >>, a selective inhibitor of both BCL-2 and BCL-2-like 1 ([[ BCL-X(L) ]]), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. Please explain the relation. inhibitor << Statins >> increase p21 through inhibition of histone deacetylase activity and release of promoter-associated [[ HDAC1/2 ]]. Please explain the relation. upregulator Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 ([[ hCES1 ]]) and 2 (hCES2). Please explain the relation. substrate BG also showed a protective effect in the presence of a << DNA polymerase beta >> inhibitor (cytosine arabinoside-3-phosphate, [[ Ara-C ]]), demonstrating that BG does not act through an anti-mutagenic mechanism of action involving DNA polymerase beta. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 369,"Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""Ginseng total << saponins >>, ginsenosides Rb2, Rg1 and Rd administered intraperitoneally attenuated the immobilization stress-induced increase in plasma [[ IL-6 ]] level."", describe the relation. indirect-downregulator Given the text ""Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as GluN1/GluN2B [[ N-Methyl-D-aspartate Receptor ]] Antagonists."", describe the relation. antagonist Given the text ""<< Carboxylesterases >> hydrolyze esters, amides, and thioesters to produce [[ carboxylic acids ]] and resulting alcohols, amines, and thiols, respectively."", describe the relation. product-of Given the text ""Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line."", describe the relation. upregulator Given the text ""In concert with these results, we highlighted that the secretion of pro-inflammatory << cytokine >> and NF-κB activation induced by [[ TCDD ]] can be mediated by elevation of [Ca(2+)]i in HAPI microglial cells."", describe the relation. activator Given the text ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", describe the relation. downregulator Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Sorafenib (BAY 43-9006, << Nexavar >>), a dual-action inhibitor that targets RAF/MEK/[[ ERK ]] pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature."", describe the relation. inhibitor Given the text ""Monocarboxylate transporters (<< MCTs >>) are proton-linked membrane carriers involved in the transport of monocarboxylates such as [[ lactate ]], pyruvate, as well as ketone bodies."", describe the relation. substrate Given the text ""<< Swertiamarin >> treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-γ and GLUT-4; however, there was a significant increase in the mRNA expression of [[ adiponectin ]]."", describe the relation. indirect-upregulator Given the text ""Pre-clinical pharmacology of zolmitriptan (<< Zomig >>; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine."", describe the relation. agonist Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", describe the relation. agonist-activator Given the text ""In conclusion, << nobiletin >> attenuates HGF-induced HepG2 cells metastasis involving both ERK and [[ PI3K ]]/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 370,"<< 4-Hydroxynonenal >> (4-HNE) is a mutagenic alpha,beta-unsaturated aldehyde produced during oxidative injury that is conjugated by several [[ glutathione S-transferase ]] (GST) isoforms. what is the relation? substrate Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and << midazolam >> (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively. what is the relation? activator Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats. what is the relation? upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor These findings suggest that << S1P >> activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including [[ alkaline phosphatase ]], probably relating to the inhibition of osteoclast formation and the mineralization, respectively. what is the relation? indirect-upregulator The contractions to 5-HT were inhibited by << ketanserin >> and alosetron indicating involvement of [[ 5-HT(2A) ]] and 5-HT(3) receptors, respectively. what is the relation? inhibitor Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=[[ timolol ]]>atenolol. what is the relation? antagonist RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. what is the relation? agonist-activator The << A2A adenosine receptor >> agonist CGS21680 ([[ C23H29N7O6.HCl.xH2O ]]) (0.001-0.1 μM) did not alter NE oxidation currents. what is the relation? agonist First, addition of apolipoprotein A-I (<< apoA-I >>), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner. what is the relation? product-of Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal [[ NGF ]], BDNF and ChAT that was eliminated by olanzapine treatment. what is the relation? indirect-downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of In addition, << ethanol >> induced degradation of DNA methyltransferases ([[ DNMT- ]]1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. what is the relation? downregulator Similar concentrations also inhibited the formation of leukotriene C4 (<< LTC4 >>) by [[ LTC synthetase ]], a detergent-solubilized cell free particulate enzyme from RBL cells which is capable of coupling LTA4 to glutathione. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 371,"In reference to ""Consistent with the weak transactivation activity of esterified-<< BM >> mediated by [[ rat GR ]], there were few side effects, evaluated by thymus involution and body weight loss, in an antigen-induced asthmatic model in rats."", what is the relation? agonist In reference to ""<< Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line."", what is the relation? upregulator In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."", what is the relation? substrate_product-of In reference to ""Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory cytokines, increased [[ adiponectin ]] expression and improved glucose tolerance parallel to insulin sensitivity in obese mice."", what is the relation? indirect-upregulator In reference to ""Block of human NaV1.5 << sodium channels >>[[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin."", what is the relation? substrate In reference to ""Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors ([[ Dkk1 ]] and Dkk2) of the pathway."", what is the relation? downregulator In reference to ""Efficacy and safety of the << dipeptidyl peptidase-4 >> inhibitor, [[ sitagliptin ]], in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin."", what is the relation? inhibitor In reference to ""The efficacy of << astemizole >>, a new, long acting, oral [[ histamine H1-receptor ]] antagonist was compared to placebo for the treatment of allergic rhinitis and conjunctivitis during the grass pollen season of 1982."", what is the relation? antagonist In reference to ""Thus, it can be suggested that the inhibitory action of << ginseng saponins >> against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking norepinephrine- and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage rather than in the brain."", what is the relation? indirect-downregulator In reference to ""These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in cyclin E and [[ cdk2 ]] kinase activities."", what is the relation? activator In reference to ""Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS)."", what is the relation? product-of In reference to ""These findings suggest that some of the deleterious effects of consumption of endophyte-infected tall fescue, which contains several << ergot alkaloids >> including ergovaline, may be due to [[ D2 dopamine receptor ]] activation."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 372,"The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific). what is the relation? agonist << Jaspamide >> also inhibited other channels including Cav1.2, [[ Cav3.2 ]], and HCN2; however, the Kv11.1 (hERG) channel was minimally affected. what is the relation? inhibitor << Multidrug resistance-associated proteins >> are involved in the transport of the [[ glutathione ]] conjugates of the ultimate carcinogen of benzo[a]pyrene in human Caco-2 cells. what is the relation? substrate Inhibition of << S-adenosylmethionine decarboxylase >> by a specific inhibitor [diethylglyoxal bis-(guanylhydrazone); DEGBG] led to depletion of [[ spermidine ]] and spermine with a significant accumulation of putrescine and induction of ODC. what is the relation? product-of The data show that << CP[c]Ph >> is less potent at inducing [[ CYP1A ]] gene expression in rainbow trout than benzo[a]pyrene (B[a]P), a well-known Ah-receptor agonist. what is the relation? indirect-upregulator Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms. what is the relation? downregulator Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats. what is the relation? upregulator Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. what is the relation? agonist-activator << GCS >> therapy results in reduced mRNA expression of interleukin-4 ([[ IL-4 ]]) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma. what is the relation? indirect-downregulator Local LC citalopram effect was abolished by LC presence of the 5-HT3 receptor antagonist MDL72222 (1 μM) but not the << 5-HT1/2 >> receptor antagonist [[ methiothepin ]] (1 μM). what is the relation? antagonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional [[ 5-HT1-like receptor ]], located to sensory nerves. what is the relation? activator The inhibitory effect of << galangin >> on theses pro-inflammatory [[ cytokines ]] was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 373,"Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor << I3A >> induced a higher level of secretion of the inflammatory cytokine [[ interleukin 6 ]] compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction. Question: what is the relation? Answer: indirect-upregulator Zolmitriptan (<< Zomig >>; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura. Question: what is the relation? Answer: agonist 4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were [[ UGT1A10 ]] followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs. Question: what is the relation? Answer: substrate Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, IL-18, IL-17A and << IFN-γ >>, were markedly suppressed by [[ Fc11a-2 ]]. Question: what is the relation? Answer: indirect-downregulator Galanin attenuates cyclic AMP regulatory element-binding protein (<< CREB >>) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures. Question: what is the relation? Answer: activator High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates [[ tuberin ]] and activates mTOR. Question: what is the relation? Answer: downregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of CPT I (<< carnitine palmitoyltransferase I >>) catalyses the conversion of palmitoyl-CoA into [[ palmitoylcarnitine ]] in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria. Question: what is the relation? Answer: product-of In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Question: what is the relation? Answer: agonist-activator Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. Question: what is the relation? Answer: upregulator The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (lorglumide, << CR 1409 >>), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini. Question: what is the relation? Answer: antagonist Interestingly, << gemfibrozil >> strongly inhibited the activation of [[ NF-kappaB ]], AP-1, and C/EBPbeta but not that of GAS in cytokine-stimulated astroglial cells. Question: what is the relation? Answer: inhibitor Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and << Sunitinib >> (SU 11248, Sutent) specific for VEGF receptor [[ kinase ]], AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 374,"Given the text ""In comparison to diphenylhydantoin, the novel chloro-substituted << alpha-hydroxyphenylamide >> compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of [[ Na(V)1.5 ]] channels with an IC(50) value of 14.5 microM."", describe the relation. inhibitor Given the text ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."", describe the relation. upregulator Given the text ""There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, << Ezrin >>, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells."", describe the relation. indirect-upregulator Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of VEGFand [[ MMP-9 ]], resulting from the inhibition of Akt pathway."", describe the relation. downregulator Given the text ""Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>[[ betaxolol ]] approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>atenolol."", describe the relation. antagonist Given the text ""PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase β type I (<< pip5k1β >>), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2]."", describe the relation. product-of Given the text ""Moreover, LTD4-induced increases in CysLT(1)R and NF-κB << p65 >> in the brain were also attenuated by [[ pranlukast ]]."", describe the relation. indirect-downregulator Given the text ""OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a [[ peroxisome proliferator-activated receptor alpha ]] (PPARalpha) and PPARgamma agonist, as a body-weight lowering, hypolipidemic and euglycemic agent."", describe the relation. agonist Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", describe the relation. agonist-activator Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""<< Gemfibrozil >> induced [[ peroxisome proliferator-responsive element ]] (PPRE)-dependent luciferase activity, which was inhibited by the expression of DeltahPPAR-alpha, the dominant-negative mutant of human PPAR-alpha."", describe the relation. activator Given the text ""Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released << glutamate >> and its conversion to glutamine through the enzyme glutamine synthetase ([[ GS ]])."", describe the relation. substrate Given the text ""In HaCaT cells, buthanol and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, << clerosterol >> (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), [[ inducible nitric oxide synthase ]] (iNOS), and tumor necrosis factor-α (TNF- α)."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 375,"Consider the text ""In vitro accumulation studies conducted in Madin-Darby canine kidney II cells indicate that << dabrafenib >> is an avid substrate for both [[ P-gp ]] and BCRP."". Can you identify the relation? substrate Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."". Can you identify the relation? upregulator Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""The enzyme << cyclo-oxygenase >> catalyses the oxygenation of arachidonic acid, leading to the formation of [[ prostaglandins ]]."". Can you identify the relation? product-of Consider the text ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and << AH 6809 >> ([[ EP1 ]] and EP2 specific)."". Can you identify the relation? antagonist Consider the text ""In conclusion, of the seven NSAIDs investigated, << niflumic acid >> was the most potent inhibitor of recombinant [[ UGT1A9 ]] via 4-MUG in a competitive manner."". Can you identify the relation? inhibitor Consider the text ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists << SC-51089 >> (EP1 specific) and AH 6809 ([[ EP1 ]] and EP2 specific)."". Can you identify the relation? agonist Consider the text ""<< DBDCT >> also caused the phosphorylation of [[ JNK ]] and p38(MAPK)."". Can you identify the relation? activator Consider the text ""<< CDCA >> induced dose-dependent expression of Cdx2 and [[ MUC2 ]] at both the mRNA and protein levels."". Can you identify the relation? indirect-upregulator Consider the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."". Can you identify the relation? agonist-activator Consider the text ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]]."". Can you identify the relation? downregulator Consider the text ""<< PR mRNA >> abundance in both myometruim and leiomyomata (center and marginal area) was significantly decreased in 4 patients continuing [[ mifepristone ]] treatment before the operation but not in the other 2 patients stopping RU486 1 month before operation."". Can you identify the relation? indirect-downregulator Consider the text ""The presence of << steroid >> hormones most probably causes the degradation of the [[ Tat2 ]] permease and impairment of tryptophan import."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 376,"It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of [[ I-κBε ]] and nuclear translocation of c-Rel/p50 in alveolar epithelial cells. Query: What is the relation? downregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor In order to examine the site of action of an << NR2B >> subtype-selective NMDA antagonist [[ CP-101,606 ]], we investigated its analgesic effect in a rat model of neuropathic pain at various routes of administration. Query: What is the relation? antagonist CONCLUSIONS: Our results show that << indomethacin >>, a known cyclooxygenase (COX) inhibitor, is also an activator of [[ CA ]]. Query: What is the relation? activator In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (<< NDGA >>), a [[ lipoxygenase ]] inhibitor on human lung cancer cell lines. Query: What is the relation? inhibitor These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. Query: What is the relation? upregulator << Phillyrin >> strongly inhibited high glucose-induced [[ fatty acid synthase ]] (FAS) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation. Query: What is the relation? indirect-downregulator METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of << [(3)H] dopamine >> (DA) uptake and [(3)H]WIN 35428 binding in human dopamine transporter ([[ DAT ]]) wild-type and mutants with altered conformational equilibria. Query: What is the relation? substrate In this study, using reverse transcriptase PCR (RT-PCR) and ELISA, we showed that << TCDD >> up-regulated the expression and secretion of tumor necrosis factor-alpha ([[ TNF-α ]]) in a time-dependent manner in cultured HAPI microglial cells. Query: What is the relation? indirect-upregulator In four (10 %) patients the peak << ACTH >>-stimulated [[ cortisol ]] values were lower than 18 μg/dL. Query: What is the relation? product-of Thus, << amitriptyline >> acts as a [[ TrkA ]] and TrkB agonist and possesses marked neurotrophic activity. Query: What is the relation? agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Query: What is the relation? substrate_product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Query: What is the relation? agonist-activator << Apocynin >> and raisanberine alleviate intermittent hypoxia induced abnormal StAR and 3β-HSD and low testosterone by suppressing endoplasmic reticulum stress and activated [[ p66Shc ]] in rat testes. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 377,"Consider the text ""In relation to zinc bioavailability, α-CPPs, β-CPPs, α(s1)-CN(64-74)4P and << β-CN >>(1-25)4P increased [[ zinc ]] uptake."". Can you identify the relation? substrate Consider the text ""To this end, 158N murine oligodendrocytes were treated with << 7KC >> or 7βOHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving [[ Mcl-1 ]], and caspase-3 activation."". Can you identify the relation? activator Consider the text ""The putative << alpha 1L-adrenoceptor >> antagonist [[ JTH-601 ]], but not the alpha 1B-adrenoceptor antagonist chloroethylclonidine (10 microM) antagonized noradrenaline-induced contractions of SMA."". Can you identify the relation? antagonist Consider the text ""Moreover, a normal level of expression of PSS1 and/or << PSS2 >> is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis."". Can you identify the relation? product-of Consider the text ""These findings suggest that << S1P >> activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of [[ β-catenin ]] in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively."". Can you identify the relation? indirect-upregulator Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."". Can you identify the relation? upregulator Consider the text ""<< P2Y(2) receptor >> agonist [[ INS37217 ]] enhances functional recovery after detachment caused by subretinal injection in normal and rds mice."". Can you identify the relation? agonist Consider the text ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."". Can you identify the relation? agonist-activator Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""SC-51089 (10(-5) M), a selective EP1-receptor antagonist, showed no effect on the PGE1- or PGE2-induced inhibition of the HVA ICa, thereby indicating that << PGE1 >>- and PGE2-induced inhibition of the [[ HVA Ca2+ channels ]] is possibly mediated by the EP3 receptor."". Can you identify the relation? inhibitor Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and [[ retinoblastoma protein ]] (pRb), and the upregulation of p21(WAF1/CIP1) and p53."". Can you identify the relation? downregulator Consider the text ""In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α ([[ TNF-α ]]), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells."". Can you identify the relation? indirect-downregulator Consider the text ""<< BCRP >> appeared to play a more important role for absorption and intestinal and renal elimination of [[ apixaban ]] than P-gp in transporter-KO rats after oral and i.v. dosing, which led to a higher level of active renal excretion in rat than other species."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 378,"One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Firstly, transgenic plants overexpressing formate dehydrogenase (FDH, << EC 1.2.1.2 >>) were used to continue our previous studies on the function of FDH in [[ formate ]] metabolism. Question: what is the relation? Answer: substrate CONCLUSION: A long-term intake of ethanol solution down-regulates the phosphorylation of << CREB >> in the nucleus accumbens, and those changes can be reversed by [[ naloxone ]], which may be one kind of the molecular mechanisms associated with ethanol dependence. Question: what is the relation? Answer: upregulator The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Question: what is the relation? Answer: agonist-activator In patients who do not reach the LDL-C target, combination therapy with additional << LDL >>-C lowering drugs (e.g. [[ ezetimibe ]], bile acid sequestrants or fibrates) should be considered. Question: what is the relation? Answer: inhibitor In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and [[ cytochrome P450 ]], compared to the CCl4 only group. Question: what is the relation? Answer: activator In vivo << lorglumide >> antagonizes the contraction of the gall bladder of the guinea pig and of the dog provoked by i.v. [[ CCK-8 ]] or ceruletide (caerulein). Question: what is the relation? Answer: antagonist << Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and [[ receptor for AGE ]] (RAGE). Question: what is the relation? Answer: indirect-downregulator In contrast, the selective << beta2AR >> antagonists ICI-118,551 and butoxamine inhibited [[ isoproterenol ]]-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively). Question: what is the relation? Answer: agonist The obtained results showed that << pioglitazone >> improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), [[ nuclear factor kappa B ]] (NF-κB) genes expression in cisplatin injected rats. Question: what is the relation? Answer: indirect-upregulator Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]. Question: what is the relation? Answer: downregulator Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released glutamate and its conversion to << glutamine >> through the enzyme [[ glutamine synthetase ]] (GS). Question: what is the relation? Answer: product-of However, in vitro experiments simulating a uremic milieu revealed a marked concentration-dependent inhibition of << arginase >> activity by [[ urea ]] in the tissue lysates. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 379,"Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor The mechanism of action of << Fc11a-2 >> was related to the inhibition of the cleavage of pro-caspase-1, pro-IL-1β and [[ pro-IL-18 ]] which in turn suppressed the activation of NLRP3 inflammasome. Question: what is the relation? Answer: indirect-downregulator Histamine content, << HDC >> activity and HDC mRNA expression in nasal mucosa were also significantly increased after [[ TDI ]] provocation. Question: what is the relation? Answer: activator Polyclonal antisera to either b5R or << cyt b5 >> significantly inhibited [[ N-hydroxy-4-aminobiphenyl ]] (NHOH-4-ABP) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP). Question: what is the relation? Answer: substrate Combination treatment with the selective << 5-HT1A >> antagonist [[ WAY100635 ]] produced a dose-dependent augmentation of venlafaxine-induced (3-30 mg/kg s.c) extracellular 5-HT concentrations, but had no further effect on NA above that produced by venlafaxine alone. Question: what is the relation? Answer: antagonist << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Question: what is the relation? Answer: substrate_product-of The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific). Question: what is the relation? Answer: agonist These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of [[ VEGF ]]and MMP-9, resulting from the inhibition of Akt pathway. Question: what is the relation? Answer: downregulator These data demonstrated that 1) gemcitabine and pemetrexed synergistically interact against NSCLC cells through the suppression of Akt phosphorylation and induction of apoptosis; 2) the gene expression profile of critical genes may predict for drug chemosensitivity; and 3) << pemetrexed >> enhances dCK and [[ hENT1 ]] expression, thus suggesting the role of gene-expression modulation for rational development of chemotherapy combinations. Question: what is the relation? Answer: indirect-upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Question: what is the relation? Answer: agonist-activator Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner. Question: what is the relation? Answer: upregulator << Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of [[ polyamine ]] levels in human cells, as acetylation of spermidine and spermine triggers export or degradation. Question: what is the relation? Answer: product-of << Curcumin >> improves TNBS-induced colitis in rats by inhibiting IL-27 expression via the TLR4/[[ NF-κB ]] signaling pathway. Question: what is the relation? Answer: inhibitor Coumarin 7-hydroxylation, catalyzed by << P450 2A13 >>, was strongly inhibited by 2'-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, [[ chrysin ]], 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 380,"Regarding the sentence ""Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), << 17-phenyl-trinor-PGE2 >> (an [[ EP1 ]]-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2."", what is the relation? agonist Regarding the sentence ""<< Voltage-gated sodium (Na) channels >>[[ sodium ]] (Na) channels are a critical component of electrically excitable cells."", what is the relation? substrate Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""These results indicate that << phillyrin >> prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/[[ AMPK ]] activation, suggesting that phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity."", what is the relation? activator Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", what is the relation? substrate_product-of Regarding the sentence ""PURPOSE: To compare phenelzine (<< PLZ >>), an antidepressant drug with anxiolytic properties which inhibits [[ monoamine oxidase ]] (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T)."", what is the relation? inhibitor Regarding the sentence ""Thymidine kinase-1 (TK-1) and thymidylate synthase (<< TS >>) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively."", what is the relation? product-of Regarding the sentence ""CONCLUSION: A long-term intake of ethanol solution down-regulates the phosphorylation of << CREB >> in the nucleus accumbens, and those changes can be reversed by [[ naloxone ]], which may be one kind of the molecular mechanisms associated with ethanol dependence."", what is the relation? upregulator Regarding the sentence ""Thus, the << TCDD >>-induced reduction in canonical [[ Wnt ]] signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway."", what is the relation? indirect-downregulator Regarding the sentence ""Only pMPPI [<< 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride >>], a selective [[ 5-HT(1A) ]] antagonist, was effective in inhibiting all 5-HT syndrome behaviors produced by lisuride, whereas pMPPI was without effect on any behavior induced by LSD."", what is the relation? antagonist Regarding the sentence ""<< OMT >> showed partial protection in the cortical neurons via down-regulation of NR2B containing [[ NMDA receptors ]] and up-regulation of Bcl-2 family."", what is the relation? downregulator Regarding the sentence ""The << hemoglobin A1c >> (HbA1c) of all patients improved significantly from 8.1±1.2% to 7.6±1.1% after 12 weeks of add-on therapy with [[ sitagliptin ]] (p<0.01), and the insulin dosage was reduced from 27.3±15.8 U/day to 24.5±16.5 U/day (p<0.001)."", what is the relation? indirect-upregulator Regarding the sentence ""The nonselective and irreversible << MAO >> inhibitors, phenelzine (3-10 mg/kg), tranylcypromine (1-3 mg/kg), and [[ nialamide ]] (30 mg/kg), decreased rates of responding maintained by ethanol reinforcement."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 381,"It is concluded that << labetalol >> and dilevalol are [[ beta 1-adrenoceptor ]] selective antagonists. Please explain the relation. antagonist We observed a significant reduction in CSE induced luciferase expression, NF-κB DNA binding, << I-κBε >> degradation and c-Rel nuclear translocation in cells pretreated with [[ vitamin C ]]. Please explain the relation. downregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Prostaglandin E1, E2, STA2 (a stable analogue of << thromboxane A2 >>), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. Please explain the relation. indirect-downregulator These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. Please explain the relation. upregulator As far as we are aware, the compound's << 1,3,5-triazine >> scaffold represents a new core structure for [[ CB2 ]] agonists. Please explain the relation. agonist << Orlistat >> treatment also results in modest improvements in total cholesterol, low-density lipoprotein, blood pressure, and fasting glucose and [[ insulin ]] concentrations. Please explain the relation. indirect-upregulator Here, we demonstrate that << peptidyl-prolyl cis/trans-isomerase A1 >> (Pin1), an enzyme that catalyzes the conversion of the peptide bond of pSer/pThr-[[ Pro ]] moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification. Please explain the relation. substrate Upon activation by << phenobarbital >>, nuclear receptor [[ CAR ]] binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter. Please explain the relation. activator Troglitazone inhibited LTB(4) production by the supernatant fraction of RBL-2H3 cell lysate with similar potency to zileuton, suggesting that << troglitazone >> inhibits LT production by direct inhibition of [[ 5-LOX ]] activity. Please explain the relation. inhibitor One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS. Please explain the relation. product-of Agonist and antagonist actions of << yohimbine >> as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin [[ (5-HT)(1A) ]], 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 382,"Compared pharmacological characteristics in humans of racemic cetirizine and << levocetirizine >>, two [[ histamine H1-receptor ]] antagonists. Question: what is the relation? Answer: antagonist METHODS: Sedative and cardiovascular responses to etomidate and the alpha2-agonist, << dexmedetomidine >>, were determined in mice deficient in [[ alpha2-receptor ]] subtypes. Question: what is the relation? Answer: agonist << Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity. Question: what is the relation? Answer: upregulator Weekly subcutaneous << decitabine >> produces cumulative increases in [[ HbF ]] and total hemoglobin through a noncytotoxic mechanism of action. Question: what is the relation? Answer: indirect-upregulator In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the [[ methyl CpG-binding proteins ]] (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway. Question: what is the relation? Answer: downregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: agonist-activator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of To this end, 158N murine oligodendrocytes were treated with 7KC or << 7βOHC >> inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving [[ Mcl-1 ]], and caspase-3 activation. Question: what is the relation? Answer: activator << Cetrorelix >> completely blocked the rise of levels of the two most abundant species, 5.0 kb and 4.5 kb, of the [[ GnRH-R ]] mRNA, during both the infantile and the juvenile periods. Question: what is the relation? Answer: indirect-downregulator Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ([[ NOS ]]) and cytosolic arginase I and mitochondrial arginase II. Question: what is the relation? Answer: product-of Monocarboxylate transporters (<< MCTs >>) are proton-linked membrane carriers involved in the transport of [[ monocarboxylates ]] such as lactate, pyruvate, as well as ketone bodies. Question: what is the relation? Answer: substrate However, a lower concentration of << dipyridamole >> (3 microM) that blocks PDE9, [[ PDE10 ]], and PDE11, but not PDE8, did not inhibit ecto-phosphodiesterase activity. Question: what is the relation? Answer: inhibitor CONCLUSIONS: These findings confirm that the << CRF(1) receptor >> antagonist [[ SSR125543 ]] is able to attenuate the behavioral effects of traumatic stress exposure and indicate that these effects are associated with a normalization of hippocampal neuronal excitability impaired by stress. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 383,"Question: What is the relation in the sentence ""The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), << nuclear factor kappa B >> (NF-κB) genes expression in [[ cisplatin ]] injected rats.""? indirect-downregulator Question: What is the relation in the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]].""? upregulator Question: What is the relation in the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons.""? agonist-activator Question: What is the relation in the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and << midazolam >> (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively.""? activator Question: What is the relation in the sentence ""The potency of the selective alpha 1D-adrenoceptor antagonist BMY 7378 against noradrenaline (pA2 = 6.16 +/- 0.13) and of the selective << alpha 1A-adrenoceptor >> antagonist [[ RS-17053 ]] against noradrenaline (pKB = 8.35 +/- 0.10) and against the selective alpha 1A-adrenoceptor agonist A-61603 (pKB = 8.40 +/- 0.09) were too low to account for alpha 1D- and alpha 1A-adrenoceptor involvement.""? antagonist Question: What is the relation in the sentence ""The frdA gene coding for subunit A of FRD, and two control genes, copA and << copP >> associated with the export of [[ copper ]] out of H. pylori, were inactivated by insertion of the chloramphenicol acetyltransferase cassette into these individual genes.""? substrate Question: What is the relation in the sentence ""<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma [[ insulin ]].""? indirect-upregulator Question: What is the relation in the sentence ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the << singlet oxygen >> (1O2) donor chloramine T (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin.""? downregulator Question: What is the relation in the sentence ""BACKGROUND: Since the introduction of the first << cholinesterase >> inhibitor (ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, [[ galantamine ]] and rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase.""? inhibitor Question: What is the relation in the sentence ""Licofelone almost abolished << 5-LOX >> activity by inhibiting leukotriene B4 generation in rabbit neutrophils and prevented platelet [[ thromboxane B2 ]] production from whole blood.""? product-of Question: What is the relation in the sentence ""OBJECTIVE: Preclinical evaluation of << DRF 2655 >>, a peroxisome proliferator-activated receptor alpha (PPARalpha) and [[ PPARgamma ]] agonist, as a body-weight lowering, hypolipidemic and euglycemic agent.""? agonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""This process was reduced by a protonophore, carbonylcyanide p-trifluoromethoxyphenylhydrazone, and a typical << monocarboxylate transporter >> (MCT) inhibitor, [[ alpha-cyano-4-hydroxycinnamic acid ]], suggesting that nicotinate uptake by rat astrocytes is mediated by H(+)-coupled monocarboxylate transport system.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 384,"Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic [[ arginase I ]] and mitochondrial arginase II. Query: What is the relation? product-of It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a [[ BRCA2 ]] mutation. Query: What is the relation? downregulator Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using dexamethasone 21-phosphate (DEX-P) and [[ midazolam ]] (MDZ) as an inducer and a substrate to CYP3A, respectively. Query: What is the relation? substrate These nonadrenoceptor binding sites may explain certain novel platelet aggregatory properties previously ascribed to << clonidine >> and endogenous clonidine-displacing substance(s), and may serve as markers of [[ imidazoline receptors ]] in humans. Query: What is the relation? upregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor << Pranlukast >>, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from [[ leukotriene receptor ]] antagonism. Query: What is the relation? antagonist To determine whether H(2)S itself provoked inflammation in acinar cells, the cells were treated with H(2)S donor drug, sodium hydrosulphide (<< NaHS >>), (10, 50 and 100 muM), that resulted in a significant increase in SP concentration and expression of [[ PPT-A ]] and NK1-R in acinar cells. Query: What is the relation? indirect-upregulator The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Query: What is the relation? agonist << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Exogenous << C2-ceramide >> activates [[ c-fos serum response element ]] via Rac-dependent signalling pathway. Query: What is the relation? activator The results suggest that the 63-kDa (<< PDE 1B1 >>) and 60-kDa (PDE 1A2) CaMPDE isozymes are inhibited by felodipine and [[ nicardipine ]] by partial competitive inhibition and that these two Ca2+ antagonists appear to counteract each other. Query: What is the relation? inhibitor Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/[[ GSK-3β ]] signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc. Query: What is the relation? indirect-downregulator The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Query: What is the relation? agonist-activator Furthermore, the enzymatic activity of << alanine aminotransferase >> (ALT), which converts the critical gluconeogenic amino acid alanine into [[ pyruvate ]], is decreased (approximately 50%) in KLF15-/- hepatocytes. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 385,"Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(WAF1/<< CIP1 >>) and upregulation of cyclinB1, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2. what is the relation? indirect-upregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of Thus, << sorafenib >> may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and [[ Kit ]] signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling). what is the relation? indirect-downregulator << All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]]. what is the relation? upregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. what is the relation? agonist-activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor Lineweaver-Burk plots demonstrated that << baicalin >> inhibited the activities of [[ CYP2D ]] and CYP3A in a non-competitive manner in rat liver microsomes (RLMs). what is the relation? inhibitor Prazosin (nonselective << alpha(1)-adrenoceptor >> antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively). what is the relation? agonist Of the << PDE >> inhibitors tested, dipyridamole was most effective, with IC50 values of 1.2 and 0.45 microM for inhibition of cAMP and [[ cGMP ]] hydrolysis, respectively. what is the relation? substrate In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of AMP to << adenosine >> by [[ ecto-5'-nucleotidase ]]. what is the relation? product-of Terfenadine and << astemizole >> are chemically unrelated to [[ histamine H1-receptor ]] antagonists such as diphenhydramine and chlorpheniramine. what is the relation? antagonist These results suggest that prostacyclin may play a role in downregulating << tissue factor >> expression in monocytes, at least in part via elevation of intracellular levels of [[ cyclic AMP ]]. what is the relation? downregulator Activation of endogenous somatostatin receptor subtype 2 (sst2) by somatostatin-14 or activation of transiently transfected rat D2 dopamine receptors (<< rD2 >>(long)) by [[ quinpirole ]] had no effect. what is the relation? activator The << sibutramine >> group showed significant retardation in gastric emptying of solids (P = .03), reduced maximum tolerated volume (P = .03), and increased postprandial [[ peptide YY ]] compared with the placebo group. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 386,"Regarding ""Carnitine acetyltransferases (<< CrAT >>) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", can you determine the relation? substrate Regarding ""In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of AMP to << adenosine >> by [[ ecto-5'-nucleotidase ]]."", can you determine the relation? product-of Regarding ""The studies with dThyd rescue from cyclin E-cdk2 protein overexpression and growth inhibition by << Tomudex >> indicate that increased cyclin E-[[ cdk2 ]] protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance."", can you determine the relation? indirect-upregulator Regarding ""No effects were observed when << fenclozic acid >> was assessed for P450-dependent and P450-independent cytotoxicity to THLE cell lines, time-dependent inhibition of five major human cytochrome P450 enzymes, inhibition of the biliary [[ efflux transporters ]] BSEP and MRP2 or mitochondrial toxicity to THLE or HepG2 cells."", can you determine the relation? inhibitor Regarding ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", can you determine the relation? agonist-activator Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", can you determine the relation? substrate_product-of Regarding ""To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance."", can you determine the relation? upregulator Regarding ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of [[ VEGF ]]and MMP-9, resulting from the inhibition of Akt pathway."", can you determine the relation? downregulator Regarding ""Thus, in 158N cells, the ability of << oxysterols >> to trigger a mode of cell death by apoptosis involving [[ GSK-3 ]] and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains."", can you determine the relation? activator Regarding ""In Alexander cells, only when they were transfected with FXR+RXR, << GW4064 >> caused up-regulation of SHP and OSTβ, and a down-regulation of [[ CYP27A1 ]]."", can you determine the relation? indirect-downregulator Regarding ""Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>levobunolol approximately [[ carteolol ]]>/=timolol>atenolol."", can you determine the relation? antagonist Regarding ""Unlike the sedative hypnotics that target GABA(A) receptor complexes, << ramelteon >> is a chronohypnotic that acts on the melatonin [[ MT(1) ]] and MT(2) receptors, which are primarily located in the suprachiasmatic nucleus, the body's ""master clock."" As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades."", can you determine the relation? agonist Regarding ""Pranlukast hydrate (ONO-1078, 100 microM) downregulated the << leukotriene D(4) >>-induced [[ MUC2/5AC ]] gene expression and mucin secretion."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 387,"<< Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of [[ spermidine ]] and spermine triggers export or degradation. Please explain the relation. substrate << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of Separate << 5-aza-2'-deoxycytidine >> pretreatment or in combination with trichostatin A reduced (m)CpG and specific small interference RNAs targeting Mecp2 and [[ Creb1 ]] separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells. Please explain the relation. indirect-downregulator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]]. Please explain the relation. upregulator It is concluded that << D-1997 >> contracts the canine basilar artery by stimulating [[ 5-HT1-like receptors ]] unrelated to either the 5-HT1A or 5-HT1B receptor subtypes. Please explain the relation. activator Furthermore, V(5+) significantly inhibited the << TCDD >>-induced [[ AhR ]]-dependent luciferase activity. Please explain the relation. indirect-upregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator Like other << NMDA receptor >> antagonists, [[ memantine ]] at high concentrations can inhibit mechanisms of synaptic plasticity that are believed to underlie learning and memory. Please explain the relation. antagonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity. Please explain the relation. agonist CPT I (<< carnitine palmitoyltransferase I >>) catalyses the conversion of palmitoyl-CoA into [[ palmitoylcarnitine ]] in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria. Please explain the relation. product-of RESULTS: Following administration of the highest of the << GAL >> doses used (2.5; 5; 10 mg/kg i.m.), [[ AChE ]] activity decreased mainly in the frontal cortex, hippocampus and hypophysis. Please explain the relation. inhibitor RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against [[ COX-2 ]] (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM). Please explain the relation. downregulator The << 15-lipoxygenase >> was similarly inhibited by [[ triclosan ]] with an IC-50 of 61 microM. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 388,"Given the text ""Previous studies demonstrated that the << Group III mGlu receptor >>-selective orthosteric agonist, [[ LSP1-2111 ]] produced anxiolytic- but not antidepressant-like effects upon peripheral administration."", describe the relation. agonist Given the text ""The mechanism of action of << Fc11a-2 >> was related to the inhibition of the cleavage of pro-caspase-1, pro-IL-1β and [[ pro-IL-18 ]] which in turn suppressed the activation of NLRP3 inflammasome."", describe the relation. indirect-downregulator Given the text ""<< DBDCT >> up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of Bax/[[ Bcl-2 ]]."", describe the relation. indirect-upregulator Given the text ""AIM: To assess the efficacy and safety of a 24-week treatment with << sitagliptin >>, a highly selective once-daily oral [[ dipeptidyl peptidase-4 ]] (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and >, a principal product of [[ phospholipase A2 ]], was rapidly induced by the addition of C2-ceramide in a Rac-dependent manner."", describe the relation. product-of Given the text ""Taken together, our results suggested that << Rg1 >> protected against Aβ25-35-induced apoptosis at least in part by two complementary GR-dependent [[ ERK ]] phosphorylation pathways: (1) down-regulating HIF-1α initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades."", describe the relation. activator Given the text ""To determine whether << 3,4-methylenedioxymethamphetamine >> (MDMA)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured."", describe the relation. downregulator Given the text ""These protective effects were abolished by glucocorticoid receptor (<< GR >>) antagonist [[ RU486 ]] or p-ERK inhibitor U0126 rather than estrogen receptor α antagonist ICI 82,780."", describe the relation. antagonist Given the text ""The enzyme << dimethylarginine dimethylaminohydrolase >> (DDAH) specifically hydrolyzes these asymmetrically methylated [[ arginine ]] residues to citrulline and methylamines."", describe the relation. substrate Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]]."", describe the relation. upregulator Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""Using << hNET >> in transfected human embryonic kidney-293 cells, this difference in potency for DVS at sites labeled by [(3)H]NIS was found to distinguish DVS, the DVS analog [[ rac-(1-[1-(3-chloro-phenyl)-2-(4-methylpiperazin-1-yl)-ethyl]cyclohexanol ]] (WY-46824), methylphenidate, and the cocaine analog 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester (RTI-55) from other hNET antagonists, such as NIS, mazindol, tricyclic antidepressants, and cocaine."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 389,"Given the text ""UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and << UDP >>-glucuronic acid than the other [[ UGTs ]]."", describe the relation. substrate Given the text ""Furthermore, << BRN-250 >> inhibited the [[ VEGF ]]-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream AKT pathway."", describe the relation. inhibitor Given the text ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent << amino acid >> transporter, with functional features of [[ ASCT2 ]] transport."", describe the relation. upregulator Given the text ""<< Agmatine >>, locally synthesized, is an endogenous agonist at [[ imidazoline receptors ]], a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter."", describe the relation. agonist Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals."", describe the relation. antagonist Given the text ""The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of [[ nuclear factor-κB ]] (NF-κB) p65 and p50 subunits."", describe the relation. indirect-downregulator Given the text ""Furthermore, compared with control groups, the plaque endothelium level of p75(NTR) was 3-fold increased and the liver level of << p75(NTR) >> was 17.4-fold increased by [[ SFO ]]-HD."", describe the relation. indirect-upregulator Given the text ""Ferredoxin 1 (<< FDX1 >>; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues."", describe the relation. product-of Given the text ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase ([[ GPx ]]) activities, while increased catalase (CAT) activity compared with the control."", describe the relation. downregulator Given the text ""Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to << NRF2 >> inducers ([[ sulforaphane ]], tert-butylhydroquinone, cinnamic aldehyde, and hydrogen peroxide) showed that the aldo-keto reductase (AKR) 1C1 is highly inducible by all treatments."", describe the relation. activator Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""We show that the binding of thalidomide photoaffinity label to authentic human AGP is competed with both << thalidomide >> and the nonradioactive photoaffinity label at concentrations comparable to those required for inhibition of production of [[ tumor necrosis factor alpha ]] from human monocytes, suggesting that AGP may be involved in the immunomodulatory activity of thalidomide."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 390,"Regarding ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."", can you determine the relation? agonist Regarding ""<< Aldosterone >> also induces the rapid phosphorylation of Protein Kinase D1 ([[ PKD1 ]])."", can you determine the relation? activator Regarding ""Dopamine D(2) receptor-induced << COX-2 >>-mediated production of [[ prostaglandin E(2) ]] in D(2)-transfected Chinese hamster ovary cells without simultaneous administration of a Ca(2+)-mobilizing agent."", can you determine the relation? substrate Regarding ""<< Alprenolol >> and bromoacetylalprenololmenthane are competitive slowly reversible antagonists at the [[ beta 1-adrenoceptors ]] of rat left atria."", can you determine the relation? antagonist Regarding ""Treatment with << carvedilol >> is associated with a reversal of abnormal regulation of [[ HIF-1alpha ]] and VEGF in the failing ventricular myocardium."", can you determine the relation? indirect-downregulator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", can you determine the relation? agonist-activator Regarding ""<< 5-Fluorouracil >> (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of [[ thymidylate synthase ]] (TS)."", can you determine the relation? inhibitor Regarding ""BACKGROUND AND AIMS: << Glutamic acid decarboxylase >> (GAD, EC 4.1.1.15) catalyses the conversion of glutamate to [[ gamma-aminobutyric acid ]] (GABA)."", can you determine the relation? product-of Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""<< All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]]."", can you determine the relation? upregulator Regarding ""However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]]."", can you determine the relation? indirect-upregulator Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of VEGF and [[ MMP-9 ]] through Akt pathway in MDA-MB-231 breast cancer cells."", can you determine the relation? downregulator Regarding ""Ex vivo, lumiracoxib inhibited << COX-1 >>-derived thromboxane B(2) ([[ TxB(2) ]]) generation with an ID(50) of 33 mg kg(-1), whereas COX-2-derived production of prostaglandin E(2) (PGE(2)) in the lipopolysaccharide-stimulated rat air pouch was inhibited with an ID(50) value of 0.24 mg kg(-1)."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 391,"<< Cortisol >> and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial [[ PTGS2 ]] activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium. Please explain the relation. activator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor << Doxorubicin >> is mainly excreted into the bile via [[ P-glycoprotein ]] (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily. Please explain the relation. substrate In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the << PGE1 >> mediated stimulation of [[ Na,K-ATPase beta ]] subunit gene transcription includes the stimulatory effect of 17-phenyl trinor PGE2, as well as the inhibitory effects of SC-51089. Please explain the relation. indirect-upregulator Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (ramelteon, << TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice. Please explain the relation. agonist Western blotting demonstrated that << DMBT >> effectively suppressed the expression of VEGF, [[ p-VEGFR-2 ]], p-EGFR, and p-Akt. Please explain the relation. indirect-downregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to << AMP >> by ecto-[[ phosphodiesterase ]], and metabolism of AMP to adenosine by ecto-5'-nucleotidase. Please explain the relation. product-of << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Please explain the relation. substrate_product-of At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of GluN1/[[ GluN2B ]] receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic. Please explain the relation. downregulator Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats. Please explain the relation. upregulator A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, << caffeic acid >>, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]). Please explain the relation. inhibitor The isoprenaline attenuation responses of the portal vein were inhibited by labetalol and dilevalol (both at > or = 10(-7) M) and the pA2 value for the << labetalol >> at [[ beta 2-adrenoceptors ]] was 7.59. Please explain the relation. antagonist CONCLUSIONS: << Aspirin >> is an inhibitor of [[ mTOR ]] and an activator of AMPK, targeting regulators of intracellular energy homeostasis and metabolism. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 392,"Regarding ""Expression of the dominant negative mutants rab5A-N133I or << rab7 >>-N125I blunted [[ U50,488H ]]-induced down-regulation."", can you determine the relation? downregulator Regarding ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively."", can you determine the relation? activator Regarding ""These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by SP-[[ NK-1R ]] related pathway in mouse pancreatic acinar cells."", can you determine the relation? product-of Regarding ""OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of << FADS2 >> affects the PUFA biosynthetic pathway and consequently modifies the effect of [[ alpha-linolenic acid ]] (ALA) on myocardial infarction (MI)."", can you determine the relation? substrate Regarding ""alpha(1)-Adrenoceptor antagonists were tested against the << phenylephrine >> ([[ alpha(1)-adrenoceptor ]] agonist)-induced contraction in isolated hamster ureteral preparations using a functional experimental approach."", can you determine the relation? agonist Regarding ""<< Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ [[ glycogen synthase kinase 3β ]] (GSK-3β) signaling pathway."", can you determine the relation? indirect-downregulator Regarding ""Indomethacin inhibited both hCOX-1 and hCOX-2, whereas << NS-398 >> and Dup-697 selectively inhibited [[ hCOX-2 ]]."", can you determine the relation? inhibitor Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""In the liver of rats given << flutamide >> as initiating agent at the dose of 500 mg/kg/week for 6 successive weeks, [[ gamma-glutamyltraspeptidase ]]-positive foci were detected only in 3 of 10 rats."", can you determine the relation? indirect-upregulator Regarding ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", can you determine the relation? agonist-activator Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""<< EP(1) >> and EP(3) receptor antagonists [[ ONO-8713 ]] and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."", can you determine the relation? antagonist Regarding ""<< CYP1A1 >> and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", can you determine the relation? upregulator Regarding ""<< Mn >> (10 and 20 mg/kg) increased [[ caspase ]] activity and F(2)-isoprostane production (a biological marker of lipid peroxidation)."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 393,"Given the text ""<< S1P >> increased the amount of [[ osteoprotegerin ]] at both mRNA and protein levels, and increased the activity of alkaline phosphatase, leading to the mineralization."", describe the relation. indirect-upregulator Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""[Pharmacological effects of a << mu-opioid receptor >> antagonist [[ naltrexone ]] on alcohol dependence]."", describe the relation. antagonist Given the text ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", describe the relation. agonist-activator Given the text ""However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of [[ metallothionein-II ]] production, and an increase in p53 activation and the pro-apoptotic protein Bax."", describe the relation. downregulator Given the text ""These findings demonstrate that << PEPT2 >> is the primary transporter responsible for [[ cefadroxil ]] uptake in the choroid plexus."", describe the relation. substrate Given the text ""Depletion of putrescine, spermidine, and spermine by << DL-alpha-difluoromethylornithine >> (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index."", describe the relation. inhibitor Given the text ""<< Aldosterone >> also induces the rapid phosphorylation of [[ Protein Kinase D1 ]] (PKD1)."", describe the relation. activator Given the text ""Alprenolol and BAAM also caused surmountable antagonism of << isoprenaline >> responses, and this [[ beta 1-adrenoceptor ]] antagonism was slowly reversible."", describe the relation. agonist Given the text ""Western blotting demonstrated that << DMBT >> effectively suppressed the expression of VEGF, [[ p-VEGFR-2 ]], p-EGFR, and p-Akt."", describe the relation. indirect-downregulator Given the text ""On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]]."", describe the relation. upregulator Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from << xanthine oxidase >>-generated [[ superoxide ]] and NO."", describe the relation. product-of Given the text ""Herein, we report the identification and characterization of 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile (ESI-09), a novel noncyclic << nucleotide >> EPAC antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated [[ insulin ]] secretion in pancreatic β cells."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 394,"Consider the text ""N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase (<< EC 3.1.4.45 >>; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome."". Can you identify the relation? product-of Consider the text ""Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity."". Can you identify the relation? upregulator Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""Furthermore, << BRN-250 >> inhibited the [[ VEGF ]]-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream AKT pathway."". Can you identify the relation? inhibitor Consider the text ""Expression of the dominant negative mutants rab5A-N133I or << rab7 >>-N125I blunted [[ U50,488H ]]-induced down-regulation."". Can you identify the relation? downregulator Consider the text ""Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the << dopamine D1 receptor >> antagonist SCH 39166 ([[ (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine ]]) and the dopamine D2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg)."". Can you identify the relation? antagonist Consider the text ""Cotreatment with << U0126 >> and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, JNK, and [[ beta-catenin ]]."". Can you identify the relation? indirect-downregulator Consider the text ""The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and [[ AH 6809 ]] (EP1 and EP2 specific)."". Can you identify the relation? agonist Consider the text ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal << cytochrome P450 3A >> (CYP3A) in rats using dexamethasone 21-phosphate ([[ DEX-P ]]) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively."". Can you identify the relation? activator Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the << chenodeoxycholic acid >> (CDCA)-induced expression of Cdx2 and [[ MUC2 ]] in normal rat gastric epithelial cells (RGM-1 cells)."". Can you identify the relation? indirect-upregulator Consider the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""The << mitochondrial respiratory chain complex IV >> (cytochrome c oxidase) is a multi-subunit enzyme that transfers electrons from cytochrome c to molecular [[ oxygen ]], yielding water."". Can you identify the relation? substrate Consider the text ""CO treatment also inhibited LPS-induced << NO >> production and [[ iNOS ]] expression via its inactivation of NF-kappaB."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 395,"Given the text ""In contrast, the << D-1997 >>-induced responses were potently and concentration-dependently antagonized by the mixed 5-HT1-like and [[ 5-HT2 receptor ]] antagonist methiothepin (0.01-1 microM)."", describe the relation. agonist Given the text ""To further our understanding of how << fisetin >> negatively regulates [[ mTORC1 ]] signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells."", describe the relation. downregulator Given the text ""Brain tissue analyses revealed that neonatal quinpirole treatment produced a significant decrease in hippocampal NGF, << BDNF >> and ChAT that was eliminated by [[ olanzapine ]] treatment."", describe the relation. indirect-upregulator Given the text ""In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of << serotonin >> with transport-ready conformations of [[ SERT ]] when concentrations of serotonin were low and rate limiting."", describe the relation. substrate Given the text ""The upregulation of << calpain >>, tBid and caspase-3 activity were further inhibited by treatment with [[ EGTA ]] in the presence of ALD."", describe the relation. indirect-downregulator Given the text ""<< Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity."", describe the relation. upregulator Given the text ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", describe the relation. agonist-activator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""Taken together, our findings indicate that << 5HHMF >> suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of [[ Nrf2 ]]-dependent HO-1 activity."", describe the relation. activator Given the text ""<< Tolbutamide >> and gliclazide block the K(ATP) channel K(ir)6.2/[[ Sur1 ]], causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells."", describe the relation. inhibitor Given the text ""These results indicate transcription of << FDX1 >> is regulated by the NR5A family and cAMP signaling, and participates in [[ steroid ]] hormone production in ovarian granulosa cells."", describe the relation. product-of Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""Since the original discovery of << azoles >> analogs as PXR antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic [[ PXR ]] antagonists."", describe the relation. antagonist Given the text ""L-arg is converted to << urea >> by [[ arginase I ]] in the liver and arginase II in the kidney."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 396,"The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Question: what is the relation? Answer: agonist Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, << tert-butylhydroquinone >>, cinnamic aldehyde, and hydrogen peroxide) showed that the [[ aldo-keto reductase (AKR) 1C1 ]] is highly inducible by all treatments. Question: what is the relation? Answer: indirect-upregulator 3.  We have used this method to screen 11 recombinant << human UGTs >> for [[ HFC ]] glucuronidation activity and studied the reaction kinetics with the most active enzymes. Question: what is the relation? Answer: substrate In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and [[ MBD-3 ]]), in MEF cells by the proteasomal pathway. Question: what is the relation? Answer: downregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Question: what is the relation? Answer: agonist-activator In the present study, we compared the pharmacology of (+/-)pindolol, WAY-100635 (a 5-HT(1A) antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and << isamoltane >> (a [[ 5-HT(1B) ]] antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. Question: what is the relation? Answer: antagonist As add-on therapy in patients with suboptimal glycaemic control despite oral antihyperglycaemic treatment, sitagliptin improved << HbA(1c) >> to a significantly greater extent than placebo when added to metformin or pioglitazone and was noninferior to glipizide when added to [[ metformin ]]. Question: what is the relation? Answer: indirect-downregulator First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (<< ABCA1 >>)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner. Question: what is the relation? Answer: product-of Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Question: what is the relation? Answer: substrate_product-of Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration. Question: what is the relation? Answer: upregulator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and << aniline 4-hydroxylase >> activity and cytochrome P450, compared to the [[ CCl4 ]] only group. Question: what is the relation? Answer: activator Repression of << farnesyltransferase >> (FNTA) by siRNA and the enzyme inhibitor [[ manumycin A ]] caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. Question: what is the relation? Answer: inhibitor In conclusion, our data suggest that chronic << cocaine >> use is associated with modestly reduced levels of striatal DA and the [[ DA transporter ]] in some subjects and that these changes might contribute to the neurological and psychiatric effects of the drug. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 397,"Effect of << ramelteon >> (TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor performance in mice. what is the relation? agonist Treatment of Rat-2 fibroblast cells with << C2-ceramide >> caused the stimulation of [[ c-fos SRE ]]-dependent reporter gene activity in a dose- and time-dependent manner by transient transfection analysis. what is the relation? activator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. what is the relation? agonist-activator Both NS-398 and Dup-697 exhibited time-dependent inactivation of << hCOX-2 >>, as did [[ indomethacin ]] on both enzymes. what is the relation? inhibitor Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>[[ atenolol ]]. what is the relation? antagonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in [[ MSG ]]-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). what is the relation? downregulator << Methionine synthase reductase >> (MTRR) is an enzyme involved in the conversion of [[ Hcy ]] to methionine. what is the relation? substrate There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant << p53 >> protein expression in the [[ parathion ]]-treated cells. what is the relation? indirect-upregulator PIP5K1B encodes << phosphatidylinositol 4-phosphate 5-kinase β type I >> (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate [[ phosphatidylinositol-4,5-bisphosphate ]] [PI(4,5)P2]. what is the relation? product-of On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]]. what is the relation? upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. what is the relation? agonist-inhibitor << Genistin >> decreased [[ myosin light chain kinase ]] (MLCK) protein contents and MLCK mRNA expression in IJS, and inhibited both phosphorylation and Mg(2+)-ATPase activity of purified myosin, implicating that the decrease of MLCK contents and inhibition of MLCK activity are involved in the genistin-induced inhibitory effects. what is the relation? indirect-downregulator Targeted disruption of the gene encoding the N-glycosyltransferase, prlH, abolished pyralomicin production, and recombinant expression of PrlA confirms the activity of this enzyme as a << sugar phosphate cyclase >> involved in the formation of the [[ C7 ]]-cyclitol moiety. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 398,"<< Acetazolamide >>, a specific inhibitor of [[ CA ]], reduces the activity of CA I and CA II from red cells. Query: What is the relation? inhibitor << I3A >> induced a higher level of secretion of the inflammatory [[ cytokine ]] interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction. Query: What is the relation? indirect-upregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of alpha-Tocopherol transfer protein (<< alpha-TTP >>), the product of the gene responsible for familial isolated vitamin E deficiency, plays an important role in maintaining the plasma [[ alpha-tocopherol ]] level by mediating the secretion of alpha-tocopherol by the liver. Query: What is the relation? substrate Furthermore, treatment with << spironoclactone >> not only attenuated the pro-apoptotic effect of ALD but reversed the ALD-induced increase of calpain and [[ AIF ]] levels. Query: What is the relation? indirect-downregulator Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512). Query: What is the relation? upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Query: What is the relation? agonist-inhibitor Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM << 2,3,7,8-tetrachlorodibenzodioxin >> (TCDD), the most potent activator of [[ AhR ]]. Query: What is the relation? activator Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, prazosin, tamsulosin and [[ terazosin ]]) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials. Query: What is the relation? antagonist The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists << SC-51089 >> (EP1 specific) and AH 6809 ([[ EP1 ]] and EP2 specific). Query: What is the relation? agonist We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase ([[ CHS ]]), and an antioxidant enzyme such as ascorbate peroxidase (APX). Query: What is the relation? product-of The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator These results suggest that prostacyclin may play a role in downregulating << tissue factor >> expression in monocytes, at least in part via elevation of intracellular levels of [[ cyclic AMP ]]. Query: What is the relation? downregulator Using this assay, we found that both << superoxide >> and nitric oxide inhibit renal cortical [[ DDAH ]] activity in vitro. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 399,"In contrast, the selective << beta2AR >> antagonists [[ ICI-118,551 ]] and butoxamine inhibited isoproterenol-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively). Question: what is the relation? Answer: antagonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor << P2Y(2) receptor >> agonist [[ INS37217 ]] enhances functional recovery after detachment caused by subretinal injection in normal and rds mice. Question: what is the relation? Answer: agonist db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively. Question: what is the relation? Answer: upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Question: what is the relation? Answer: agonist-activator Ferredoxin 1 (FDX1; << adrenodoxin >>) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues. Question: what is the relation? Answer: product-of << OMT >> showed partial protection in the cortical neurons via down-regulation of NR2B containing [[ NMDA receptors ]] and up-regulation of Bcl-2 family. Question: what is the relation? Answer: downregulator A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, << syringic acid >>, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme [[ carbonic anhydrase ]] (CA, EC 4.2.1.1). Question: what is the relation? Answer: inhibitor Since << gemfibrozil >> is known to activate peroxisome proliferator-activated receptor-alpha ([[ PPAR-alpha ]]), we investigated the role of PPAR-alpha in gemfibrozil-mediated inhibition of iNOS. Question: what is the relation? Answer: activator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Question: what is the relation? Answer: substrate_product-of Firstly, in the normal human renal epithelial HK-2 cells, the measurement of the expression of 30 previously reported NRF2 target genes in response to NRF2 inducers (sulforaphane, tert-butylhydroquinone, << cinnamic aldehyde >>, and hydrogen peroxide) showed that the [[ aldo-keto reductase (AKR) 1C1 ]] is highly inducible by all treatments. Question: what is the relation? Answer: indirect-upregulator The mRNA levels of << microphthalmia-associated transcription factor >> (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment. Question: what is the relation? Answer: indirect-downregulator We examined the N-demethylation of individual << ketamine >> enantiomers using human liver microsomes (HLMs) genotyped for the [[ CYP2B6*6 ]] allele, insect cell expressed recombinant CYP2B6 and CYP3A4 enzymes and COS-1 cell expressed recombinant CYP2B6.1 and CYP2B6.6 protein variant. Question: what is the relation? Answer: substrate In the presence of IL-18, << simvastatin >> suppressed the expression of ICAM-1 and CD40 as well as the production of [[ IL-12 ]], TNF-alpha and IFN-gamma in PBMC, contributing to the anti-inflammatory effect of simvastatin. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 400,"In reference to ""We found that << PSE >> inhibits interleukin-2 ([[ IL-2 ]]) and tumor necrosis factor (TNF) alpha-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line."", what is the relation? indirect-downregulator In reference to ""<< Terfenadine >> and astemizole are chemically unrelated to [[ histamine H1-receptor ]] antagonists such as diphenhydramine and chlorpheniramine."", what is the relation? antagonist In reference to ""Unlike the sedative hypnotics that target GABA(A) receptor complexes, << ramelteon >> is a chronohypnotic that acts on the melatonin MT(1) and [[ MT(2) ]] receptors, which are primarily located in the suprachiasmatic nucleus, the body's ""master clock."" As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades."", what is the relation? agonist In reference to ""In ex vivo experiments with tumor cells from refractory chronic lymphoblastic leukemia, dose-dependent << CDK2 >> inhibition associated with apoptotic changes was seen at concentrations greater than 100 nM of [[ flavopiridol ]]."", what is the relation? inhibitor In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Thus, it can be suggested that the inhibitory action of ginseng saponins against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking << norepinephrine >>- and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage rather than in the brain."", what is the relation? indirect-upregulator In reference to ""<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase ([[ AADC ]]) and catechol-O-methyltransferase (COMT)."", what is the relation? substrate In reference to ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""To begin to examine whether these changes are mediated by alterations in gene expression for << tryptophan hydroxylase >> (TPH), the rate-limiting enzyme in [[ 5-HT ]] biosynthesis, we quantitated its mRNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR)."", what is the relation? product-of In reference to ""Activation of << alpha 2B-adrenoceptors >> mediates the cardiovascular effects of [[ etomidate ]]."", what is the relation? activator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""<< Statins >> increase p21 through inhibition of histone deacetylase activity and release of promoter-associated [[ HDAC1/2 ]]."", what is the relation? upregulator In reference to ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."", what is the relation? downregulator In reference to ""KEY RESULTS: Several agonists were found to be highly subtype selective because of selective affinity (e.g. salmeterol and formoterol, for the beta(2)-adrenoceptor over the << beta(1) >> or beta(3)), while others (e.g. [[ isoprenaline ]]) had little affinity-selectivity."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 401,"The above results indicate that polyamine depletion delays the onset of apoptosis in IEC-6 cells and confers protection against DNA damaging agents, suggesting that << polyamines >> might be involved in the [[ caspase ]] activating signal cascade. Please explain the relation. indirect-upregulator CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme. Please explain the relation. upregulator Discovery of novel << 2-hydroxydiarylamide >> derivatives as [[ TMPRSS4 ]] inhibitors. Please explain the relation. inhibitor << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein ([[ pRb ]]), and the upregulation of p21(WAF1/CIP1) and p53. Please explain the relation. downregulator The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure. Please explain the relation. agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of << Phenytoin >> is principally metabolized by CYP2C9, and both are probable substrates of the [[ drug transporter ]] P-glycoprotein. Please explain the relation. substrate Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Please explain the relation. agonist-activator << 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to [[ TSC2 ]]. Please explain the relation. activator The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (<< lorglumide >>, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini. Please explain the relation. antagonist However, whether increasing << EETs >> production by [[ CYP2J2 ]] overexpression in vivo could prevent abdominal aortic aneurysm (AAA) remains unknown. Please explain the relation. product-of In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), [[ lactic dehydrogenase ]] (LDH), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system. Please explain the relation. indirect-downregulator Inhibition of Th1/Th17 responses via suppression of STAT1 and << STAT3 >> activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside [[ icariin ]]. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 402,"RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Please explain the relation. agonist-activator However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an N-methyl d-aspartate receptor ([[ NMDAR ]]) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting. Please explain the relation. antagonist Crocin (25 and 50mg/kg) or << vitamin E >> improved histopathological damages, decreased MDA and [[ CK-MB ]], increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. Please explain the relation. indirect-downregulator Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal << cytochrome P450 3A >> (CYP3A) in rats using dexamethasone 21-phosphate ([[ DEX-P ]]) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively. Please explain the relation. activator Third, << ABCA1 >>-RNAi suppressed hepatic [[ alpha-tocopherol ]] secretion. Please explain the relation. product-of The purified << phosphodiester alpha-GlcNAcase >> has a specific activity of 498 micromol of [3H]GlcNAc-alpha-phosphomannose-alpha-methyl cleaved per h per mg of protein using 0.5 mM [[ [3H]GlcNAc-alpha-phosphomannose-alpha-methyl ]] as substrate. Please explain the relation. substrate Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor << Epi >> increased both [[ WNT6 ]]/Wnt6 and Cav1 expression in human GC cells and within the tumor area of a murine model of GC (CEA424-SV40 TAg). Please explain the relation. indirect-upregulator Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.). Please explain the relation. upregulator In combination with << clofarabine >>, the ability of resveratrol to reduce the contents of [[ Sp1 ]] and its target gene products was also evident in a time- and dose-dependent experiment. Please explain the relation. downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and << ellagic acid >>, were investigated for their inhibitory effects against the [[ metalloenzyme ]] carbonic anhydrase (CA, EC 4.2.1.1). Please explain the relation. inhibitor The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Please explain the relation. agonist In rats, << rifamycin SV >> and rifampicin were shown to interfere with hepatic organic anion uptake by inhibition of the [[ organic anion transporting polypeptides ]] Oatp1 and Oatp2. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 403,"Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (<< DEX-P >>) and midazolam (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively."". Can you identify the relation? substrate Consider the text ""<< U50, 488H >> caused a significant down-regulation of the [[ hkor ]], although etorphine did not."". Can you identify the relation? downregulator Consider the text ""The treatment of U937 cells with << NRF2 >> inducers including [[ sulforaphane ]] effectively elevated the expression of AKR1B1, 1B10, 1C1, 1C2, and 1C3."". Can you identify the relation? activator Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, [[ nuclear factor-kappaB ]] and activating protein-1, which were increased in fructose-fed rats."". Can you identify the relation? upregulator Consider the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""Thus, we found that << 5HHMF >> enhances heme oxygenase-1 ([[ HO-1 ]]) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation."". Can you identify the relation? indirect-upregulator Consider the text ""Nizatidine (<< LY139037 >>), a selective [[ histamine H2-receptor ]] antagonist, is a potent inhibitor of gastric acid secretion."". Can you identify the relation? antagonist Consider the text ""Both NS-398 and Dup-697 exhibited time-dependent inactivation of << hCOX-2 >>, as did [[ indomethacin ]] on both enzymes."". Can you identify the relation? inhibitor Consider the text ""The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure."". Can you identify the relation? agonist Consider the text ""<< ACTH >>-stimulated peak cortisol, [[ delta cortisol ]], and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover."". Can you identify the relation? product-of Consider the text ""<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and [[ Mcl-1 ]], leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27."". Can you identify the relation? indirect-downregulator Consider the text ""In vitro metabolism of the << 5-hydroxytryptamine1B >> receptor antagonist [[ elzasonan ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 404,"One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). what is the relation? substrate_product-of CONCLUSION: A long-term intake of ethanol solution down-regulates the phosphorylation of << CREB >> in the nucleus accumbens, and those changes can be reversed by [[ naloxone ]], which may be one kind of the molecular mechanisms associated with ethanol dependence. what is the relation? upregulator The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, [[ phospholamban ]] (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation. what is the relation? substrate Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Treatment with << diclofenac >> resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated [[ caspase-3 ]] after 6 hr, indicating that diclofenac may cause apoptosis of neuronal cells via activation of the caspase cascade. what is the relation? activator << Phillyrin >> strongly inhibited high glucose-induced fatty acid synthase ([[ FAS ]]) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation. what is the relation? indirect-downregulator The data show that CP[c]Ph is less potent at inducing << CYP1A >> gene expression in rainbow trout than [[ benzo[a]pyrene ]] (B[a]P), a well-known Ah-receptor agonist. what is the relation? indirect-upregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. what is the relation? antagonist RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. what is the relation? agonist-activator Platelet-induced << COX-2 >>-dependent [[ PGE2 ]] synthesis in HT29 cells was involved in downregulation of p21(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by rofecoxib(a selective COX-2 inhibitor) and rescued by exogenous PGE2. what is the relation? product-of << Sorafenib >> (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/[[ ERK ]] pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. what is the relation? inhibitor We previously reported that << aminoglycoside >> antibiotics reduce [[ SGLT1 ]]-dependent glucose transport in pig proximal tubular epithelial LLC-PK1 cells in parallel with the order of their nephrotoxicity. what is the relation? downregulator << Terbutaline >> (Bricanyl) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients. what is the relation? agonist Nicotinamide N-methyltransferase (<< NNMT >>) catalyses the conversion of [[ nicotinamide ]] to 1-methylnicotinamide and plays an important role in hepatic detoxification reactions. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 405,"<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Question: what is the relation? Answer: agonist-activator Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively. Question: what is the relation? Answer: activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Question: what is the relation? Answer: substrate_product-of Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Question: what is the relation? Answer: agonist-inhibitor << Ferredoxin 1 >> (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid hormone ]] synthesis in mammalian tissues. Question: what is the relation? Answer: product-of On the other hand, in patients with a mean serum carvedilol level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start of<< carvedilol >> therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l. Question: what is the relation? Answer: indirect-downregulator CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Question: what is the relation? Answer: upregulator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, [[ c-Myc ]], and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Question: what is the relation? Answer: downregulator Histamine content, HDC activity and << HDC >> mRNA expression in nasal mucosa were also significantly increased after [[ TDI ]] provocation. Question: what is the relation? Answer: indirect-upregulator We used mutagenesis of these residues, combined with an investigation of << hERG >> block by close analogs of clofilium and [[ ibutilide ]], to assess how specific alterations in drug structure affected potency and binding interactions. Question: what is the relation? Answer: inhibitor << Aldose reductase >> (AR) catalyzes the reduction of toxic lipid [[ aldehydes ]] to their alcohol products and mediates inflammatory signals triggered by lipopolysaccharide (LPS). Question: what is the relation? Answer: substrate Identification of a novel << benzimidazole >> derivative as a highly potent [[ NPY Y5 receptor ]] antagonist with an anti-obesity profile. Question: what is the relation? Answer: antagonist After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and [[ histamine ]]. Question: what is the relation? Answer: agonist << VPA >> caused a significant concentration- dependent increase in limb abnormalities, which was correlated with its [[ HDAC ]] inhibitory effect. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 406,"Furthermore, << BRN-250 >> inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of [[ VEGF receptor 2 ]] (VEGFR2) and the activation of its downstream AKT pathway. Query: What is the relation? inhibitor << All-trans retinoic acid >> protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating [[ collagen 8A2 ]]. Query: What is the relation? upregulator << Mitochondrial arginase II >> modulates nitric-oxide synthesis through nonfreely exchangeable [[ L-arginine ]] pools in human endothelial cells. Query: What is the relation? substrate Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Meanwhile, autophagy was detected as early as 12 h after an exposure to low-dose << dioscin >>, as indicated by an up-regulated expression of [[ LC3-II ]] and beclin-1 proteins. Query: What is the relation? indirect-upregulator Inhibition of binding of the alpha2-receptor antagonist << [3H]RX821002 >> to recombinant [[ alpha2-receptors ]] by etomidate was tested in human embryonic kidney (HEK293) cells in vitro. Query: What is the relation? antagonist We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as [[ l-phenylalanine ammonia-lyase ]] (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as ascorbate peroxidase (APX). Query: What is the relation? product-of Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal << cytochrome P450 3A >> (CYP3A) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively. Query: What is the relation? activator Effect of << (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide >> (ramelteon, TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice. Query: What is the relation? agonist The results suggest that the suppression of << TLR4 >> activity by auranofin may be the molecular mechanism through which [[ auranofin ]] exerts anti-rheumatic activity. Query: What is the relation? downregulator The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Thalidomide >> reduced [[ COX-2 ]] expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60. Query: What is the relation? indirect-downregulator 100 micromol/L rifampicin inhibited << OATP-C >>- and OATP8-, OATP-B- and OATP-A-mediated [[ BSP ]] uptake by 66%, 96%, 25%, and 49%, respectively. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 407,"CONCLUSIONS: Total vitamin B6 is abnormally high in autism, consistent with previous reports of an impaired << pyridoxal kinase >> for the conversion of pyridoxine and [[ pyridoxal ]] to PLP. what is the relation? substrate Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of The significantly decreased levels of p-PI3K and << p-AKT >> expression were observed in SGC-7901 cells after [[ β-ionone ]] treatments in a time- and dose-dependent manner (P < 0.01). what is the relation? indirect-downregulator In the present study, we compared the pharmacology of (+/-)pindolol, << WAY-100635 >> (a [[ 5-HT(1A) ]] antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. what is the relation? antagonist In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of << WIN 55,212 >> antagonized by the [[ CB2 ]] antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]. what is the relation? agonist As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and << xanthine oxidase >> was identified as the likely source of TES-stimulated [[ superoxide ]] production. what is the relation? product-of Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor CONCLUSIONS: Our results show that << indomethacin >>, a known cyclooxygenase (COX) inhibitor, is also an activator of [[ CA ]]. what is the relation? activator Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner. what is the relation? upregulator The hemoglobin A1c (<< HbA1c >>) of all patients improved significantly from 8.1±1.2% to 7.6±1.1% after 12 weeks of add-on therapy with [[ sitagliptin ]] (p<0.01), and the insulin dosage was reduced from 27.3±15.8 U/day to 24.5±16.5 U/day (p<0.001). what is the relation? indirect-upregulator Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]. what is the relation? downregulator Previous studies by this research team proved that vasodilating prostaglandins (<< PGs >>) E1, E2 and I2 inhibit carbonic anhydrase ([[ CA ]]) in vitro and in vivo, which suggested involvement of CA in gastric acid secretion inhibition and the increase of gastric mucosa blood flow produced by this group of PGs. what is the relation? inhibitor << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. what is the relation? agonist-activator The nonselective and irreversible << MAO >> inhibitors, phenelzine (3-10 mg/kg), [[ tranylcypromine ]] (1-3 mg/kg), and nialamide (30 mg/kg), decreased rates of responding maintained by ethanol reinforcement. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 408,"<< Gemfibrozil >>, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible nitric-oxide synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes. Please explain the relation. indirect-downregulator Pharmacological properties of << lorglumide >> as a member of a new class of [[ cholecystokinin ]] antagonists. Please explain the relation. antagonist The effects of << theophylline >> (unspecific [[ PDE ]] inhibitor), vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor) and the PDE5 inhibitors zaprinast and E 4021 were weak. Please explain the relation. inhibitor In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively. Please explain the relation. activator Specificity of << zebrafish retinol saturase >>: formation of all-trans-13,14-dihydroretinol and [[ all-trans-7,8- dihydroretinol ]]. Please explain the relation. product-of Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in [[ ERK1/2 ]] and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR. Please explain the relation. upregulator Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM [[ 2,3,7,8-tetrachlorodibenzodioxin ]] (TCDD), the most potent activator of AhR. Please explain the relation. indirect-upregulator Expression of the dominant negative mutants rab5A-<< N133I >> or rab7-N125I blunted [[ U50,488H ]]-induced down-regulation. Please explain the relation. downregulator << TAS-102 >> is a novel drug containing trifluorothymidine, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS. Please explain the relation. substrate The involvement of << EP1 >> and EP2 receptors is indicated by studies with the EP1 selective agonist [[ 17-phenyl trinor PGE2 ]], and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Please explain the relation. agonist << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator Imatinib (<< STI571 >>, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, PDGFRA, and [[ PDGFRB, ]] represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 409,"Question: What is the relation in the sentence ""We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (<< CDCA >>)-induced expression of Cdx2 and [[ MUC2 ]] in normal rat gastric epithelial cells (RGM-1 cells).""? indirect-upregulator Question: What is the relation in the sentence ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats.""? upregulator Question: What is the relation in the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Stable << ABCC1 >>, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and ABCC2 the apical excretion of [[ BPDE glutathione ]] conjugates.""? substrate Question: What is the relation in the sentence ""First, addition of << apolipoprotein A-I >> (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner.""? product-of Question: What is the relation in the sentence ""Gene expression profiling (GEP) of GIST-S, GIST-R cells and two IM resistant GIST patients demonstrated that << KIT >> is downregulated implying a major role in [[ IM ]] resistance.""? indirect-downregulator Question: What is the relation in the sentence ""5-(N,N-dimethyl)-amiloride (50 microM; << DMA >>), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not [[ NHE3 ]], did not affect DBS.""? inhibitor Question: What is the relation in the sentence ""This observation suggests that << MDMA >>-induced reductions in [[ SERT ]] density do not represent neuroadaptive responses to decreased levels of brain serotonin, but may occur in response to some other stimulus or to the neurotoxic effects of MDMA.""? downregulator Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""<< 2-Deoxyglucose >> increased phosphorylation of [[ tuberous sclerosis complex 2 ]] (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2.""? activator Question: What is the relation in the sentence ""RGM-1 cells were treated with << CDCA >> or GW4064, an [[ FXR ]] agonist, in the presence or absence of guggulsterone, an FXR antagonist.""? agonist Question: What is the relation in the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""Synthesis and in Vitro Characterisation of Ifenprodil-Based << Fluorescein >> Conjugates as [[ GluN1 ]]/GluN2B N-Methyl-D-aspartate Receptor Antagonists.""? antagonist Question: What is the relation in the sentence ""AMCA (0.06 mM) and << EACA >> (0.6 mM) were effective in prolonging clot lysis if (1) whole blood clots were formed and then exposed to a lysine analogue and exogenous [[ t-PA ]] or if (2) whole blood clots were formed in the presence of exogenous t-PA and a lysine analogue.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 410,"Regarding the sentence ""<< DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005)."", what is the relation? upregulator Regarding the sentence ""In addition, cobalt protoporphyrin (<< CoPP >>), a specific [[ HO-1 ]] inducer, predominantly suppressed LPS-induced NO production."", what is the relation? activator Regarding the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor Regarding the sentence ""Improvements from baseline in mean << glycosylated haemoglobin >> (HbA(1c)) were significantly greater with [[ sitagliptin ]] monotherapy than with placebo in patients with type 2 diabetes."", what is the relation? indirect-upregulator Regarding the sentence ""We have examined the effect of dihydropyridine << Ca2+-channel >> blockers felodipine and [[ nicardipine ]] on CaMPDE."", what is the relation? inhibitor Regarding the sentence ""The anti-hyperthermic effect of Lu AF21934 (5 mg/kg) in the SIH test was inhibited by the << benzodiazepine receptor >> antagonist [[ flumazenil ]] (10 mg/kg) and was not serotonin-dependent, as it persisted in serotonin-deficient mice and upon blockade of either 5-HT(1A) receptors by WAY100635, or 5-HT(2A/2C) receptors by ritanserin."", what is the relation? antagonist Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""Moreover, in rat hepatoma H4-II-E cells, the esterified-<< BM >> failed to induce tyrosine aminotransferase, which is regulated by [[ GR ]]-mediated transactivation activity."", what is the relation? agonist Regarding the sentence ""<< Dexamethasone >> (DEX) inhibited the anti-CD3-induced production of IL-4, [[ IL-5 ]] and IFN-gamma in all 20 clones tested."", what is the relation? indirect-downregulator Regarding the sentence ""To determine whether << 3,4-methylenedioxymethamphetamine >> (MDMA)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured."", what is the relation? downregulator Regarding the sentence ""<< L-serine dehydratase >> (SDH), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield [[ pyruvate ]] or 2-oxobutyrate."", what is the relation? product-of Regarding the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator Regarding the sentence ""The alpha class << human GSTA4-4 >> enzyme (hGSTA4-4) has a particularly high catalytic efficiency toward [[ 4-HNE ]] conjugation."", what is the relation? substrate Regarding the sentence ""Here we found that << arsenic trioxide >>, a frontline agent for acute promyelocytic leukemia, inhibits [[ ΔNp63 ]] but not TAp63 expression in time- and dose-dependent manners."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 411,"Consider the text ""The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (<< NF-κB >>) genes expression in [[ cisplatin ]] injected rats."". Can you identify the relation? indirect-downregulator Consider the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""We have examined the effect of dihydropyridine << Ca2+-channel >> blockers felodipine and [[ nicardipine ]] on CaMPDE."". Can you identify the relation? inhibitor Consider the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of << L-leucine >> for [[ leucine aminopeptidase ]], 4-methoxy-2-naphthylamide of L-glutamic acid for aminopeptidase A and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B."". Can you identify the relation? substrate Consider the text ""Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately [[ levobetaxolol ]]>levobunolol approximately carteolol>/=timolol>atenolol."". Can you identify the relation? antagonist Consider the text ""<< PIP5K1B >> encodes phosphatidylinositol 4-phosphate 5-kinase β type I (pip5k1β), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4-phosphate [PI(4)P] to generate phosphatidylinositol-4,5-bisphosphate [[[ PI(4,5)P2 ]]]."". Can you identify the relation? product-of Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]]."". Can you identify the relation? upregulator Consider the text ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in << MSG >>-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased [[ pIR ]] by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."". Can you identify the relation? downregulator Consider the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full << muscarinic receptor >> agonist [[ methacholine ]], the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine."". Can you identify the relation? agonist Consider the text ""The results of this study suggest that << noradrenaline >> predominantly, but not exclusively, mediates contraction of rat aorta through the activation of an [[ alphalD-adrenoceptor ]]."". Can you identify the relation? activator Consider the text ""<< Ozone >> plus PM(2.5) exposure, however, induced CRP, [[ IL-6 ]], CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way."". Can you identify the relation? indirect-upregulator Consider the text ""Additionally, these effects of << ATO >> on γ-[[ H2AX ]], Chk1, Chk2, p53, and p21(waf1/cip1) were reduced by an ATM inhibitor."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 412,"In reference to ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, << SNAP 1069 >> and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]."", what is the relation? antagonist In reference to ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system."", what is the relation? product-of In reference to ""In fact, we demonstrated a significant stimulation of << Nox4 >> activity by 4 quinone derivatives (AA-861, tBuBHQ, [[ tBuBQ ]], and duroquinone) observed in 3 different cellular models, HEK293E, T-REx™, and chondrocyte cell lines."", what is the relation? activator In reference to ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator In reference to ""Objective: This study explores the ability of << acyl glucuronides >> to act as substrates or inhibitors of human carboxylesterases 1 ([[ hCES1 ]]) and 2 (hCES2)."", what is the relation? substrate In reference to ""Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal NGF, [[ BDNF ]] and ChAT that was eliminated by olanzapine treatment."", what is the relation? indirect-downregulator In reference to ""The anti-amnesic effect of minaprine on the cycloheximide-induced memory impairment was also antagonized by a serotonin (5-HT) releaser, p-chloroamphetamine, and by a 5-HT precursor, 5-hydroxytryptophan, whereas a << 5-HT1A >>-selective agonist, [[ 8-hydroxy-2-(di-n-propylamino)tetralin ]], was inactive."", what is the relation? agonist In reference to ""<< NaAsO(2) >> increased the mRNA levels of the [[ light and medium subunits of neurofilament ]] and decreased the mRNA levels of tau and tubulin in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin."", what is the relation? indirect-upregulator In reference to ""Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity."", what is the relation? downregulator In reference to ""<< Am80 >> inhibited [[ VEGF ]]-induced phosphorylation of VEGF receptor."", what is the relation? inhibitor In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line."", what is the relation? upregulator In reference to ""Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (<< BuChE >>) considered to play a minor role in regulating brain [[ acetylcholine ]] (ACh) levels."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 413,"Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked << ABCA1 >>-mediated [[ cholesterol ]] efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM). Please explain the relation. substrate CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme. Please explain the relation. upregulator BACKGROUND: << Histamine >> synthesized by [[ histidine decarboxylase ]] (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity. Please explain the relation. product-of Both 5 alpha-NET and << 3 beta,5 alpha-NET >> blocked the [[ PR ]] down-regulation induced by P4 as assessed by Western and Northern blot methods. Please explain the relation. indirect-upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Please explain the relation. substrate_product-of This study assessed changes in myocardial ALDH2 expression in the diabetic rat, in particular the diabetic rat pretreated with << ALDH2 >> activator [[ ethanol ]] (EtOH). Please explain the relation. activator Association of PGE2 or << acetazolamide >> to NSAIDs reduced NSAID-induced activation of CA I and [[ CA II ]]. Please explain the relation. downregulator Docetaxel is a semisynthetic << taxane >> that inhibit tumor growth by induction of microtubule stabilization and promotion of [[ bcl-2 ]] inactivation, which induce apoptosis. Please explain the relation. indirect-downregulator Assays examining the ability of TFP to block S100A4-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of << S100A4 >> function occurs only at [[ TFP ]] concentrations that promote S100A4 oligomerization. Please explain the relation. inhibitor EP(1) and EP(3) receptor antagonists ONO-8713 and ONO-AE3-240, but not the << EP(4) >> antagonists ONO-AE3-208 and [[ AH 23848 ]], inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth. Please explain the relation. antagonist << Ramelteon >> (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin MT(1)/[[ MT(2) ]] receptor agonist. Please explain the relation. agonist The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Of the rat CYP isoforms studied, << CYP2D >> isoforms were the most efficient in catalyzing the O-demethylation of [[ 5-methoxytryptamine ]] to serotonin, but they were less effective than the human isoform CYP2D6. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 414,"Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Dexamethasone >> (DEX), betamethasone (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]. Query: What is the relation? agonist << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator << Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS). Query: What is the relation? product-of In concert with these results, we highlighted that the secretion of pro-inflammatory << cytokine >> and NF-κB activation induced by [[ TCDD ]] can be mediated by elevation of [Ca(2+)]i in HAPI microglial cells. Query: What is the relation? activator A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the << VEGFR >> tyrosine kinase inhibitors sunitinib and/or [[ sorafenib ]]. Query: What is the relation? inhibitor L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of [[ L-serine ]] and L-threonine to yield pyruvate or 2-oxobutyrate. Query: What is the relation? substrate Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor << chloramine T >> (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin. Query: What is the relation? downregulator Both 5 alpha-NET and << 3 beta,5 alpha-NET >> blocked the [[ PR ]] down-regulation induced by P4 as assessed by Western and Northern blot methods. Query: What is the relation? indirect-upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Query: What is the relation? substrate_product-of << Betaxolol >>, a [[ beta(1)-adrenoceptor ]] antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other beta-adrenoceptor antagonists. Query: What is the relation? antagonist << Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity. Query: What is the relation? upregulator << PTE >> also down-regulated the expression of [[ STAT3 ]] target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. Query: What is the relation? indirect-downregulator Metformin and << phenformin >> activate [[ AMP-activated protein kinase ]] in the heart by increasing cytosolic AMP concentration. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 415,"Given the text ""Interestingly, part of << MCT2 >> immunoreactivity is located at postsynaptic sites, suggesting a particular role of [[ monocarboxylates ]] and their transporters in synaptic transmission."", describe the relation. substrate Given the text ""<< Theophylline >> exposure resulted in a sustained increase in mRNA expression for [[ CysS ]] and PDE3A, but PDE4D gene expression was unchanged."", describe the relation. indirect-upregulator Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""<< Tomudex >> treatment resulted in the decrease in p27(kip1) expression, with an increase in cyclin E and cdk2 protein expression and [[ kinase ]] activities 24 h after a 2-h exposure."", describe the relation. activator Given the text ""These results suggest that the altered gamma-glutamyl kinase results in stabilization of the complex or has an indirect effect on << gamma-glutamyl phosphate reductase >> activity, which leads to an increase in [[ L-proline ]] production in Saccharomyces cerevisiae."", describe the relation. product-of Given the text ""<< 5-Fluorouracil >> (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine (F3(d)Thd) are antimetabolites which are metabolized to their corresponding active forms which inhibit DNA synthesis via inhibition of thymidylate synthase ([[ TS ]])."", describe the relation. inhibitor Given the text ""These results indicate that << U50,488H >>-induced down-regulation of the [[ hkor ]] involves GRK-, arrestin-2-, dynamin-, rab5-, and rab7-dependent mechanisms and receptors seem to be trafficked to lysosomes and proteasomes for degradation."", describe the relation. downregulator Given the text ""Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats."", describe the relation. upregulator Given the text ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", describe the relation. agonist-activator Given the text ""Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and transforming growth factor-β1 (<< TGF-β1 >>), were reduced in rats treated with [[ sinapic acid ]]."", describe the relation. indirect-downregulator Given the text ""Compared pharmacological characteristics in humans of racemic cetirizine and << levocetirizine >>, two [[ histamine H1-receptor ]] antagonists."", describe the relation. antagonist Given the text ""<< Noradrenaline >> and phenylephrine ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively."", describe the relation. agonist Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""However, both compounds have similar molecular mechanisms of neuroprotection in neuronal cell cultures and animal neurodegenerative models, indicating that the neuroprotective effect of << rasagiline >> does not depend on inhibition of [[ MAO-B ]], but rather is associated with the N-propargyl moiety, which promotes mitochondrial viability and stabilizes permeability transition by regulating Bcl-2 family proteins."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 416,"In reference to ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of In reference to ""<< Reboxetine >>, a selective norepinephrine reuptake inhibitor, exhibits high affinity and selectivity for the [[ human norepinephrine transporter ]]."", what is the relation? inhibitor In reference to ""Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the << phillyrin >>-enhanced activation of [[ AMPK ]] in HepG2 hepatocytes."", what is the relation? activator In reference to ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor In reference to ""<< Insulin >> secretion stimulated by both 200 μM tolbutamide and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1 μM) or the L-type Ca(2+) channel blocker nicardipine (2 μM) and was potentiated by [[ 8-pCPT-2'-O-Me-cAMP-AM ]] at concentrations ≥2 μM in INS-1 cells."", what is the relation? indirect-upregulator In reference to ""Although generally highly specific for << angiotensin II type 1 receptors >>, some ARBs, particularly [[ telmisartan ]], are partial agonists at peroxisome proliferator-activated receptor-γ."", what is the relation? antagonist In reference to ""Megalin, a family of endocytic receptors related to the << low-density lipoprotein (LDL) receptor >>, is a major pathway for proximal tubular [[ aminoglycoside ]] accumulation."", what is the relation? substrate In reference to ""BACKGROUND & AIMS: Of the 2 genes (MAT1A, MAT2A) encoding methionine adenosyltransferase, the enzyme that synthesizes << S-adenosylmethionine >>, [[ MAT1A ]], is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues."", what is the relation? product-of In reference to ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator In reference to ""Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist salbutamol 8 mg ([[ SAL ]]), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors."", what is the relation? agonist In reference to ""<< Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity."", what is the relation? upregulator In reference to ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."", what is the relation? downregulator In reference to ""Cotreatment with U0126 and << YC-1 >> synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, JNK, and [[ beta-catenin ]]."", what is the relation? indirect-downregulator In reference to ""Levels of mRNA encoding << insulin 1 >>, ICA512, and PC1/3 were increased in the pancreatic islets of [[ GalN ]]-treated rats."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 417,"Regarding ""<< Betaxolol >>, a [[ beta(1)-adrenoceptor ]] antagonist used for the treatment of glaucoma, is known to be neuroprotective in paradigms of ischaemia/excitotoxicity."", can you determine the relation? antagonist Regarding ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", can you determine the relation? agonist-activator Regarding ""In activated microglia, << 15d-PGJ2 >> suppressed iNOS promoter activity, [[ iNOS ]] mRNA, and protein levels."", can you determine the relation? indirect-downregulator Regarding ""These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves."", can you determine the relation? agonist Regarding ""Using a unique biosensor-based assay, << trifluoperazine >> (TFP) was identified as an inhibitor that disrupts the S100A4/[[ myosin-IIA ]] interaction."", can you determine the relation? inhibitor Regarding ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", can you determine the relation? agonist-inhibitor Regarding ""<< N(5)-Substituted H(4)biopterin >> derivatives were not oxidized to products serving as substrates for [[ dihydropteridine reductase ]] and,depending on the substituent, were competitive inhibitors of phenylalanine hydroxylase: N(5)-methyl- and N(5)-hydroxymethyl H(4)biopterin inhibited phenylalanine hydroxylase, whereas N(5)-formyl- and N(5)-acetyl H(4)biopterin had no effect."", can you determine the relation? substrate Regarding ""SIRT1 co-precipitated with PPARα and << nicotinamide >> increased the acetylation of the PPARα coactivator [[ PGC-1α ]], which was suppressed by resveratrol."", can you determine the relation? activator Regarding ""High << glucose >> (HG) induces apoptosis of podocytes, inhibits AMPK activation, inactivates [[ tuberin ]] and activates mTOR."", can you determine the relation? downregulator Regarding ""Both 5 alpha-NET and << 3 beta,5 alpha-NET >> blocked the [[ PR ]] down-regulation induced by P4 as assessed by Western and Northern blot methods."", can you determine the relation? indirect-upregulator Regarding ""Platelet-induced << COX-2 >>-dependent [[ PGE2 ]] synthesis in HT29 cells was involved in downregulation of p21(WAF1/CIP1) and upregulation of cyclinB1, since these effects were prevented by rofecoxib(a selective COX-2 inhibitor) and rescued by exogenous PGE2."", can you determine the relation? product-of Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line."", can you determine the relation? upregulator Regarding ""<< Phenformin >> but not metformin inhibits a number of variants of [[ K(ATP) ]] including the cloned equivalents of currents present in vascular and non-vascular smooth muscle (Kir6.1/SUR2B and Kir6.2/SUR2B) and pancreatic beta-cells (Kir6.2/SUR1)."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 418,"Given the text ""RESULTS: Fractionated bulb extracts and the two isolated << steroidal glycoalkaloids >> (1) and (2) induced NO production and [[ TGF-β receptor I ]] mRNA expression in fibroblast cell culture."", describe the relation. indirect-upregulator Given the text ""<< Vegfrecine >>, an Inhibitor of [[ VEGF Receptor Tyrosine Kinases ]] Isolated from the Culture Broth of Streptomyces sp."", describe the relation. inhibitor Given the text ""However the regulatory mechanism of << histamine >> synthesis by [[ HDC ]] remains to be elucidated."", describe the relation. product-of Given the text ""<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted ([[ DeltaKPQ ]]) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings."", describe the relation. downregulator Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""<< Amitriptyline >> is a [[ TrkA ]] and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity."", describe the relation. agonist Given the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of [[ p21 ]](WAF1/CIP1) and p53."", describe the relation. upregulator Given the text ""Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the dopamine D1 receptor antagonist SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine) and the << dopamine D2 receptor >> antagonist [[ raclopride ]] (both at 0.003-0.03 mg/kg)."", describe the relation. antagonist Given the text ""In the << IB-MECA >> group, [[ α-amylase ]] activity was decreased with statistically high significance compared to group I."", describe the relation. indirect-downregulator Given the text ""Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4-methoxy-2-naphthylamide of L-alanine for aminopeptidase N, 4-methoxy-2-naphthylamide of L-leucine for leucine aminopeptidase, 4-methoxy-2-naphthylamide of << L-glutamic acid >> for [[ aminopeptidase A ]] and 4-methoxy-2-naphthylamide of L-arginine for aminopeptidase B."", describe the relation. substrate Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""In alpha2B-receptor-expressing HEK293 cells, << etomidate >> rapidly increased phosphorylation of the extracellular signal-related kinases [[ ERK1/2 ]]."", describe the relation. activator Given the text ""We demonstrate that two flavin mono-oxygenase family members, << FMO1 >> and FMO3, oxidize trimethylamine (TMA), derived from gut flora metabolism of choline, to [[ TMAO ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 419,"Regarding ""<< Nitrogen >>-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of [[ Ras ]] signaling pathways and Bim-mediated activation of the intrinsic apoptotic pathway."", can you determine the relation? inhibitor Regarding ""These results suggest that << HSD11B1 >>-derived [[ cortisol ]] mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep."", can you determine the relation? product-of Regarding ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", can you determine the relation? agonist-activator Regarding ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively."", can you determine the relation? upregulator Regarding ""Increased immunohistochemical labeling of HIF-1alpha, VEGF, and << BNP >> in the ventricular myocardium was observed in the shunt group and [[ carvedilol ]] again normalized the labeling."", can you determine the relation? indirect-downregulator Regarding ""Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits << p22(phox) >> and NOX4, which were prevented by [[ resveratrol ]]."", can you determine the relation? downregulator Regarding ""In further studies, the diuretic effects of the << CB1 >> agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with [[ rimonabant ]], but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]."", can you determine the relation? antagonist Regarding ""The studies with dThyd rescue from << cyclin E >>-cdk2 protein overexpression and growth inhibition by [[ Tomudex ]] indicate that increased cyclin E-cdk2 protein expression is associated with effective inhibition of thymidylate synthase and resultant dNTP pool imbalance."", can you determine the relation? indirect-upregulator Regarding ""Overall, our findings suggest that << ursolic acid >> induced apoptosis in HepG2 cells via AMPK activation and [[ GSK3β ]] phosphorylation as a potent chemopreventive agent."", can you determine the relation? activator Regarding ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""The protein exhibited modest H(2)O(2)-dependent << peroxidase >> activities with guaiacol, potassium iodide, and [[ 2,2(')-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid ]] (ABTS)."", can you determine the relation? substrate Regarding ""The use of << A3 receptor >> agonist [[ IB-MECA ]] attenuates EAP."", can you determine the relation? agonist Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""In rat striatum and nucleus accumbens, mianserin stimulated [35S]GTPgammaS binding in a nor-BNI-sensitive manner with maximal effects lower than those of the full << kappa-opioid >> agonists (-)-U50,488 and [[ dynorphin A ]]."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 420,"The results showed that administration of << AlCl3 >> resulted in a significant elevation in the levels of [[ AchE ]] activity, CRP, NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level. Question: what is the relation? Answer: upregulator Galanin attenuates << cyclic AMP regulatory element-binding protein >> (CREB) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures. Question: what is the relation? Answer: activator << Adenine phosphoribosyltransferase >> plays a role in purine salvage by catalyzing the direct conversion of adenine to [[ adenosine monophosphate ]]. Question: what is the relation? Answer: product-of Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective << alpha(1D)-adrenoceptor >> antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively). Question: what is the relation? Answer: agonist In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: agonist-activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of [[ PI3K ]]/Akt/GSK-3β signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc. Question: what is the relation? Answer: indirect-downregulator << Carboxylesterases >> hydrolyze esters, [[ amides ]], and thioesters to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively. Question: what is the relation? Answer: substrate << PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins ([[ Bax ]], Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. Question: what is the relation? Answer: indirect-upregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]]). Question: what is the relation? Answer: substrate_product-of Discovery and optimization of << anthranilic acid sulfonamides >> as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of [[ albumin ]] binding. Question: what is the relation? Answer: downregulator The non-selective adenosine receptor antagonist (caffeine), and the selective << adenosine A1 receptor >> antagonist ([[ DPCPX ]]), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice. Question: what is the relation? Answer: antagonist First, in the presence of 1 mm ATP or the nonhydrolyzable analog adenosine 5'-(beta,gamma-imino)triphosphate, TOP2-mediated DNA cleavage induced by ATP-sensitive << TOP2 >> poisons (e.g. [[ doxorubicin ]], etoposide, mitoxantrone, and 4'-(9-acridinylamino)methanesulfon-m-anisidide) was 30-100-fold stimulated, whereas DNA cleavage induced by ATP-insensitive TOP2 poisons (e.g. amonafide, batracylin, and menadione) was only slightly (less than 3-fold) affected. Question: what is the relation? Answer: inhibitor Results indicate that << imiquimod >> and resiquimod induce [[ IFN-alpha ]] and IFN-omega from purified pDC, and pDC are the principle IFN-producing cells in the blood. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 421,"Regarding ""PURPOSE: The << fluoropyrimidine carbamate >> (capecitabine) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues."", can you determine the relation? substrate Regarding ""The two basic mainstays of gastrointestinal stromal tumours (GIST) treatment are surgery and << imatinib >>, a selective [[ tyrosine kinase ]] inhibitor that allows achieving a stable or responding disease in about 80% of patients with unresectable/metastatic GIST."", can you determine the relation? inhibitor Regarding ""In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor [[ NF-κB ]], HSF1, AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins."", can you determine the relation? activator Regarding ""In addition, << ethanol >> induced degradation of [[ DNA methyltransferases ]] (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, MBD-2 and MBD-3), in MEF cells by the proteasomal pathway."", can you determine the relation? downregulator Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""In four (10 %) patients the peak << ACTH >>-stimulated [[ cortisol ]] values were lower than 18 μg/dL."", can you determine the relation? product-of Regarding ""This initial action was accompanied by up-regulation of cyclooxygenase-2 (<< COX-2 >>), an important inflammation marker within 1h after [[ TCDD ]] treatment."", can you determine the relation? indirect-upregulator Regarding ""Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (<< TCDD >>) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced [[ Cx43 ]] protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner."", can you determine the relation? indirect-downregulator Regarding ""The results suggested that both the EtOAc extract and berberine were able to activate PPARα/β/γ, and Rhizoma Coptis contains potential natural agonists of << PPARs >> besides [[ berberine ]]."", can you determine the relation? agonist Regarding ""<< beta(1)-Adrenoceptor >> antagonism (10 mg kg(-1) [[ bisoprolol ]]) prevented 92% (P < 0.05) of apoptosis induced by all three agonists, but clenbuterol-induced apoptosis could also be prevented by 96% (P < 0.05) by beta(2)-AR antagonism (10 mg kg(-1) ICI 118 551)."", can you determine the relation? antagonist Regarding ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", can you determine the relation? agonist-activator Regarding ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport."", can you determine the relation? upregulator Regarding ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""Moreover, compared with the model group, << sophocarpine >> could significantly increase P-AMPKα (>5.82-fold), AMPKα (>1.29-fold) and ACC (>3.27-fold) protein expressions, and reduce [[ P-ACC ]] (<0.30-fold) and HNF-4α (<0.20-fold) protein expression."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 422,"In conclusion, << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist timolol. Query: What is the relation? activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Query: What is the relation? agonist-inhibitor Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced << NO >> inhibition, which was followed by suppression of [[ HO-1 ]] activity. Query: What is the relation? downregulator The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator Moreover, protein and mRNA levels of DSS-induced proinflammatory << cytokines >> in colon, including TNF-α, IL-1β, IL-18, IL-17A and IFN-γ, were markedly suppressed by [[ Fc11a-2 ]]. Query: What is the relation? indirect-downregulator 2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery. Query: What is the relation? agonist << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of Blockade of PDE1 (8-methoxymethyl-3-isobutyl-1-methylxanthine, 100 microM), PDE2 [erythro-9-(2-hydroxy-3-nonyl)adenine, 30 microM], PDE3 (milrinone, 10 microM; cGMP, 10 microM), << PDE4 >> (Ro 20-1724 [[[ 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one ]]], 100 microM), PDE5 and PDE6 (zaprinast, 30 microM), and PDE7 [BRL-50481 (5-nitro-2,N,N-trimethylbenzenesulfonamide), 10 microM] did not alter renal ecto-phosphodiesterase activity. Query: What is the relation? inhibitor Alprenolol and << BAAM >> also caused surmountable antagonism of isoprenaline responses, and this [[ beta 1-adrenoceptor ]] antagonism was slowly reversible. Query: What is the relation? antagonist Addition of << putrescine >> restored the induction of apoptosis as indicated by an increase in the number of detached cells and [[ caspase 3 ]] activity. Query: What is the relation? upregulator We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as ascorbate peroxidase ([[ APX ]]). Query: What is the relation? product-of << Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites ([[ o-quinones ]]) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis. Query: What is the relation? substrate On study day 1, << candoxatril >> acutely increased plasma [[ ANP ]] levels, suppressed aldosterone and decreased right atrial and pulmonary capillary wedge pressures. Query: What is the relation? indirect-upregulator The elevation in brain << alanine >> levels could be explained, at least in part, by a time- and dose-dependent inhibitory effect of PLZ on [[ alanine transaminase ]] (ALA-T), although as with GABA the increases are higher than expected from the degree of enzyme inhibition produced. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 423,"Given the text ""<< PTE >> also down-regulated the expression of [[ STAT3 ]] target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27."", describe the relation. indirect-downregulator Given the text ""<< LY541850 >> was claimed from human mGlu receptors expressed in non-neuronal cells to be a selective orthosteric [[ mGlu2 ]] agonist and mGlu3 antagonist."", describe the relation. agonist Given the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""<< HSYA >> treatment also decreased [[ NF-κB ]] p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK)."", describe the relation. downregulator Given the text ""Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, thymidine kinase-1 and [[ thymidylate synthase ]], in various types of cancer."", describe the relation. product-of Given the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", describe the relation. agonist-activator Given the text ""Furthermore, << BRN-250 >> inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream [[ AKT ]] pathway."", describe the relation. inhibitor Given the text ""<< Indomethacin >> treatment led to an increase in lipid peroxidation, glutathione peroxidase and [[ glucose-6-phosphate dehydrogenase ]] activities and to a decrease in catalase activity and glutathione levels in gastric mucosa."", describe the relation. activator Given the text ""<< Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line."", describe the relation. upregulator Given the text ""<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic [[ Cytochrome c ]], and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27."", describe the relation. indirect-upregulator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""These five CGPs also inhibited << [(3)H]E217βG >> uptake by [[ MRP4 ]]."", describe the relation. substrate Given the text ""Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect of an << NR2B >> subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model."", describe the relation. antagonist Given the text ""ICI118,551 HCl (1.25-5 mg/kg, IP), a selective beta 2-adrenoceptor antagonist, also blocked the desipramine-induced enhancement of aggressive behavior in a dose-dependent manner, whereas << metoprolol tartrate >> (5-20 mg/kg, IP), a selective [[ beta 1-adrenoceptor ]] antagonist, did not affect it."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 424,"Question: What is the relation in the sentence ""After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial << muscarinic receptor >> agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and [[ histamine ]].""? agonist Question: What is the relation in the sentence ""<< U50, 488H >> caused a significant down-regulation of the [[ hkor ]], although etorphine did not.""? downregulator Question: What is the relation in the sentence ""We report here that << lovastatin >>, a drug clinically used for lowering cholesterol levels, inhibits the interaction of human LFA-1 with its counter-receptor [[ intercellular adhesion molecule-1 ]].""? inhibitor Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""The results show that CYP2E1 inhibits << CYP2B4 >>-mediated metabolism of benzphetamine ([[ BNZ ]]) with a K(i) of 0.04 µM.""? substrate Question: What is the relation in the sentence ""Expression of << L-type pyruvate kinase >> (L-PK) is upregulated in the liver by dietary [[ carbohydrate ]].""? indirect-upregulator Question: What is the relation in the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2.""? agonist-inhibitor Question: What is the relation in the sentence ""Time-dependent changes in hepatic and intestinal induction of << cytochrome P450 3A >> after administration of [[ dexamethasone ]] to rats.""? activator Question: What is the relation in the sentence ""<< Mouse brain serine racemase >> catalyzes specific elimination of L-serine to [[ pyruvate ]].""? product-of Question: What is the relation in the sentence ""Moreover, we found that << juglone >> significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and [[ PSA ]] genes with and/or without dihydrotestosterone (DHT).""? indirect-downregulator Question: What is the relation in the sentence ""CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme.""? upregulator Question: What is the relation in the sentence ""Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.""? antagonist Question: What is the relation in the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol.""? agonist-activator Question: What is the relation in the sentence ""The << sodium channel >>-blocking action of [[ cocaine ]] per se does not appear to be involved in the rapid pressor response to cocaine.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 425,"Moreover, << curcumin >> alleviated [[ Sim2 ]] expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia. Query: What is the relation? indirect-upregulator << Terbutaline >> (Bricanyl) and its prodrug Bambuterol (Bambec) are highly potent [[ beta(2)-adrenoceptor ]] agonists often used in asthma patients. Query: What is the relation? agonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme. Query: What is the relation? upregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Query: What is the relation? agonist-activator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Query: What is the relation? substrate_product-of These results indicate that the positive inotropic effect, mediated via << (+/-)-tamsulosin >>- and oxymetazoline-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates. Query: What is the relation? antagonist METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of << [(3)H] dopamine >> (DA) uptake and [(3)H]WIN 35428 binding in human dopamine transporter ([[ DAT ]]) wild-type and mutants with altered conformational equilibria. Query: What is the relation? substrate The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), << tumor necrosis factor alpha >> (TNF-α), nuclear factor kappa B (NF-κB) genes expression in [[ cisplatin ]] injected rats. Query: What is the relation? indirect-downregulator Hydrogen sulphide (<< H(2)S >>) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS). Query: What is the relation? product-of << Amprenavir >>-mediated [[ PXR ]] activation stimulated the expression of several key intestinal genes involved in lipid homeostasis. Query: What is the relation? activator Everolimus (RAD001, << Afinitor((R)) Novartis >>) is the first oral inhibitor of [[ mTOR ]] (mammalian target of rapamycin) to reach the oncology clinic. Query: What is the relation? inhibitor The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice ([[ MSG ]], 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). Query: What is the relation? downregulator Nisoldipine (a << DHP >> antagonist) blocks the [[ smooth muscle channel ]] more potently than the cardiac one, a phenomenon observed not only in native channels but also in expressed channels. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 426,"Regarding the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", what is the relation? agonist-activator Regarding the sentence ""By reporter gene analysis following transient transfections with various plasmids expressing a dominant negative mutant form of Cdc42, Rac1 or RhoA, << C2-ceramide >>-induced [[ SRE ]] activation was shown to be selectively repressed by pEXV-RacN17 encoding a dominant negative mutant of Rac1, suggesting that Rac activity is essential for the signalling cascade of ceramide to the nucleus."", what is the relation? activator Regarding the sentence ""<< (R)-Ketoprofen >> (1) was previously reported to be a potent and specific noncompetitive inhibitor of [[ CXCL8 ]]-induced human PMNs chemotaxis."", what is the relation? inhibitor Regarding the sentence ""Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and [[ Dkk2 ]]) of the pathway."", what is the relation? downregulator Regarding the sentence ""(+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and << RS 17053 >> appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]."", what is the relation? antagonist Regarding the sentence ""Fumarate reductase (<< FRD >>) is the key enzyme in [[ fumarate ]] respiration induced by anaerobic growth of bacteria."", what is the relation? substrate Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure."", what is the relation? agonist Regarding the sentence ""The inhibition of << UG >> synthesis and PR down-regulation by 5 alpha-NET and 3 beta,5 alpha-NET indicates that these [[ NET ]] metabolites possess antiprogestational properties."", what is the relation? indirect-downregulator Regarding the sentence ""Activation of an apoptotic signal transduction pathway involved in the upregulation of calpain and << apoptosis-inducing factor >> in [[ aldosterone ]]-induced primary cultured cardiomyocytes."", what is the relation? indirect-upregulator Regarding the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor Regarding the sentence ""<< Butein >> also increased heme oxygenase-1 (HO-1) protein expression and [[ HO ]] activity."", what is the relation? upregulator Regarding the sentence ""Reduced synthesis of nitric oxide (<< NO >>) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II."", what is the relation? product-of Regarding the sentence ""In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase ([[ iNOS ]]), and tumor necrosis factor-α (TNF- α)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 427,"Regarding the sentence ""<< Betaxolol >>, a beta(1)-adrenoceptor antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other [[ beta-adrenoceptor ]] antagonists."", what is the relation? antagonist Regarding the sentence ""Dexamethasone (DEX), betamethasone (<< BM >>), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]."", what is the relation? agonist Regarding the sentence ""The mRNA levels of << microphthalmia-associated transcription factor >> (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment."", what is the relation? indirect-downregulator Regarding the sentence ""In concert with these results, we highlighted that the secretion of pro-inflammatory << cytokine >> and NF-κB activation induced by [[ TCDD ]] can be mediated by elevation of [Ca(2+)]i in HAPI microglial cells."", what is the relation? activator Regarding the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", what is the relation? agonist-activator Regarding the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]]."", what is the relation? upregulator Regarding the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Uptake of the radiolabeled model substrates << estradiol 17β-glucuronide >>, estrone 3-sulfate, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or [[ OATP1B3 ]]."", what is the relation? substrate Regarding the sentence ""Gastrointestinal adenocarcinomas and squamous cell uterine carcinomas were often accompanied by high << TS >> expression, indicating activation of [[ pyrimidine ]] synthesis through both the salvage and de novo pathways."", what is the relation? product-of Regarding the sentence ""Results showed that neonatal << quinpirole >> treatment induced [[ D2 ]] priming that was eliminated by olanzapine treatment."", what is the relation? indirect-upregulator Regarding the sentence ""However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of [[ metallothionein-II ]] production, and an increase in p53 activation and the pro-apoptotic protein Bax."", what is the relation? downregulator Regarding the sentence ""Again, inhibition of the actin-activated myosin Mg2+-ATPase and << myosin >> filament assembly by [[ felodipine ]] and the p-chloro analogue could be reversed by raising the calmodulin concentration."", what is the relation? inhibitor Regarding the sentence ""A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia, and the in vivo selectivity of a selective << cyclooxygenase (COX)-2 >> inhibitor ([[ celecoxib ]]) in comparison to a dual COX-1/COX-2 inhibitor (ketorolac)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 428,"In reference to ""METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist (SB-207266) on the [[ cisapride ]] mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects."", what is the relation? agonist In reference to ""METHODS: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of << [(3)H] dopamine >> (DA) uptake and [(3)H]WIN 35428 binding in [[ human dopamine transporter ]] (DAT) wild-type and mutants with altered conformational equilibria."", what is the relation? substrate In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and << purine nucleoside phosphorylase >> was increased in the [[ 2-chlorodeoxyadenosine ]]-selected line."", what is the relation? upregulator In reference to ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""(3)H-CGP 12177A saturation binding, in the presence of << propranolol >>, increased approximately 5-fold following overexpression of [[ beta(1)-adrenoceptors ]]."", what is the relation? indirect-upregulator In reference to ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of [[ Lef1 ]], Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD."", what is the relation? indirect-downregulator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Central << 5-HT3 >> receptor stimulation by [[ m-CPBG ]] increases blood glucose in rats."", what is the relation? activator In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of [[ cyclin D1 ]], cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator In reference to ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system."", what is the relation? product-of In reference to ""Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), << kushenol H >> ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on [[ diacylglycerol acyltransferase ]] (DGAT)."", what is the relation? inhibitor In reference to ""Selective antagonism of GluR5 << kainate-receptor >>-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons."", what is the relation? antagonist In reference to ""The << Bcl2 >>/Bax ratio increased and Mfn2 expression decreased in MIN6 cells after [[ glucose ]] stimulation."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 429,"Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< Rapamycin >> inhibits [[ proteinase ]] and selected peptidase activities of the catalytic core proteasome at low micromolar concentrations."", can you determine the relation? inhibitor Regarding ""At normal pH (7.4) and temperature (37 degrees C), the uptake of 1 microM << cefadroxil >> was reduced by 83% in [[ PEPT2 ]](-/-) mice as compared with PEPT2(+/+) mice (p < 0.001)."", can you determine the relation? substrate Regarding ""2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", can you determine the relation? agonist Regarding ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", can you determine the relation? substrate_product-of Regarding ""RESULTS: Ketorolac was six times more active against COX-1 (IC(50) = 0.02 microM) than << COX-2 >> (IC(50) = 0.12 microM) while [[ bromfenac ]] was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM)."", can you determine the relation? downregulator Regarding ""In conclusion, the production of IL-4 and << IL-5 >> by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by [[ DEX ]] than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma."", can you determine the relation? indirect-downregulator Regarding ""RORalpha ectopic expression activated the << cAspAT >> gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by [[ rosiglitazone ]] treatment of adipocytes."", can you determine the relation? indirect-upregulator Regarding ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", can you determine the relation? agonist-activator Regarding ""Ferredoxin 1 (<< FDX1 >>; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including [[ steroid ]] hormone synthesis in mammalian tissues."", can you determine the relation? product-of Regarding ""The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound [[ BT-07-4M ]], TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure."", can you determine the relation? activator Regarding ""These results indicate that the positive inotropic effect, mediated via << (+/-)-tamsulosin >>- and oxymetazoline-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates."", can you determine the relation? antagonist Regarding ""Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]."", can you determine the relation? upregulator Regarding ""The enzyme (<< TcCA >>) has a very high catalytic activity for the [[ CO(2) ]] hydration reaction, being similar kinetically to the human (h) isoform hCA II, although it is devoid of the His64 proton shuttle."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 430,"In reference to ""<< Adrenaline >> inhibits [[ insulin ]] secretion via pertussis toxin-sensitive mechanisms."", what is the relation? indirect-downregulator In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Differences in magnitude of Na(+)-dependent << l-alanine >> uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", what is the relation? upregulator In reference to ""The i.c.v. administration of very low doses of okadaic acid (0.001-1 pg/mouse) and << cantharidin >> (0.001-1 ng/mouse), which inhibit [[ PP2A ]], produced a dose-dependent antagonism of the antinociception induced by morphine (s.c.)."", what is the relation? inhibitor In reference to ""<< Multidrug resistance-associated proteins >> are involved in the transport of the [[ glutathione ]] conjugates of the ultimate carcinogen of benzo[a]pyrene in human Caco-2 cells."", what is the relation? substrate In reference to ""It is not yet clear whether << tamoxifen >> can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a [[ BRCA2 ]] mutation."", what is the relation? downregulator In reference to ""The potentiation of the contractile effect induced by 5-HT is only somewhat modified by deendothelialization, but abolished by the << thromboxane A2 receptor >> antagonists GR32191 and [[ ridogrel ]]."", what is the relation? antagonist In reference to ""In the CCl4 hepatotoxicity model, pre-treatment with PSM or << silymarin >> resulted in significantly increased activities of [[ ethylmorphine-N-demethylase ]] and aniline 4-hydroxylase activity and cytochrome P450, compared to the CCl4 only group."", what is the relation? activator In reference to ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery."", what is the relation? agonist In reference to ""CYP1A1 and << CYP1A2 >> mRNAs were also increased by [[ pelargonidin ]] in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", what is the relation? indirect-upregulator In reference to ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of In reference to ""Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of [[ L-proline ]] synthesis from L-glutamate and which together may form a complex in vivo."", what is the relation? product-of In reference to ""<< Cabozantinib >> (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, [[ KIT ]], AXL, and FLT3."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 431,"In reference to ""siRNA knockdown of p38 MAPK abrogated the ability of << anisomycin >> to synergistically induce [[ CYP2B6 ]] mRNA."", what is the relation? indirect-upregulator In reference to ""<< P2Y(2) receptor >> agonist [[ INS37217 ]] enhances functional recovery after detachment caused by subretinal injection in normal and rds mice."", what is the relation? agonist In reference to ""Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, [[ nuclear factor-kappaB ]] and activating protein-1, which were increased in fructose-fed rats."", what is the relation? upregulator In reference to ""Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of propranolol>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>[[ atenolol ]]."", what is the relation? antagonist In reference to ""In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), [[ superoxide dismutase ]] (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system."", what is the relation? indirect-downregulator In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""<< SNP >> inhibits the accumulation of HIF-1alpha, the regulatory subunit of [[ HIF-1 ]], and the transcriptional activation of HIF-1alpha via a mechanism that is not dependent on either NO or soluble guanylate cyclase."", what is the relation? inhibitor In reference to ""Chronic consumption of << alcohol >> also stimulated abrupt increases in pro-inflammatory cytokines such as nuclear factor (NF)-κB, [[ tumor necrosis factor (TNF)-α ]] and interleukin (IL)-1β in liver otherwise co-administration of CNF effectively suppressed production of these cytokines dose-dependently."", what is the relation? activator In reference to ""Reduced synthesis of << nitric oxide >> (NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and [[ mitochondrial arginase II ]]."", what is the relation? product-of In reference to ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Uptake of the radiolabeled model substrates estradiol 17β-glucuronide, << estrone 3-sulfate >>, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or [[ OATP1B3 ]]."", what is the relation? substrate In reference to ""<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted ([[ DeltaKPQ ]]) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings."", what is the relation? downregulator In reference to ""We examined the effect of JTH-601 (3- inverted question markN-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy)ethyl]-N-methylaminom ethyl inverted question mark-<< 4-methoxy-2,5,6-trimethylphenol hemifumarate >>), a new [[ alpha(1L)-adrenoceptor ]] antagonist, on prostatic function in isolated canine prostate and in anesthetized dogs."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 432,"Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", can you determine the relation? substrate_product-of Regarding ""The inhibition of << UG >> synthesis and PR down-regulation by 5 alpha-NET and [[ 3 beta,5 alpha-NET ]] indicates that these NET metabolites possess antiprogestational properties."", can you determine the relation? indirect-downregulator Regarding ""These results suggest that the megabase DNA fragmentation is induced as a consequence of inhibition of thymidylate synthase by << Tomudex >> and kilobase DNA fragmentation may correlate with the reduction of p27(kip1) expression and the increase in [[ cyclin E ]] and cdk2 kinase activities."", can you determine the relation? activator Regarding ""Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (<< Pin1 >>), an enzyme that catalyzes the conversion of the peptide bond of pSer/[[ pThr ]]-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification."", can you determine the relation? substrate Regarding ""Licofelone almost abolished << 5-LOX >> activity by inhibiting [[ leukotriene B4 ]] generation in rabbit neutrophils and prevented platelet thromboxane B2 production from whole blood."", can you determine the relation? product-of Regarding ""CONCLUSIONS: These results indicate that << etomidate >> acts as an agonist at [[ alpha2-adrenoceptors ]], which appears in vivo primarily as an alpha2B-receptor-mediated increase in blood pressure."", can you determine the relation? agonist Regarding ""Effects of a << serotonin 5-HT(4) receptor >> antagonist [[ SB-207266 ]] on gastrointestinal motor and sensory function in humans."", can you determine the relation? antagonist Regarding ""Expression of L-type pyruvate kinase (<< L-PK >>) is upregulated in the liver by dietary [[ carbohydrate ]]."", can you determine the relation? indirect-upregulator Regarding ""Gelatin zymography showed that << DMBT >> inhibited secretion and activity of [[ MMP-9 ]]."", can you determine the relation? inhibitor Regarding ""Moreover, recent in vitro studies suggest that << memantine >> abrogates beta-amyloid ([[ Abeta ]]) toxicity and possibly inhibits Abeta production."", can you determine the relation? downregulator Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", can you determine the relation? agonist-activator Regarding ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase ([[ CAT ]]) activity compared with the control."", can you determine the relation? upregulator Regarding ""Additional mechanistic studies revealed that << jaceosidin >> treatment resulted in an increase in phosphorylation of Cdc25C and [[ ATM ]]-Chk1/2."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 433,"Consider the text ""We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and [[ chalcone synthase ]] (CHS), and an antioxidant enzyme such as ascorbate peroxidase (APX)."". Can you identify the relation? product-of Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""The 5-HT(1/2/5/7)-receptor antagonist methysergide and the << 5-HT(2A/2B/2C)-receptor >> antagonist [[ LY 53857 ]] enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it."". Can you identify the relation? antagonist Consider the text ""While there is considerable indirect evidence to implicate << histamine >> in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early [[ H1-receptor ]] antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity."". Can you identify the relation? agonist Consider the text ""<< DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005)."". Can you identify the relation? upregulator Consider the text ""In conclusion, the production of IL-4 and << IL-5 >> by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by [[ DEX ]] than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma."". Can you identify the relation? indirect-downregulator Consider the text ""CRH caused a rise in plasma ACTH after both loperamide (from 30 +/- 16.6 to a peak of 108 +/- 31 pmol/l) and placebo (from 98.5 +/- 47 to 211 +/- 61.7 pmol/l): the interaction between treatments and time was significant, and the first phase of << CRH >>-induced ACTH secretion was significantly lower after [[ loperamide ]]."". Can you identify the relation? downregulator Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""Pretreatment with lysosomal enzyme inhibitors [(2S, 3S)trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester or chloroquine] or proteasome inhibitors (<< proteasome >> inhibitor I, [[ MG-132 ]], or lactacystin) decreased the extent of U50,488H-induced down-regulation."". Can you identify the relation? inhibitor Consider the text ""Moreover, << LTD4 >>-induced increases in CysLT(1)R and [[ NF-κB ]] p65 in the brain were also attenuated by pranlukast."". Can you identify the relation? indirect-upregulator Consider the text ""3. << CYP3A >> induction in the liver increased depending on the dose of DEX-P, whereas that in intestine showed a mild increase, but the induction level was almost constant regardless of the dose of [[ DEX-P ]]."". Can you identify the relation? activator Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""Specifically, << all-trans-13,14-dihydroretinol >> is transiently oxidized to all-trans-13,14-dihydroretinoic acid before being oxidized further by [[ Cyp26 ]] enzymes."". Can you identify the relation? substrate Consider the text ""Troglitazone, bosentan and glibenclamide inhibit the bile salt export pump (<< Bsep >>) which transports [[ taurocholate ]] into bile."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 434,"Given the text ""<< Aldose reductase >> (AR) catalyzes the reduction of toxic lipid aldehydes to their [[ alcohol ]] products and mediates inflammatory signals triggered by lipopolysaccharide (LPS)."", describe the relation. product-of Given the text ""<< EP(1) >> and EP(3) receptor antagonists [[ ONO-8713 ]] and ONO-AE3-240, but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."", describe the relation. antagonist Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Furthermore, V(5+) significantly inhibited the << TCDD >>-induced [[ AhR ]]-dependent luciferase activity."", describe the relation. indirect-upregulator Given the text ""<< CCl(4) >> administration triggered inflammatory response in mice livers by activating [[ nuclear factor-kappaB ]] (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2)."", describe the relation. activator Given the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""In contrast, the << D-1997 >>-induced responses were potently and concentration-dependently antagonized by the mixed 5-HT1-like and [[ 5-HT2 receptor ]] antagonist methiothepin (0.01-1 microM)."", describe the relation. agonist Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin ([[ HbA1c ]]), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin."", describe the relation. indirect-downregulator Given the text ""Racemization of << serine >> is catalyzed by [[ serine racemase ]], a pyridoxal 5'-phosphate-dependent enzyme expressed mainly in brain and liver."", describe the relation. substrate Given the text ""Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of VEGF and [[ MMP-9 ]] through Akt pathway in MDA-MB-231 breast cancer cells."", describe the relation. downregulator Given the text ""The selective PDE 4 inhibitors, and to a certain extent the << PDE3 >> inhibitors amrinone and [[ milrinone ]], reduced the GM-CSF release in a concentration dependent manner."", describe the relation. inhibitor Given the text ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", describe the relation. upregulator Given the text ""Wild-type enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and << Pro122Ser >>) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for [[ cytarabine ]] (Ara-C), dFdC, and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 435,"Consider the text ""Pasireotide (<< Signifor >>(®)) is a new subcutaneous somatostatin analogue that acts via somatostatin receptors to inhibit the secretion of [[ corticotropin ]] from the pituitary adenoma in patients with Cushing's disease."". Can you identify the relation? indirect-downregulator Consider the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."". Can you identify the relation? agonist-inhibitor Consider the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."". Can you identify the relation? agonist-activator Consider the text ""BACKGROUND: << Histamine >> synthesized by histidine decarboxylase ([[ HDC ]]) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity."". Can you identify the relation? product-of Consider the text ""Notably, << 17-HDHA >> treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression and improved glucose tolerance parallel to [[ insulin ]] sensitivity in obese mice."". Can you identify the relation? indirect-upregulator Consider the text ""Although the treatment with << MSG >> increased IRS-1 tyrosine phosphorylation ([[ pIRS-1 ]]) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."". Can you identify the relation? upregulator Consider the text ""On the basis of our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxification of << arylhydroxylamine >> carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R) and cytochrome b5 ([[ cyt b5 ]])."". Can you identify the relation? substrate Consider the text ""The beta-adrenergic/<< 5-HT1A >> receptor antagonist [[ (+/-)pindolol ]] and the selective 5-HT1B/D antagonist GR127935 produced no significant augmentation of venlafaxine-induced changes in either 5-HT or NA."". Can you identify the relation? antagonist Consider the text ""Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and [[ AM4054 ]] [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia."". Can you identify the relation? agonist Consider the text ""<< PP242 >>-induced reversal of [[ deptor ]] suppression by TGFβ was associated with a significant inhibition of TGFβ-stimulated protein synthesis and hypertrophy."". Can you identify the relation? activator Consider the text ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in << MSG >>-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased [[ pIR ]] by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."". Can you identify the relation? downregulator Consider the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."". Can you identify the relation? substrate_product-of Consider the text ""If the effectors were added after 5 min of aging they increased the activity of << soman >>-inhibited [[ AChE ]], but to a considerably smaller extent than HI 6."". Can you identify the relation? inhibitor Consider the text ""<< Nobiletin >> attenuates metastasis via both [[ ERK ]] and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 436,"RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Query: What is the relation? agonist-activator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, [[ c-Myc ]], and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. Query: What is the relation? downregulator To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance. Query: What is the relation? upregulator Stable ABCC1, << ABCC2 >> and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and ABCC2 the apical excretion of [[ BPDE glutathione ]] conjugates. Query: What is the relation? substrate The efficacy of << astemizole >>, a new, long acting, oral [[ histamine H1-receptor ]] antagonist was compared to placebo for the treatment of allergic rhinitis and conjunctivitis during the grass pollen season of 1982. Query: What is the relation? antagonist Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that << artemisinic acid >> regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the [[ hydroxymethylglutaryl CoA (HMG CoA) reductase ]] gene, which was mediated through reduced expression of the CCAAT/enhancer-binding protein (C/EBP) α gene. Query: What is the relation? indirect-downregulator Both BRL and << SAL >> produced a significant increase in postural finger tremor in keeping with [[ beta 2-adrenoceptor ]] stimulation, and this response was totally abolished by pretreatment with N20. Query: What is the relation? activator Moreover, the rank order for potency in inhibiting << acetylcholinesterase >> (ambenonium>[[ neostigmine ]]=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent. Query: What is the relation? inhibitor << GPxs >> reduce hydroperoxides to the corresponding [[ alcohols ]] by means of glutathione (GSH). Query: What is the relation? product-of Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor In addition, << Silibinin >> caused an increase in [[ p53 ]] and p21 protein level as well as mRNA levels. Query: What is the relation? indirect-upregulator The << A2A adenosine receptor >> agonist [[ CGS21680 ]] (C23H29N7O6.HCl.xH2O) (0.001-0.1 μM) did not alter NE oxidation currents. Query: What is the relation? agonist Interestingly, << AdOx >> disrupted [[ actin ]] cytoskeleton structures, leading to morphological changes, and suppressed the formation of a signaling complex composed of Src and p85/PI3K, which is linked to various tumorigenic responses. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 437,"Question: What is the relation in the sentence ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively.""? upregulator Question: What is the relation in the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol.""? agonist-activator Question: What is the relation in the sentence ""The estrogenic agent 3 beta,5 alpha-NET and << estradiol >> at a dose of 1.0 mg also inhibited the [[ UG ]] gene expression induced by P4.""? indirect-downregulator Question: What is the relation in the sentence ""<< Adenosine >> and N(6)-cyclopentyl-adenosine (CPA, [[ A1R ]] agonist) constricted MVs but not MAs.""? agonist Question: What is the relation in the sentence ""<< DBDCT >> up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of Bax/[[ Bcl-2 ]].""? indirect-upregulator Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of << fisetin >> on [[ mTOR ]].""? downregulator Question: What is the relation in the sentence ""<< Cytochrome P450 epoxygenase 2J2 >> (CYP2J2) metabolizes arachidonic acids to form [[ epoxyeicosatrienoic acids ]] (EETs), which possess various beneficial effects on the cardiovascular system.""? product-of Question: What is the relation in the sentence ""We conclude that << alprenolol >> and BAAM are competitive slowly reversible [[ beta 1-adrenoceptor ]] antagonists on rat left atria.""? antagonist Question: What is the relation in the sentence ""The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), [[ 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines ]] (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described.""? inhibitor Question: What is the relation in the sentence ""Interestingly, the allele of PRO1 was shown to enhance the activities of << gamma-glutamyl kinase >> and gamma-glutamyl phosphate reductase, both of which catalyze the first two steps of L-proline synthesis from [[ L-glutamate ]] and which together may form a complex in vivo.""? substrate Question: What is the relation in the sentence ""Subsequent analysis revealed that << cucurbitacin I >> strongly activates [[ RhoA ]] and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers.""? activator Question: What is the relation in the sentence ""We find that FP causes a decrease in stimulated eosinophil secretion of << LTC4 >> that is regulated by [[ phospholipase A2 ]] (PLA2).""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 438,"Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""Furthermore, << PTE >> treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of [[ STAT3 ]]."". Can you identify the relation? indirect-downregulator Consider the text ""Finally, the amounts of << RORalpha >> and cAspAT mRNAs were similarly increased by [[ TZD ]] treatment of human adipose tissue explants, confirming coordinated regulation."". Can you identify the relation? indirect-upregulator Consider the text ""Sorafenib (<< BAY 43-9006 >>, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases [[ VEGFR ]]/PDGFR in tumor vasculature."". Can you identify the relation? inhibitor Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""The effect was counteracted by the << D(2) >> antagonist [[ eticlopride ]], pertussis toxin, the inhibitor of intracellular Ca(2+) release TMB-8, incubation in Ca(2+)-free experimental medium, and PKC desensitization obtained by chronic pretreatment with the phorbol ester TPA."". Can you identify the relation? antagonist Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of [[ p21 ]](WAF1/CIP1) and p53."". Can you identify the relation? upregulator Consider the text ""In the current study, we reveal the inhibitory effects of baicalin on the metabolism of << dextromethorphan >> (DXM), a dual probe substrate of [[ CYP2D ]] and CYP3A, in rats."". Can you identify the relation? substrate Consider the text ""However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]]."". Can you identify the relation? activator Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (ramelteon, << TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice."". Can you identify the relation? agonist Consider the text ""<< Uridine 5'-diphosphate- glucuronosyltransferases >> are colocalized with carboxylesterases and have the potential to further metabolize carboxylic acids to [[ acyl glucuronides ]], but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases."". Can you identify the relation? product-of Consider the text ""The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in << MSG >>-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased [[ pIR ]] by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."". Can you identify the relation? downregulator Consider the text ""These findings suggest that << NFD >> inhibited the [[ EGF ]]-induced invasion and migration of MDA-MB-231 cells via EGFR-dependent PI3K/Akt signaling, leading to the down-regulation of MMP-9 expression."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 439,"Thus, it can be suggested that the inhibitory action of ginseng saponins against the immobilization stress-induced increase of plasma IL-6 level would be in periphery; at least in part, mediated by blocking << norepinephrine >>- and/or epinephrine-induced increase of [[ IL-6 ]] level in macrophage rather than in the brain. Query: What is the relation? indirect-upregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator << ABCA1 >> mediates the efflux of unesterified [[ cholesterol ]] and phospholipids from cells to lipid-poor apolipoprotein A-I (apoA-I). Query: What is the relation? substrate Previously, we showed that the << human kappa-opioid receptor >> (hkor) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged [[ U50,488H ]] treatment. Query: What is the relation? downregulator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor This study explored whether << curcumin >> improves colonic inflammation in a rat colitis model through inhibition of the TLR4/NF-κB signaling pathway and [[ IL-27 ]] expression. Query: What is the relation? indirect-downregulator << Aldosterone >> also induces the rapid phosphorylation of [[ Protein Kinase D1 ]] (PKD1). Query: What is the relation? activator 2-(2-Aminoethyl)-quinoline (<< D-1997 >>): a novel agonist at [[ 5-hydroxytryptamine1-like receptors ]] in the canine basilar artery. Query: What is the relation? agonist << Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line. Query: What is the relation? upregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of The anti-inflammatory actions of << curcumin >> on colitis may involve inhibition of the [[ TLR4 ]]/NF-κB signaling pathway and of IL-27 expression. Query: What is the relation? inhibitor CPT I (<< carnitine palmitoyltransferase I >>) catalyses the conversion of palmitoyl-CoA into [[ palmitoylcarnitine ]] in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria. Query: What is the relation? product-of The << alpha(1)-adrenoceptor >> antagonist, [[ tamsulosin ]], is selective for alpha(1A)- and alpha(1D)- over alpha(1B)-adrenoceptors. Query: What is the relation? antagonist EGTA and << 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid tetrakis >> (BAPTA), two Ca2+ chelators, but not nifedipine, an L-type Ca2+ channel blocker, prevented [[ GRIP1 ]] degradation. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",6,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",upregulator 440,"<< Nitrogen >>-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and [[ Bim ]]-mediated activation of the intrinsic apoptotic pathway. what is the relation? activator We found that reduction of the carcinogenic hydroxylamines of the aromatic amine << 4-aminobiphenyl >> (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]. what is the relation? substrate Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors. what is the relation? antagonist The results demonstrated that intracerebral infusions of << LTD4 >> (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and Aβ1-42 in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of [[ amyloid precursor protein ]] (APP). what is the relation? indirect-upregulator Systemic administration of << beta2-adrenoceptor >> agonists, [[ formoterol ]] and salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses. what is the relation? agonist The parent << phenol >> of this compound inhibits [[ aromatase ]] with an IC50 value of 0.028 nM in the same assay. what is the relation? inhibitor In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor The primary aim of these studies was to test the hypothesis that << HSD11B1 >>-derived [[ cortisol ]] has a biological role in endometrial function and conceptus development during early pregnancy in sheep. what is the relation? product-of The positive correlation between << vitamin A >> and [[ immunoglobulin A ]] concentrations might be the result of the vitamin A inductive effect during immunoglobulins A synthesis. what is the relation? upregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). what is the relation? substrate_product-of Results showed that neonatal quinpirole treatment induced << D2 >> priming that was eliminated by [[ olanzapine ]] treatment. what is the relation? indirect-downregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. what is the relation? agonist-activator Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms. what is the relation? downregulator Irbesartan (Aprovel, Avapro, Irbetan, << Karvea >>), an [[ angiotensin II receptor type 1 ]] antagonist, is approved in many countries worldwide for the treatment of hypertension. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 441,"Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""Doses of dimethocaine (1.7 mg/kg) and cocaine (0.3 mg/kg) which produced full (> 80%) substitution for cocaine were administered in combination with the << dopamine D1 receptor >> antagonist SCH 39166 ([[ (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo [d]naphtho-(2,1-b)azepine ]]) and the dopamine D2 receptor antagonist raclopride (both at 0.003-0.03 mg/kg)."", what is the relation? antagonist Regarding the sentence ""Subsequent analysis revealed that << cucurbitacin I >> strongly activates [[ RhoA ]] and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers."", what is the relation? activator Regarding the sentence ""In relation to zinc bioavailability, α-CPPs, β-CPPs, << α(s1)-CN >>(64-74)4P and β-CN(1-25)4P increased [[ zinc ]] uptake."", what is the relation? substrate Regarding the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21([[ WAF1 ]]/CIP1) and p53."", what is the relation? upregulator Regarding the sentence ""There is, however, much information on the direct (acute and chronic) effects of << alcohol >> on the binding properties of opioid receptors, as well as modulation of opioid peptide synthesis and secretion (e.g. a suggested increase in [[ beta-endorphin ]] release)."", what is the relation? indirect-upregulator Regarding the sentence ""Dexamethasone (DEX), betamethasone (<< BM >>), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]."", what is the relation? agonist Regarding the sentence ""<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive [[ oxygen ]] species (ROS), which are capable of initiating and promoting carcinogenesis."", what is the relation? product-of Regarding the sentence ""However, after 12h << CdCl2 >> treatment, cell viability diminished in 50%, accompanied by a drastic decrease of [[ metallothionein-II ]] production, and an increase in p53 activation and the pro-apoptotic protein Bax."", what is the relation? downregulator Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""There was no significant difference in TLR4, NF-κB, and << IL-27 >> mRNA and proteins between curcumin-treated and [[ sulfasalazine ]]-treated groups."", what is the relation? indirect-downregulator Regarding the sentence ""Apolipoprotein E3 (apoE3) safeguards pig proximal tubular LLC-PK1 cells against reduction in << SGLT1 >> activity induced by [[ gentamicin C ]]."", what is the relation? inhibitor Regarding the sentence ""The aim of this study was, therefore, to provide comparative binding characteristics of agonists (epinephrine, norepinephrine, isoproterenol, fenoterol, salbutamol, salmeterol, terbutalin, formoterol, broxaterol) and antagonists (propranolol, alprenolol, atenolol, metoprolol, bisoprolol, carvedilol, pindolol, BRL 37344, CGP 20712, SR 59230A, << CGP 12177 >>, ICI 118551) at all three subtypes of [[ human beta-adrenergic receptors ]] in an identical cellular background."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 442,"Given the text ""CONCLUSION: A long-term intake of << ethanol >> solution down-regulates the phosphorylation of [[ CREB ]] in the nucleus accumbens, and those changes can be reversed by naloxone, which may be one kind of the molecular mechanisms associated with ethanol dependence."", describe the relation. downregulator Given the text ""<< Ca(v)1.3 >> channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to [[ dihydropyridine ]] (DHP) L-VGCC antagonists."", describe the relation. inhibitor Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""This surprising correlation between the lack of OTC expression and sensitivity of ASS-positive HCC cells shows that OTC-deficient HCCs are sensitive to << rhArg >>-mediated [[ arginine ]] depletion."", describe the relation. substrate Given the text ""<< Phospholipase A2 >> inhibitors [[ p-bromophenacyl bromide ]] and arachidonyl trifluoromethyl ketone suppressed interleukin-2 (IL-2) expression in murine primary splenocytes."", describe the relation. activator Given the text ""8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor [[ bisindolylmaleimide I ]] (1 μM)."", describe the relation. indirect-upregulator Given the text ""It is concluded that labetalol and << dilevalol >> are [[ beta 1-adrenoceptor ]] selective antagonists."", describe the relation. antagonist Given the text ""These results show that << olanzapine >> eliminates [[ D2 receptor ]] priming and cognitive impairment and also alleviates decreases in neurotrophins and acetylcholinergic markers produced by D2 priming in the hippocampus."", describe the relation. indirect-downregulator Given the text ""<< Mouse brain serine racemase >> catalyzes specific elimination of L-serine to [[ pyruvate ]]."", describe the relation. product-of Given the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", describe the relation. agonist-activator Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""Endothelium-dependent relaxations, nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF)-type, were studied in rabbit iliac artery and aortic rings using the << G protein-coupled receptor >> agonist acetylcholine ([[ ACh ]]) and by cyclopiazonic acid (CPA), which promotes store-operated Ca(2+) entry by inhibiting the endothelial SERCA pump."", describe the relation. agonist Given the text ""CYP1A1 and << CYP1A2 >> mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."", describe the relation. upregulator Given the text ""Treatment of head and neck squamous carcinoma cells with clinically relevant concentrations of << imatinib >>-induced changes in cell morphology and growth similar to changes associated with epidermal growth factor receptor ([[ EGFR ]]) activation."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 443,"Regarding the sentence ""OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting << alpha2 adrenergic receptor >> (AR) agonist ([[ dexmedetomidine ]])."", what is the relation? agonist Regarding the sentence ""Furthermore, treatment with spironoclactone not only attenuated the pro-apoptotic effect of ALD but reversed the << ALD >>-induced increase of calpain and [[ AIF ]] levels."", what is the relation? indirect-upregulator Regarding the sentence ""Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512)."", what is the relation? upregulator Regarding the sentence ""Thus, the << NF-κB >> signaling pathway can be activated after [[ TCDD ]] treatment."", what is the relation? activator Regarding the sentence ""The molecular mechanism studies suggested that << neoechinulin A >> may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and [[ p50 ]] subunits."", what is the relation? indirect-downregulator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""This observation suggests that << MDMA >>-induced reductions in [[ SERT ]] density do not represent neuroadaptive responses to decreased levels of brain serotonin, but may occur in response to some other stimulus or to the neurotoxic effects of MDMA."", what is the relation? downregulator Regarding the sentence ""During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and << cortisol >> via hydroxysteroid (11-β) dehydrogenase 1 ([[ HSD11B1 ]])."", what is the relation? product-of Regarding the sentence ""<< [6]-Gingerol >> derived from Zingiber officinale Roscoe (ginger) was identified as a novel [[ angiotensin II type 1 receptor ]] antagonist, with an IC50 value of 8.173 µM."", what is the relation? antagonist Regarding the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam ([[ MDZ ]]) as an inducer and a substrate to CYP3A, respectively."", what is the relation? substrate Regarding the sentence ""Dasatinib (<< BMS-354825 >>) is a novel orally bioavailable [[ SRC ]]/ABL inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML)."", what is the relation? inhibitor Regarding the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Activation of << Atp8a1 >> is also reduced by these modifications; phosphatidylserine-O-methyl ester, lysophosphatidylserine, glycerophosphoserine, and [[ phosphoserine ]], which are not transported by the plasma membrane flippase, do not activate Atp8a1."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 444,"In reference to ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""In vitro studies, however, revealed that << EO >> inhibits [[ fibrin ]] clot formation because of the Ca2+-chelating ability of its constituent ethanolamine, although oleate or benzyl alcohol exhibited procoagulant activity in FPA formation in vitro."", what is the relation? inhibitor In reference to ""Firstly, transgenic plants overexpressing formate dehydrogenase (FDH, EC 1.2.1.2) were used to continue our previous studies on the function of << FDH >> in [[ formate ]] metabolism."", what is the relation? substrate In reference to ""<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, [[ glycosylated hemoglobin ]] (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin."", what is the relation? indirect-downregulator In reference to ""Adenosine and N(6)-cyclopentyl-adenosine (<< CPA >>, [[ A1R ]] agonist) constricted MVs but not MAs."", what is the relation? agonist In reference to ""Under isotonic conditions, N-ethylmaleimide (<< NEM >>) produced [[ KCC ]] activation and transient cell shrinkage."", what is the relation? activator In reference to ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of VEGFand [[ MMP-9 ]], resulting from the inhibition of Akt pathway."", what is the relation? downregulator In reference to ""Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512)."", what is the relation? upregulator In reference to ""Favorable enzyme profiles (high TP and low << DPD >>) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS."", what is the relation? product-of In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""Cotreatments of 5, 10 and 20 µg/mL concentrations of MEP with << aflatoxin B(1) >> decreased the frequencies of SCE and the malondialdehyde level and increased amount of [[ superoxide dismutase ]], glutathione and glutathione peroxidase which were decreased by aflatoxin."", what is the relation? indirect-upregulator In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""In the rabbit pulmonary artery, rilmenidine and << oxymetazoline >> are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan."", what is the relation? antagonist In reference to ""Through immunoblotting analysis, it was found that << AdOx >> was capable of indirectly diminishing the phosphorylation of oncogenic [[ Src ]] and its kinase activity."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 445,"Question: What is the relation in the sentence ""Colonic cyclooxygenase-2 and interkeukin-1beta mRNA and spinal << c-FOS >> mRNA expression were significantly down-regulated by [[ ATB-429 ]], but not by mesalamine.""? indirect-downregulator Question: What is the relation in the sentence ""Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction and may be related to limited availability of << L-arginine >>, the common substrate of [[ constitutive nitric-oxide synthase ]] (NOS) and cytosolic arginase I and mitochondrial arginase II.""? substrate Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""Our previous work, built on the early pioneering multikinase inhibitor << LY294002 >>, resulted in the only [[ PI3K ]] vascular-targeted PI3K inhibitor prodrug, SF1126, which has now completed Phase I clinical trials.""? inhibitor Question: What is the relation in the sentence ""<< Thalidomide >> reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased [[ cytochrome c ]], but had no effect on that of COX-1, in MCF-7 and HL-60.""? indirect-upregulator Question: What is the relation in the sentence ""Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration.""? upregulator Question: What is the relation in the sentence ""The inhibitory effect of endothelin-1 on the contraction induced by 5-HT is abolished by deendothelialization, by the << endothelin ET(B) receptor >> antagonist [[ RES 701-1 ]], by indomethacin, or by glibenclamide.""? antagonist Question: What is the relation in the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA.""? substrate_product-of Question: What is the relation in the sentence ""These results suggest that the pro-inflammatory effect of << H(2)S >> may be mediated by [[ SP ]]-NK-1R related pathway in mouse pancreatic acinar cells.""? product-of Question: What is the relation in the sentence ""Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [[[ 9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol ]]], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia.""? agonist Question: What is the relation in the sentence ""A prerequisite for this hypothesis was the unproved assumption that rabbit and human << alpha(2A)-adrenoceptors >> are equally activated by [[ rilmenidine ]].""? activator Question: What is the relation in the sentence ""The results suggest that the suppression of << TLR4 >> activity by auranofin may be the molecular mechanism through which [[ auranofin ]] exerts anti-rheumatic activity.""? downregulator Question: What is the relation in the sentence ""The ability of << sorafenib >> to inhibit oncogenic PDGFRbeta and [[ FLT3 ]] mutants and overcome resistance to other small molecule inhibitors.""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 446,"<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Please explain the relation. agonist-activator Five classes of chalcogenopyrylium dyes (CGPs) were examined for their ability to modulate transport of [(3)H]estradiol glucuronide (<< E217βG >>) (a prototypical [[ MRP ]] substrate) into MRP-enriched inside-out membrane vesicles. Please explain the relation. substrate Further, << 5HHMF >> increased specific DNA-binding activity of Nrf2, and transient knockdown with [[ Nrf2 ]] siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity. Please explain the relation. upregulator Uridine 5'-diphosphate- glucuronosyltransferases are colocalized with << carboxylesterases >> and have the potential to further metabolize carboxylic acids to [[ acyl glucuronides ]], but it is currently unknown if acyl glucuronides, being esters, also interact with carboxylesterases. Please explain the relation. product-of Specifically, aniracetam, which potentiates wild-type AMPA receptors, is ineffective on the non-desensitizing << GluR3 >>(L507Y) mutant, but has synergistic effects with [[ lithium ]] on wild-type receptors. Please explain the relation. activator The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, [[ glutamate synthase ]], and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings. Please explain the relation. downregulator Type I deiodinase, liver fatty-acid binding protein and << cytochrome P450 (CYP) 3A37 >> mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1. Please explain the relation. indirect-upregulator Pregnane X Receptor Mediates Dyslipidemia Induced by the << HIV Protease >> Inhibitor [[ Amprenavir ]] in Mice. Please explain the relation. inhibitor The involvement of EP1 and << EP2 receptors >> is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist [[ butaprost ]] (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Please explain the relation. agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of Moreover, protein and mRNA levels of DSS-induced proinflammatory cytokines in colon, including TNF-α, IL-1β, IL-18, IL-17A and << IFN-γ >>, were markedly suppressed by [[ Fc11a-2 ]]. Please explain the relation. indirect-downregulator << (+)-Tamsulosin >>, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]. Please explain the relation. antagonist Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor Opening of << Panx1 >> HCs during repetitive activation allows efflux of [[ ATP ]], influx of glucose and possibly Ca(2+) too, which are required for potentiation of contraction. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 447,"Since << gemfibrozil >> is known to activate [[ peroxisome proliferator-activated receptor-alpha ]] (PPAR-alpha), we investigated the role of PPAR-alpha in gemfibrozil-mediated inhibition of iNOS. Query: What is the relation? activator CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme. Query: What is the relation? upregulator << Pinosylvin >> was also found to attenuate the activation of proteins involved in focal adhesion kinase (FAK)/c-Src/extracellular signal-regulated kinase (ERK) signaling, and phosphoinositide 3-kinase (PI3K)/Akt/ glycogen synthase kinase 3β ([[ GSK-3β ]]) signaling pathway. Query: What is the relation? indirect-downregulator Exposure to << PAHs >>, their metabolites, and ROS further increase [[ AKRs ]] isoform expression that may amplify oxidative damage. Query: What is the relation? indirect-upregulator Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective << alpha(1D)-adrenoceptor >> antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively). Query: What is the relation? agonist In this report, we show that the hypolipidemic agent << atorvastatin >> is a competitive inhibitor of [[ porcine DPP-IV ]] in vitro, with K(i)=57.8+/-2.3 microM. Query: What is the relation? inhibitor Since the original discovery of << azoles >> analogs as PXR antagonists, we have preliminarily defined an important [[ PXR ]] antagonist pharmacophore and developed less-toxic PXR antagonists. Query: What is the relation? antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15). Query: What is the relation? substrate_product-of When cultured in liquid minimal medium, yeast cells expressing the mutated << gamma-glutamyl kinase >> were found to accumulate intracellular [[ L-proline ]] and showed a prominent increase in cell viability after freezing at -20 degrees C compared to the viability of cells harboring the wild-type PRO1 gene. Query: What is the relation? product-of Several active analogues were also evaluated for their ability to block uptake of << DA >>, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-[[ hDAT ]], HEK-hSERT, and HEK-hNET cells. Query: What is the relation? substrate RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Query: What is the relation? agonist-activator Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]. Query: What is the relation? downregulator Inhibitors and neutralizing antibodies against heparin-binding epidermal growth factor-like growth factor (HB-EGF), and to a lesser extent transforming growth factor-alpha, reduced << imatinib >>-mediated [[ mitogen activated protein kinase ]] (MAPK) activation. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 448,"In reference to ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", what is the relation? upregulator In reference to ""These actions are consistent with a pre-junctional inhibition of neuropeptide release from perivascular afferents of the trigeminal nerve, as confirmed by independent studies showing that << zolmitriptan >> blocks elevations of [[ calcitonin-gene-related peptide ]] in jugular venous blood during electrical stimulation of the trigeminal ganglion."", what is the relation? indirect-downregulator In reference to ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator In reference to ""In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the << CB2 >> antagonist AM630 [[[ (6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone) ]]]."", what is the relation? antagonist In reference to ""At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of GluN1/[[ GluN2B ]] receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic."", what is the relation? downregulator In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""To this end, 158N murine oligodendrocytes were treated with 7KC or << 7βOHC >> inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving [[ Mcl-1 ]], and caspase-3 activation."", what is the relation? activator In reference to ""Glycylsarcosine coadministration could inhibit the uptake of << cefadroxil >> in [[ PEPT2 ]](+/+) mice (p < 0.01) but not PEPT2(-/-) mice."", what is the relation? substrate In reference to ""Aldose reductase (<< AR >>) catalyzes the reduction of toxic lipid aldehydes to their [[ alcohol ]] products and mediates inflammatory signals triggered by lipopolysaccharide (LPS)."", what is the relation? product-of In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""The cytosine analog 5-aza-2'-deoxycytidine (<< decitabine >>) hypomethylates DNA by inhibiting [[ DNA methyltransferase ]]."", what is the relation? inhibitor In reference to ""The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the << adenosine A3 receptor >> agonist [[ IB-MECA ]] (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0.75 mg/kg b.w."", what is the relation? agonist In reference to ""The activation may be accelerated by an acute inflammatory process provoked by << oleate >>, which is supported by such clinical manifestations as mild fever, retrosternal pain leukocytosis and an increase in plasma [[ fibrinogen ]] level which was observed in all during the period."", what is the relation? indirect-upregulator In reference to ""In this work a novel approach combining HPLC-UV on-line with oaTOF-MS and ICPMS was applied to investigate in human and rat plasma the metabolism of labelled BK (79/81 Br-Phe5) BrBK in the presence of two new dual ACE/<< NEP >> inhibitors (GW660511X and [[ omapatrilat ]]) currently under clinical trial."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 449,"Consider the text ""The results suggested that both the EtOAc extract and berberine were able to activate PPARα/β/γ, and Rhizoma Coptis contains potential natural agonists of << PPARs >> besides [[ berberine ]]."". Can you identify the relation? agonist Consider the text ""<< PTE >> also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins ([[ Bax ]], Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27."". Can you identify the relation? indirect-upregulator Consider the text ""Moreover, BH(4) treatment of the << fructose >>-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and [[ activating protein-1 ]], which were increased in fructose-fed rats."". Can you identify the relation? upregulator Consider the text ""<< HSYA >> treatment also decreased NF-κB [[ p65 ]] nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK)."". Can you identify the relation? downregulator Consider the text ""Collectively, these results suggest that inhibition of << mTORC1 >> signaling by [[ fisetin ]] prevents adipocyte differentiation of 3T3-L1 preadipocytes and obesity in HFD-fed mice."". Can you identify the relation? inhibitor Consider the text ""<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O-methyltransferase ([[ COMT ]])."". Can you identify the relation? substrate Consider the text ""Pharmacological properties of << lorglumide >> as a member of a new class of [[ cholecystokinin ]] antagonists."". Can you identify the relation? antagonist Consider the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."". Can you identify the relation? agonist-activator Consider the text ""Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, [[ thymidine kinase-1 ]] and thymidylate synthase, in various types of cancer."". Can you identify the relation? product-of Consider the text ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using [[ dexamethasone 21-phosphate ]] (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively."". Can you identify the relation? activator Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Ginseng total saponins, << ginsenosides Rb2, Rg1 and Rd >> administered intraperitoneally attenuated the immobilization stress-induced increase in plasma [[ IL-6 ]] level."". Can you identify the relation? indirect-downregulator Consider the text ""RESULT(S): The expression of endometrial ERalpha, << PRAB >>, PRB, and SRC-1 was increased significantly after 1 week of [[ mifepristone ]], but the increase was no longer seen after 10 weeks."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 450,"<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of Histamine and << Ca >> added to NSAIDs amplified the activating effect of the latter on [[ CA II ]]. what is the relation? upregulator To determine whether << 3,4-methylenedioxymethamphetamine >> (MDMA)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured. what is the relation? downregulator Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], [[ AM2389 ]] [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia. what is the relation? agonist Enzyme kinetic analyses using human liver microsomes revealed inhibition of << CYP1A1 >> activity by delphinidin (IC50 78 μM) and [[ pelargonidin ]] (IC50 33 μM). what is the relation? inhibitor In further evaluation, the representative compound << N,N-diethyl-N-(2-(N-methyltetradecanamido)ethyl)prop-2-en-1-aminium bromide >> (3b) exhibited potent pro-apoptotic activity, through [[ RhoB ]] activation, in HeLa cells. what is the relation? activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor Carnitine acetyltransferases (<< CrAT >>) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. what is the relation? substrate Ginseng total saponins, << ginsenosides Rb2, Rg1 and Rd >> administered intraperitoneally attenuated the immobilization stress-induced increase in plasma [[ IL-6 ]] level. what is the relation? indirect-downregulator << ACTH >>-stimulated peak cortisol, delta cortisol, and [[ delta DHEA ]]-S levels are decreased during hyperthyroidism, probably due to increased turnover. what is the relation? product-of Selective antagonism of << GluR5 >> kainate-receptor-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons. what is the relation? antagonist The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. what is the relation? agonist-activator In addition, the number and area of glutathione S-transferase placental form (GST-P) positive foci and << proliferating cell nuclear antigen >> (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg [[ MEG ]] compared with the control animals. what is the relation? indirect-upregulator Cytosolic [AMP] reported metabolically active << AMP >>, which triggered increased [[ AMPK ]] activity, but measures of total AMP did not. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 451,"These results suggest that prostacyclin may play a role in downregulating << tissue factor >> expression in monocytes, at least in part via elevation of intracellular levels of [[ cyclic AMP ]]. Question: what is the relation? Answer: downregulator Dexamethasone (DXM) decreased the expression of CXCL-8, VEGF, and iNOS induced by reIL-4, while 1400W dihydrochloride (<< 1400W >>), a selective inhibitor of iNOS, decreased the expression of E-selectin, VEGF, and [[ iNOS ]]. Question: what is the relation? Answer: indirect-downregulator These results suggest that ACS1 and << ACS4 >> may be linked to [[ triacylglycerol ]] synthesis. Question: what is the relation? Answer: product-of These observations suggest that uptake of << phenformin >> into liver mitochondria is at least partly mediated by OCTN1 and functionally relevant to its inhibition potential of [[ complex I ]] respiration. Question: what is the relation? Answer: inhibitor In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor << Cat-1 >>, the transporter for the essential amino acids, arginine and [[ lysine ]], is one of the up-regulated genes. Question: what is the relation? Answer: substrate The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Question: what is the relation? Answer: agonist-activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Question: what is the relation? Answer: substrate_product-of << CDCA >> induced dose-dependent expression of Cdx2 and [[ MUC2 ]] at both the mRNA and protein levels. Question: what is the relation? Answer: indirect-upregulator << AChE >> was easier reactivated after [[ paraoxon ]] treatment. Question: what is the relation? Answer: activator Analysis of splice variants and site-directed mutants of the AMPA receptor GluR3 expressed in Xenopus oocytes has shown that lithium produces a large potentiation of the << GluR3 flop >> splice variant and suggested that [[ lithium ]] might inhibit rapid desensitization, which is characteristic of this receptor (Karkanias, N. and Papke, R., Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol., 81 (1999) 1506-1512). Question: what is the relation? Answer: upregulator Since the original discovery of << azoles >> analogs as [[ PXR ]] antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic PXR antagonists. Question: what is the relation? Answer: antagonist The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity. Question: what is the relation? Answer: agonist Non-steroidal anti-inflammatory drugs (NSAIDs) are competitive inhibitors of << cyclooxygenase >> (COX), the enzyme that mediates biosynthesis of prostaglandins and [[ thromboxanes ]] from arachidonic acid. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 452,"Given the text ""We found that reduction of the carcinogenic hydroxylamines of the aromatic amine << 4-aminobiphenyl >> (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]."", describe the relation. substrate Given the text ""The results showed that IR tyrosine phosphorylation (<< pIR >>) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased pIR by 76 % in [[ MSG ]] mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.)."", describe the relation. downregulator Given the text ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % ([[ MSG ]], 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; MSG, 22.2 ± 1.1 a.u.)."", describe the relation. upregulator Given the text ""We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (<< CDCA >>)-induced expression of [[ Cdx2 ]] and MUC2 in normal rat gastric epithelial cells (RGM-1 cells)."", describe the relation. indirect-upregulator Given the text ""Effect of << (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide >> (ramelteon, TAK-375), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice."", describe the relation. agonist Given the text ""Isometric contraction induced by a submaximal concentration of << Ang II >> (10(-7) mol/L) was reduced in a dose-dependent way by [[ torasemide ]] (IC(50)=0.5+/-0.04 micromol/L)."", describe the relation. inhibitor Given the text ""<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of [[ cystathionine-gamma-lyase ]] (CSE) and cystathionine-beta-synthase (CBS)."", describe the relation. product-of Given the text ""<< NaAsO(2) >> increased the mRNA levels of the light and medium subunits of neurofilament and decreased the mRNA levels of tau and [[ tubulin ]] in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin."", describe the relation. indirect-downregulator Given the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the [[ Cyp1a1 ]], Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", describe the relation. activator Given the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", describe the relation. agonist-activator Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""Ca(v)1.3 channels were less sensitive to pentobarbital inhibition than Ca(v)1.2 channels, similar to dihydropyridine (<< DHP >>) [[ L-VGCC ]] antagonists."", describe the relation. antagonist Given the text ""RESULTS: NF-kappaB/<< Rel >> activity induced by tumor necrosis factor alpha, 12-O-tetradecanoylphorbol-13-acetate, or overexpression of NF-kappaB-inducing kinase, IKK-alpha, IKK-beta, or constitutively active IKK-alpha and IKK-beta mutants was inhibited dose dependently by [[ sulfasalazine ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 453,"Consider the text ""In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the << CB2 >> antagonist AM630 [[[ (6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone) ]]]."". Can you identify the relation? antagonist Consider the text ""Suppression of << Src >>/ERK and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells."". Can you identify the relation? downregulator Consider the text ""<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and [[ receptor for AGE ]] (RAGE)."". Can you identify the relation? indirect-downregulator Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Third, << ABCA1 >>-RNAi suppressed hepatic [[ alpha-tocopherol ]] secretion."". Can you identify the relation? product-of Consider the text ""Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα ([[ IκBα ]]) kinase, and inositol requiring enzyme 1α."". Can you identify the relation? activator Consider the text ""The channel activators << avermectin >> and moxidectin usually retain their inhibitory potency in the [[ Rdl ]] subunit mutants."". Can you identify the relation? inhibitor Consider the text ""CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme."". Can you identify the relation? upregulator Consider the text ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."". Can you identify the relation? substrate_product-of Consider the text ""<< c-fos >> expression was induced in urethane-anaesthetized rats by intracisternal [[ capsaicin ]] administration."". Can you identify the relation? indirect-upregulator Consider the text ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."". Can you identify the relation? agonist-activator Consider the text ""Stable << ABCC1 >>, ABCC2 and ABCC3 knockdown cell lines were generated, thus making it possible to demonstrate that ABCC1 mediates the basolateral and ABCC2 the apical excretion of [[ BPDE glutathione ]] conjugates."". Can you identify the relation? substrate Consider the text ""Injections of << m-CPBG >>, a selective [[ 5-HT3 ]] receptor agonist, induced a significant increase in blood glucose in non-stressed rats in both fasted and in fed states."". Can you identify the relation? agonist Consider the text ""<< Dimemorfan >> pre-treatment also attenuated the KA-induced increases in c-fos/c-jun expression, [[ activator protein (AP)-1 ]] DNA-binding activity, and loss of cells in the CA1 and CA3 fields of the hippocampus."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 454,"In reference to ""Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized << KCNK1 >> as a [[ phenobarbital ]]-inducible antihyperplasia factor."", what is the relation? activator In reference to ""Moreover, << curcumin >> alleviated [[ Sim2 ]] expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia."", what is the relation? indirect-upregulator In reference to ""The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, glutamate synthase, and [[ glutamate dehydrogenase ]], promoting amino acid conversion and protein synthesis in soybean seedlings."", what is the relation? downregulator In reference to ""We found that reduction of the carcinogenic hydroxylamines of the aromatic amine << 4-aminobiphenyl >> (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]."", what is the relation? substrate In reference to ""The kinase activity of << EGFR >> was little inhibited by [[ TT-B ]] in a cell-free system."", what is the relation? inhibitor In reference to ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""We isolated partial cDNAs that codified for enzymes implicated in the << anthocyanin >> biosynthesis such as l-phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), and an antioxidant enzyme such as [[ ascorbate peroxidase ]] (APX)."", what is the relation? product-of In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""<< D-Serine >> was previously identified in mammalian brain and was shown to be a co-agonist at the 'glycine' site of the [[ N-methyl-D-aspartate (NMDA)-type receptors ]]."", what is the relation? agonist In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, [[ doxazosin ]], prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials."", what is the relation? antagonist In reference to ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", what is the relation? upregulator In reference to ""Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/[[ GSK-3β ]] signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc."", what is the relation? indirect-downregulator In reference to ""The transcriptional activity of torafugu PPARalpha1 was enhanced 4.5- and 11.5-fold by << Wy-14643 >> and 5,8,11,14-eicosatetraynoic acid (ETYA) each at 10 microM, respectively, whereas that of [[ PPARalpha2 ]], 4.5- and 7.3-fold at the same concentration of the respective ligands, respectively."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 455,"Inhibition of angiogenesis and invasion by << DMBT >> is mediated by downregulation of VEGF and [[ MMP-9 ]] through Akt pathway in MDA-MB-231 breast cancer cells. Question: what is the relation? Answer: downregulator In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with [[ rauwolscine ]], phentolamine, and idazoxan. Question: what is the relation? Answer: antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor Furthermore, V(5+) significantly inhibited the << TCDD >>-induced [[ AhR ]]-dependent luciferase activity. Question: what is the relation? Answer: indirect-upregulator db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and [[ carnitine acetyltransferase ]], respectively. Question: what is the relation? Answer: upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. Question: what is the relation? Answer: agonist-activator In addition, << 5HHMF >> blocked LPS-induced phosphorylation of [[ IκB ]], resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression. Question: what is the relation? Answer: inhibitor The mRNA levels of << microphthalmia-associated transcription factor >> (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment. Question: what is the relation? Answer: indirect-downregulator Prazosin (nonselective << alpha(1)-adrenoceptor >> antagonist), silodosin (selective alpha(1A)-adrenoceptor antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively). Question: what is the relation? Answer: agonist Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of << NO >> and the expression of [[ inducible nitric-oxide synthase ]] (iNOS) in human U373MG astroglial cells and primary astrocytes. Question: what is the relation? Answer: product-of << Amitriptyline >>, but not any other tricyclic or selective serotonin reuptake inhibitor antidepressants, promotes [[ TrkA ]] autophosphorylation in primary neurons and induces neurite outgrowth in PC12 cells. Question: what is the relation? Answer: activator Among the [Fe-S] cluster biosynthetic proteins are included a pyridoxal phosphate-dependent enzyme (<< NifS >>) that is involved in the activation of sulphur from [[ l-cysteine ]], and a molecular scaffold protein (NifU) upon which [Fe-S] cluster precursors are formed. Question: what is the relation? Answer: substrate One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of << glutamine >> to oxoglutaramic acid ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of We previously demonstrated that the somatostatinergic system, implicated in neuronal survival control, can be modulated by << α-tocopherol >> in the rat dentate gyrus, increasing [[ cyclic adenosine monophosphate response element binding protein ]] phosphorylation. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 456,"Labetalol (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the << isoprenaline >> responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors. Please explain the relation. agonist In conclusion, << fenoterol >>-induced constitutive [[ beta(2)-adrenoceptor ]] activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist timolol. Please explain the relation. activator The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (MSG, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased << pIR >> by 76 % in MSG mice without affecting control mice ([[ MSG ]], 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). Please explain the relation. downregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator In addition, << 5HHMF >> blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and [[ p50 ]], which are important molecules involved in the regulation of iNOS expression. Please explain the relation. indirect-downregulator This surprising correlation between the lack of OTC expression and sensitivity of ASS-positive HCC cells shows that OTC-deficient HCCs are sensitive to << rhArg >>-mediated [[ arginine ]] depletion. Please explain the relation. substrate In PFC, << DEX >> caused activation of AKT, augmentation of pro-survival Bcl-2 protein and enhanced Bcl-2/[[ Bax ]] protein ratio, as well Bcl-2 translocation to mitochondria. Please explain the relation. indirect-upregulator The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of << navitoclax >>, a selective inhibitor of both BCL-2 and BCL-2-like 1 ([[ BCL-X(L) ]]), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. Please explain the relation. inhibitor CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of << TCDD >> potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme. Please explain the relation. upregulator Structural features of the central cannabinoid CB1 receptor involved in the binding of the specific << CB1 >> antagonist [[ SR 141716A ]]. Please explain the relation. antagonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Please explain the relation. agonist-inhibitor The COX pathway generates inflammatory prostaglandins, while the << 5-LOX >> pathway generates inflammatory [[ leukotrienes ]]. Please explain the relation. product-of << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Please explain the relation. substrate_product-of Another inhibitor, brequinar was previously reported to be a slow-binding inhibitor of the human dihydroorotate dehydrogenase [W. Knecht, M. Loffler, Species-related inhibition of << human and rat dihyroorotate dehydrogenase >> by immunosuppressive [[ isoxazol ]] and cinchoninic acid derivatives, Biochem. Pharmacol. 56 (1998) 1259-1264]. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 457,"Regarding the sentence ""Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the << N >>-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent [[ PDE3 ]] inhibition."", what is the relation? inhibitor Regarding the sentence ""The positive correlation between << vitamin A >> and [[ immunoglobulin A ]] concentrations might be the result of the vitamin A inductive effect during immunoglobulins A synthesis."", what is the relation? upregulator Regarding the sentence ""Tissue-type plasminogen activator (tPA), a << serine >> protease well known for generating plasmin, has been demonstrated to induce [[ matrix metalloproteinase-9 ]] (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts."", what is the relation? indirect-upregulator Regarding the sentence ""<< Thymidine kinase-1 >> (TK-1) and thymidylate synthase (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively."", what is the relation? product-of Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased [[ superoxide dismutase ]] (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control."", what is the relation? downregulator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""In the DRN, << brexpiprazole >> completely inhibited the firing of 5-HT neurons via [[ 5-HT1A ]] agonism and was more potent than aripiprazole (ED50 = 230 and 700 mug/kg, respectively)."", what is the relation? agonist Regarding the sentence ""Moreover, treatment of U937 cells with << 2-hydroxy-3-methylanthraquinone >> resulted in activation of [[ caspase-3 ]]."", what is the relation? activator Regarding the sentence ""In the rabbit pulmonary artery, rilmenidine and << oxymetazoline >> are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan."", what is the relation? antagonist Regarding the sentence ""The mRNA levels of microphthalmia-associated transcription factor (<< MITF >>) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by [[ artemisinic acid ]] treatment."", what is the relation? indirect-downregulator Regarding the sentence ""BACKGROUND AND AIMS: Glutamic acid decarboxylase (<< GAD >>, EC 4.1.1.15) catalyses the conversion of [[ glutamate ]] to gamma-aminobutyric acid (GABA)."", what is the relation? substrate Regarding the sentence ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", what is the relation? agonist-activator Regarding the sentence ""<< Toosendanin >> induces apoptosis through suppression of [[ JNK ]] signaling pathway in HL-60 cells."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 458,"One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). what is the relation? substrate_product-of In human blood, the tested glucocorticoids << beclomethasone >>, dexamethasone and fluticasone inhibited the LPS induced TNF release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced [[ TNF ]] release, with the exception of dexamethasone, was much less pronounced. what is the relation? inhibitor << Dexamethasone >> (DEX), betamethasone (BM), and their esterified-derivatives had full transrepression agonistic activity in a reporter assay using CV-1 cells transfected with either [[ human or rat GR ]]. what is the relation? agonist We observed a significant reduction in CSE induced luciferase expression, NF-κB DNA binding, << I-κBε >> degradation and c-Rel nuclear translocation in cells pretreated with [[ vitamin C ]]. what is the relation? downregulator Prostaglandin E1, E2, STA2 (a stable analogue of << thromboxane A2 >>), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit [[ HVA Ca2+ channels ]] was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. what is the relation? indirect-downregulator Clinical effects of << pranlukast >>, an oral [[ leukotriene receptor ]] antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial. what is the relation? antagonist The data show that CP[c]Ph is less potent at inducing << CYP1A >> gene expression in rainbow trout than [[ benzo[a]pyrene ]] (B[a]P), a well-known Ah-receptor agonist. what is the relation? indirect-upregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. what is the relation? agonist-activator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Also, << vinblastine >> enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of [[ apoptosis signal-regulating kinase 1 ]], c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α. what is the relation? activator << Omega class GSTs >> have dehydroascorbate reductase and thioltransferase activities and also catalyze the reduction of [[ monomethylarsonate ]], an intermediate in the pathway of arsenic biotransformation. what is the relation? substrate G6pc2 deletion resulted in a leftward shift in the dose-response curve for << glucose >>-stimulated [[ insulin ]] secretion (GSIS). what is the relation? upregulator Thymidine kinase-1 (TK-1) and thymidylate synthase (<< TS >>) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively. what is the relation? product-of Inhibitors and neutralizing antibodies against heparin-binding epidermal growth factor-like growth factor (HB-EGF), and to a lesser extent transforming growth factor-alpha, reduced << imatinib >>-mediated mitogen activated protein kinase ([[ MAPK ]]) activation. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 459,"Regarding the sentence ""Labetalol (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the << isoprenaline >> responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors."", what is the relation? agonist Regarding the sentence ""<< Jaspamide >> also inhibited other channels including Cav1.2, Cav3.2, and [[ HCN2 ]]; however, the Kv11.1 (hERG) channel was minimally affected."", what is the relation? inhibitor Regarding the sentence ""Thus, the increase in mPFC << DAT >> function was an SHR-specific long term consequence of [[ methylphenidate ]] treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration."", what is the relation? upregulator Regarding the sentence ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (<< CYP3A >>) in rats using dexamethasone 21-phosphate ([[ DEX-P ]]) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively."", what is the relation? activator Regarding the sentence ""In the current study, we reveal the inhibitory effects of baicalin on the metabolism of << dextromethorphan >> (DXM), a dual probe substrate of CYP2D and [[ CYP3A ]], in rats."", what is the relation? substrate Regarding the sentence ""In addition, << ethanol >> induced degradation of DNA methyltransferases (DNMT-1, DNMT-3a, and DNMT-3b), as well as the methyl CpG-binding proteins (MeCP-2, [[ MBD-2 ]] and MBD-3), in MEF cells by the proteasomal pathway."", what is the relation? downregulator Regarding the sentence ""<< Fisetin >> treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB [[ p65 ]] unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin."", what is the relation? indirect-downregulator Regarding the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", what is the relation? agonist-activator Regarding the sentence ""On the other hand, the accumulation of << Ser >> through the C1-THF synthase/[[ SHMT ]] pathway in glyD plants was 2.5-fold greater than that in WT plants."", what is the relation? product-of Regarding the sentence ""The hemoglobin A1c (<< HbA1c >>) of all patients improved significantly from 8.1±1.2% to 7.6±1.1% after 12 weeks of add-on therapy with [[ sitagliptin ]] (p<0.01), and the insulin dosage was reduced from 27.3±15.8 U/day to 24.5±16.5 U/day (p<0.001)."", what is the relation? indirect-upregulator Regarding the sentence ""<< Betaxolol >>, a beta(1)-adrenoceptor antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other [[ beta-adrenoceptor ]] antagonists."", what is the relation? antagonist Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Collectively, our results suggest that H(2)S can inhibit NO production and NF-kappaB activation in LPS-stimulated macrophages through a mechanism that involves the action of << HO-1 >>/[[ CO ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 460,"In reference to ""Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms."", what is the relation? downregulator In reference to ""Prazosin (nonselective alpha(1)-adrenoceptor antagonist), silodosin (selective << alpha(1A)-adrenoceptor >> antagonist) and BMY-7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist) competitively antagonized the [[ phenylephrine ]]-induced contraction (pA(2) values, 8.60+/-0.07, 9.44+/-0.06 and 5.75+/-0.07, respectively)."", what is the relation? agonist In reference to ""<< Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS)."", what is the relation? product-of In reference to ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""In the in vitro assay, << kinsenoside >> (20 and 50μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and [[ catalase ]] (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system."", what is the relation? indirect-downregulator In reference to ""We conclude that alprenolol and << BAAM >> are competitive slowly reversible [[ beta 1-adrenoceptor ]] antagonists on rat left atria."", what is the relation? antagonist In reference to ""Using the nucleoside transporter deficient PK15NTD cells stably expressing ENT1 and ENT2, it was found that << troglitazone >> inhibited [[ ENT1 ]] but had no effect on ENT2."", what is the relation? inhibitor In reference to ""<< Levodopa >> is absorbed in the small bowel and is rapidly catabolized by [[ aromatic-L-amino-acid decarboxylase ]] (AADC) and catechol-O-methyltransferase (COMT)."", what is the relation? substrate In reference to ""<< Cadmium >> activates [[ NADPH oxidase ]]."", what is the relation? activator In reference to ""Mutation of arginine 228 to << lysine >> enhances the [[ glucosyltransferase ]] activity of bovine beta-1,4-galactosyltransferase I."", what is the relation? upregulator In reference to ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""Upon co-exposure to V(5+) and TCDD, << V(5+) >> significantly potentiated the TCDD-mediated induction of the Cyp1a1, [[ Cyp1a2 ]], and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h."", what is the relation? indirect-upregulator In reference to ""The overall results indicate that << ICI >> may exert agonistic and antagonistic effects on uterine cell proliferation through differential activation of the [[ Akt ]] pathway depending on the administration period during the estrous cycle, and indicates that the mechanism of cell proliferation during the physiological conditions of the estrous cycle, is under a different and more complex regulation than in the ovariectomized +E2 animal model."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 461,"Given the text ""<< Beta-1,4-galactosyltransferase I >> (beta4Gal-T1) normally transfers Gal from [[ UDP-Gal ]] to GlcNAc in the presence of Mn(2+) ion (Gal-T activity) and also transfers Glc from UDP-Glc to GlcNAc (Glc-T activity), albeit at only 0.3% efficiency."", describe the relation. substrate Given the text ""Dietary EPA/<< DHA >> treatment restored endogenous biosynthesis of n-3 derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving [[ insulin ]] sensitivity."", describe the relation. indirect-upregulator Given the text ""Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of << fisetin >> on [[ mTOR ]]."", describe the relation. downregulator Given the text ""Synthesis, molecular modeling and evaluation of novel << N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone >> derivatives as dual inhibitors for [[ cholinesterases ]] and Aβ aggregation."", describe the relation. inhibitor Given the text ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", describe the relation. substrate_product-of Given the text ""In the present study, we identified << amprenavir >>, a widely used HIV PI, as a potent [[ PXR ]]-selective agonist."", describe the relation. agonist Given the text ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", describe the relation. agonist-inhibitor Given the text ""In the << IB-MECA >> group, [[ α-amylase ]] activity was decreased with statistically high significance compared to group I."", describe the relation. indirect-downregulator Given the text ""The latter reaction, catalyzed by aspartoacylase (<< ASPA >>), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter."", describe the relation. product-of Given the text ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport."", describe the relation. upregulator Given the text ""Thus, we found that << 5HHMF >> enhances heme oxygenase-1 (HO-1) expression via [[ nuclear factor-erythroid 2-related factor 2 ]] (Nrf2) activation."", describe the relation. activator Given the text ""Local LC citalopram effect was abolished by LC presence of the << 5-HT3 >> receptor antagonist [[ MDL72222 ]] (1 μM) but not the 5-HT1/2 receptor antagonist methiothepin (1 μM)."", describe the relation. antagonist Given the text ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", describe the relation. agonist-activator Given the text ""RESULTS: NF-kappaB/Rel activity induced by tumor necrosis factor alpha, 12-O-tetradecanoylphorbol-13-acetate, or overexpression of NF-kappaB-inducing kinase, IKK-alpha, IKK-beta, or constitutively active << IKK-alpha >> and IKK-beta mutants was inhibited dose dependently by [[ sulfasalazine ]]."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 462,"Regarding ""The upregulation of << calpain >>, tBid and caspase-3 activity were further inhibited by treatment with EGTA in the presence of [[ ALD ]]."", can you determine the relation? indirect-upregulator Regarding ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", can you determine the relation? agonist-activator Regarding ""RESULTS: << Indomethacin >>, in vitro and in vivo. induces an increase in erythorcyte CA I and [[ CA II ]] activity."", can you determine the relation? activator Regarding ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein ([[ pRb ]]), and the upregulation of p21(WAF1/CIP1) and p53."", can you determine the relation? downregulator Regarding ""Kynurenic acid (<< KA >>) is an endogenous glutamate receptor antagonist at the level of the different [[ ionotropic glutamate receptors ]]."", can you determine the relation? antagonist Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Pre-clinical pharmacology of zolmitriptan (<< Zomig >>; formerly 311C90), a centrally and peripherally acting [[ 5HT1B/1D ]] agonist for migraine."", can you determine the relation? agonist Regarding ""The << Na channel >> block caused by [[ lidocaine ]] and RSD1235 can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells."", can you determine the relation? inhibitor Regarding ""<< HSYA >> suppressed the expression of TLR-4, Myd88, [[ ICAM-1 ]], TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells."", can you determine the relation? indirect-downregulator Regarding ""The << COX >> pathway generates inflammatory [[ prostaglandins ]], while the 5-LOX pathway generates inflammatory leukotrienes."", can you determine the relation? product-of Regarding ""The M564G mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type << CrAT >>, and lower activity toward its natural substrate, [[ acetyl-CoA ]]."", can you determine the relation? substrate Regarding ""Treatment of A549 and H1299 cells with << dioscin >> caused a dose-dependent increase in ERK1/2 and [[ JNK1/2 ]] activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR."", can you determine the relation? upregulator Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""Furthermore, << galangin >> attenuated [[ IgE ]]-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 463,"Consider the text ""8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by [[ tolbutamide ]] was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor bisindolylmaleimide I (1 μM)."". Can you identify the relation? indirect-upregulator Consider the text ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""Pharmacologically, << troglitazone >> is a novel inhibitor of [[ ENT1 ]]."". Can you identify the relation? inhibitor Consider the text ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."". Can you identify the relation? substrate_product-of Consider the text ""Synthesis and antagonistic activity at << muscarinic receptor >> subtypes of some [[ 2-carbonyl ]] derivatives of diphenidol."". Can you identify the relation? antagonist Consider the text ""<< HSYA >> treatment also decreased [[ NF-κB ]] p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK)."". Can you identify the relation? downregulator Consider the text ""The experiments were performed on 80 male Wistar rats, 58 of which survived, subdivided into 3 groups: C-control rats, I-EAP group, and II-EAP group treated with the << adenosine A3 receptor >> agonist [[ IB-MECA ]] (1-deoxy-1-6[[(3-iodophenyl) methyl]amino]-9H-purin-9-yl)-N-methyl-B-D-ribofuronamide at a dose of 0.75 mg/kg b.w."". Can you identify the relation? agonist Consider the text ""The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of [[ caspase-9 ]] and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways."". Can you identify the relation? activator Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""In addition, we found that << neoechinulin A >> significantly suppressed the production of neurotoxic inflammatory mediator [[ tumour necrosis factor-α ]] (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells."". Can you identify the relation? indirect-downregulator Consider the text ""Beta-1,4-galactosyltransferase I (beta4Gal-T1) normally transfers Gal from << UDP-Gal >> to GlcNAc in the presence of Mn(2+) ion ([[ Gal-T ]] activity) and also transfers Glc from UDP-Glc to GlcNAc (Glc-T activity), albeit at only 0.3% efficiency."". Can you identify the relation? substrate Consider the text ""<< CYP1A1 >> and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures (approximately 5% of [[ TCDD ]] potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme."". Can you identify the relation? upregulator Consider the text ""The primary aim of these studies was to test the hypothesis that << HSD11B1 >>-derived [[ cortisol ]] has a biological role in endometrial function and conceptus development during early pregnancy in sheep."". Can you identify the relation? product-of Consider the text ""Thus we have shown that low-dose << theophylline >> exerts an anti-asthma effect through increasing activation of [[ HDAC ]] which is subsequently recruited by corticosteroids to suppress inflammatory genes."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 464,"In reference to ""<< Cholesterol esterase >> (CE) induced surface erosion of [[ poly(ethylene carbonate) ]] (PEC) and drug release from PEC under mild physiological environment was investigated."", what is the relation? substrate In reference to ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (<< 1O2 >>) donor chloramine T (CT), to destroy [[ plasmatic PAI-1 ]] and alpha2-antiplasmin."", what is the relation? downregulator In reference to ""The beta-adrenergic/<< 5-HT1A >> receptor antagonist [[ (+/-)pindolol ]] and the selective 5-HT1B/D antagonist GR127935 produced no significant augmentation of venlafaxine-induced changes in either 5-HT or NA."", what is the relation? antagonist In reference to ""In vitro studies with blood-derived T cells, however, show inhibition of all three << cytokines >> by [[ GCS ]]."", what is the relation? inhibitor In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of In reference to ""It is concluded that << D-1997 >> contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the [[ 5-HT1A ]] or 5-HT1B receptor subtypes."", what is the relation? activator In reference to ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma."", what is the relation? agonist-activator In reference to ""Furthermore, tPA induced rapid << tyrosine >> phosphorylation on the beta subunit of LRP-1, which was followed by the activation of Mek1 and its downstream [[ Erk-1 and -2 ]]."", what is the relation? indirect-upregulator In reference to ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/[[ CIP1 ]]) and p53."", what is the relation? upregulator In reference to ""Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [[[ 9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol ]]], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia."", what is the relation? agonist In reference to ""Furthermore, N-<< BPs >> decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and [[ mTOR ]] via suppression of Ras prenylation and enhanced Bim expression."", what is the relation? indirect-downregulator In reference to ""Favorable enzyme profiles (high << TP >> and low DPD) generate high intratumor levels of [[ 5-FU ]] that are effective against many tumors, especially those with low TS."", what is the relation? product-of In reference to ""In agreement with these data, the exogenous treatment of << SAH >> or inhibition of SAHH by specific siRNA or another type of inhibitor, 3-deazaadenosine (DAZA), similarly resulted in antitumorigenic responses, suppressive activity on [[ Src ]], the alteration of actin cytoskeleton, and a change of the colocalization pattern between actin and Src."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 465,"Consider the text ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and [[ p53 ]]."". Can you identify the relation? upregulator Consider the text ""The esterified-<< BM >>, however, had only partial transactivation agonistic activity in cells transfected with [[ rat GR ]], whereas BM and esterified-DEX had full transactivation agonistic activity."". Can you identify the relation? agonist Consider the text ""Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing NF-κB activity and induction of [[ Nrf2 ]]-dependent HO-1 activity."". Can you identify the relation? downregulator Consider the text ""Intravenous << arginine >> significantly increased the acute [[ glucagon ]] response (129 +/- 12 vs 36 +/- 6 ng/l in controls; p < 0.01), notably without affecting plasma glucose."". Can you identify the relation? indirect-upregulator Consider the text ""METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (<< SB-207266 >>) on the cisapride mediated increase in plasma aldosterone (a [[ 5-HT(4) ]] mediated response) and orocaecal transit in 18 subjects."". Can you identify the relation? antagonist Consider the text ""Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and << midazolam >> (MDZ) as an inducer and a substrate to [[ CYP3A ]], respectively."". Can you identify the relation? activator Consider the text ""At PND35, the medial prefrontal cortex (mPFC) of rats given << MPH >> showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter ([[ NET ]])-ir density."". Can you identify the relation? indirect-downregulator Consider the text ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."". Can you identify the relation? agonist-inhibitor Consider the text ""Block of << human NaV1.5 >> [[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin."". Can you identify the relation? substrate Consider the text ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."". Can you identify the relation? agonist-activator Consider the text ""CONCLUSIONS: Our results show that << indomethacin >>, a known cyclooxygenase ([[ COX ]]) inhibitor, is also an activator of CA."". Can you identify the relation? inhibitor Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""To begin to examine whether these changes are mediated by alterations in gene expression for << tryptophan hydroxylase >> (TPH), the rate-limiting enzyme in [[ 5-HT ]] biosynthesis, we quantitated its mRNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR)."". Can you identify the relation? product-of Consider the text ""We developed a computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC) behaviors for endocrine effects of the << aromatase >> inhibitor, [[ fadrozole ]] (FAD)."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 466,"Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner. Question: what is the relation? Answer: upregulator Systemic administration of << beta2-adrenoceptor >> agonists, formoterol and [[ salmeterol ]], elicit skeletal muscle hypertrophy in rats at micromolar doses. Question: what is the relation? Answer: agonist One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of Comparison of all the << beta-adrenoceptor >> antagonists tested revealed a potency order of [[ propranolol ]]>betaxolol approximately levobetaxolol>levobunolol approximately carteolol>/=timolol>atenolol. Question: what is the relation? Answer: antagonist Functional and biochemical studies indicated that << TES >> signaling involved activity of the phosphoinositide 3 (PI3) kinase-protein kinase B (Akt) cascade initiated by activation of the [[ androgen receptor ]] and culminated in enhanced production of cGMP and microvascular vasodilation. Question: what is the relation? Answer: activator In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. Question: what is the relation? Answer: agonist-activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. Question: what is the relation? Answer: agonist-inhibitor The results showed that IR tyrosine phosphorylation (pIR) was reduced by 42 % in MSG-obese mice (<< MSG >>, 6.7 ± 0.2 arbitrary units (a.u.); control, 11.5 ± 0.4 a.u.); on the other hand, exercise training increased [[ pIR ]] by 76 % in MSG mice without affecting control mice (MSG, 11.8 ± 0.3; control, 12.8 ± 0.2 a.u.). Question: what is the relation? Answer: downregulator In addition, the number and area of glutathione S-transferase placental form (GST-P) positive foci and << proliferating cell nuclear antigen >> (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg [[ MEG ]] compared with the control animals. Question: what is the relation? Answer: indirect-upregulator During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and << cortisol >> via [[ hydroxysteroid (11-β) dehydrogenase 1 ]] (HSD11B1). Question: what is the relation? Answer: product-of The M564G mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type << CrAT >>, and lower activity toward its natural substrate, [[ acetyl-CoA ]]. Question: what is the relation? Answer: substrate These protective effects were abolished by glucocorticoid receptor (GR) antagonist RU486 or << p-ERK >> inhibitor [[ U0126 ]] rather than estrogen receptor α antagonist ICI 82,780. Question: what is the relation? Answer: inhibitor Furthermore, << sinapic acid >> reduced hepatic hydroxyproline content, which correlated with a reduction in the expression of [[ type I collagen ]] mRNA and histological analysis of collagen in liver tissue. Question: what is the relation? Answer: indirect-downregulator Herein, we evaluate the interaction of the << alpha(2)-AR antagonist >>, [[ yohimbine ]], as compared to fluparoxan, at multiple monoaminergic receptors and examine their roles in the modulation of adrenergic, dopaminergic and serotonergic transmission in freely-moving rats. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 467,"In reference to ""N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide (<< NS-398 >>), a selective [[ cyclooxygenase-2 ]] inhibitor, also inhibited cell proliferation, whereas it did not cause apoptosis."", what is the relation? inhibitor In reference to ""RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]."", what is the relation? agonist-activator In reference to ""Direct-acting << CB1 >> agonists, including Δ(9)-tetrahydrocannabinol, [[ WIN 55,212 ]] [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia."", what is the relation? agonist In reference to ""However, Ca(2+) blockers also obviously attenuated << NF-κB >> activation and transnuclear transport induced by [[ TCDD ]]."", what is the relation? activator In reference to ""Subsequently, << pinosylvin >> suppressed the nuclear translocation of β-catenin, one of downstream molecules of PI3K/Akt/[[ GSK-3β ]] signaling, and these events led to the sequential downregulation of β-catenin-mediated transcription of target genes including BMP4, ID2, survivin, cyclin D1, MMP7, and c-Myc."", what is the relation? indirect-downregulator In reference to ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""<< EP(1) >> and EP(3) receptor antagonists ONO-8713 and [[ ONO-AE3-240 ]], but not the EP(4) antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP(1) and EP(3) but not EP(4) for MB growth."", what is the relation? antagonist In reference to ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats."", what is the relation? upregulator In reference to ""<< Mammalian ALDH1B1 >>, another mitochondrial enzyme sharing 72% identity with ALDH2, is also capable of metabolizing [[ acetaldehyde ]] but has a tissue distribution and pattern of activity distinct from that of ALDH2."", what is the relation? substrate In reference to ""Furthermore, treatment with spironoclactone not only attenuated the pro-apoptotic effect of ALD but reversed the << ALD >>-induced increase of [[ calpain ]] and AIF levels."", what is the relation? indirect-upregulator In reference to ""Moreover, << BH(4) >> treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, [[ nuclear factor-kappaB ]] and activating protein-1, which were increased in fructose-fed rats."", what is the relation? downregulator In reference to ""In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of AMP to << adenosine >> by [[ ecto-5'-nucleotidase ]]."", what is the relation? product-of In reference to ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""The Bcl2/Bax ratio increased and << Mfn2 >> expression decreased in MIN6 cells after [[ glucose ]] stimulation."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 468,"Consider the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA."". Can you identify the relation? substrate_product-of Consider the text ""PURPOSE: The << fluoropyrimidine carbamate >> (capecitabine) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase ([[ TP ]]) inside target tissues."". Can you identify the relation? substrate Consider the text ""<< HSYA >> suppressed the expression of TLR-4, Myd88, ICAM-1, TNFα, IL-1β and [[ IL-6 ]] at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells."". Can you identify the relation? indirect-downregulator Consider the text ""<< Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line."". Can you identify the relation? upregulator Consider the text ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity."". Can you identify the relation? agonist-activator Consider the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."". Can you identify the relation? agonist-inhibitor Consider the text ""Selective antagonism of GluR5 << kainate-receptor >>-mediated synaptic currents by [[ topiramate ]] in rat basolateral amygdala neurons."". Can you identify the relation? antagonist Consider the text ""Systemic administration of << beta2-adrenoceptor >> agonists, formoterol and [[ salmeterol ]], elicit skeletal muscle hypertrophy in rats at micromolar doses."". Can you identify the relation? agonist Consider the text ""The refolding kinetics of guanidine-denatured disulfide-intact << bovine pancreatic ribonuclease A >> (RNase A) and its proline-42-to-alanine mutant (Pro42Ala) have been studied by monitoring tyrosine burial and [[ 2'-cytidine monophosphate ]] (2'CMP) inhibitor binding."". Can you identify the relation? inhibitor Consider the text ""<< Follicle-stimulating hormone >> (FSH), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex [[ steroids ]] and gametes."". Can you identify the relation? product-of Consider the text ""Taken together, these findings indicate that << antofine >> induces Cx43 gap junction disassembly by the [[ PKCβ ]] signaling pathway."". Can you identify the relation? activator Consider the text ""Low levels of << serotonin >> may reduce the density of the [[ serotonin transporter ]] (SERT) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response""."". Can you identify the relation? downregulator Consider the text ""<< I3A >> induced a higher level of secretion of the inflammatory [[ cytokine ]] interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction."". Can you identify the relation? indirect-upregulator Consider the text ""Based on the results from those studies, we concluded that << rasagiline >> PO QD, at the therapeutic dosage range of 0.5 to 1 rag/d, is effective and well tolerated and completely, selectively, and specifically inhibited [[ MAO-B ]]."". Can you identify the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 469,"In reference to ""We evaluated the effects of angiotensin II and an << angiotensin-converting enzyme >> inhibitor ([[ cilazapril ]]) on nerve blood flow (NBF) and electrophysiology in control and diabetic rats."", what is the relation? inhibitor In reference to ""Inhibition of p95ErbB2, p185ErbB2, and EGFR phosphorylation by << GW572016 >> resulted in the inhibition of downstream phospho-Erk1/2, phospho-[[ AKT ]], and cyclin D steady-state protein levels."", what is the relation? indirect-downregulator In reference to ""CYP1A1 and CYP1A2 mRNAs were also increased by << pelargonidin >> in three primary human hepatocytes cultures (approximately 5% of TCDD potency) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of [[ CYP1A1 ]] enzyme."", what is the relation? upregulator In reference to ""ZD1839 (""Iressa""), a << quinazoline tyrosine >>[[ tyrosine kinase ]] inhibitor selective for the EGFR, has shown good activity in preclinical studies and in the early phase of clinical trials."", what is the relation? substrate In reference to ""Differentiating the roles of mGlu2 and mGlu3 receptors using << LY541850 >>, an mGlu2 agonist/[[ mGlu3 ]] antagonist."", what is the relation? antagonist In reference to ""In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and [[ Bax ]] proteins."", what is the relation? indirect-upregulator In reference to ""<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate ([[ PMA ]]) in WEHI-231, HOP-92, and Colo-205 cells."", what is the relation? downregulator In reference to ""Cardiac effects of the << beta 3-adrenoceptor >> agonist [[ BRL35135 ]] in man."", what is the relation? agonist In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator In reference to ""The latter reaction, catalyzed by << aspartoacylase >> (ASPA), produces [[ acetyl ]] groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter."", what is the relation? product-of In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""The results reinforce previous assumptions that << dopamine >> may interact with eicosanoid metabolism by means of [[ D(2) receptor ]] activation, and implicate an involvement of cPLA(2) and COX-2 in this effect."", what is the relation? activator In reference to ""Rats intoxicated with << Cd >> for 30 days, significantly increased tissue malondialdehyde (MDA) levels and significantly decreased enzymatic antioxidants superoxide dismutase, [[ glutathione peroxidase ]] and catalase in the frontal cortex tissue."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",9,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",downregulator 470,"<< Epi >> increased the activity of the [[ human WNT6 promoter ]] through Cav1-dependent binding of β-catenin to the proximal WNT6 promoter. Question: what is the relation? Answer: activator Our results have shown that << MMP-9 >> messenger ribonucleic acid (mRNA) expression was inhibited by [[ doxycycline ]] starting at 10 mg/kg/day (P<0.02). Question: what is the relation? Answer: indirect-downregulator In the present study, we identified << amprenavir >>, a widely used HIV PI, as a potent [[ PXR ]]-selective agonist. Question: what is the relation? Answer: agonist Synergistic cytotoxicity was demonstrated, and << pemetrexed >> significantly decreased the amount of phosphorylated Akt, enhanced apoptosis, and increased the expression of dCK in A549 and Calu-6 cells, as well as the expression of the human nucleoside equilibrative transporter 1 ([[ hENT1 ]]) in all cell lines. Question: what is the relation? Answer: indirect-upregulator << [6]-Gingerol >> derived from Zingiber officinale Roscoe (ginger) was identified as a novel [[ angiotensin II type 1 receptor ]] antagonist, with an IC50 value of 8.173 µM. Question: what is the relation? Answer: antagonist Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Question: what is the relation? Answer: agonist-inhibitor << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. Question: what is the relation? Answer: agonist-activator << Leukotriene A(4) hydrolase >> (LTA(4)H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to [[ LTB(4) ]]. Question: what is the relation? Answer: product-of Mutation of arginine 228 to << lysine >> enhances the [[ glucosyltransferase ]] activity of bovine beta-1,4-galactosyltransferase I. Question: what is the relation? Answer: upregulator << N(5)-Substituted H(4)biopterin >> derivatives were not oxidized to products serving as substrates for [[ dihydropteridine reductase ]] and,depending on the substituent, were competitive inhibitors of phenylalanine hydroxylase: N(5)-methyl- and N(5)-hydroxymethyl H(4)biopterin inhibited phenylalanine hydroxylase, whereas N(5)-formyl- and N(5)-acetyl H(4)biopterin had no effect. Question: what is the relation? Answer: substrate It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of [[ I-κBε ]] and nuclear translocation of c-Rel/p50 in alveolar epithelial cells. Question: what is the relation? Answer: downregulator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Question: what is the relation? Answer: substrate_product-of When selectively applied to channels after inducing slow inactivation with a 60-s pulse to -10 mV, << mibefradil >> (1 microM) produced 45% fractional block in Nav1.5 and greater block (88%) in an isoform ([[ Nav1.4 ]]) that slow-inactivates more completely. Question: what is the relation? Answer: inhibitor Inactivation of prostaglandin H synthase and << prostacyclin synthase >> by [[ phenylbutazone ]]. Question: what is the relation? Answer: Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 471,"CONCLUSIONS: These results indicate that << etomidate >> acts as an agonist at [[ alpha2-adrenoceptors ]], which appears in vivo primarily as an alpha2B-receptor-mediated increase in blood pressure. what is the relation? agonist Furthermore, cAMP production and protein kinase A (<< PKA >>) activity were suppressed by [[ artemisinic acid ]]. what is the relation? inhibitor RESULTS: Pretreatment of lung tissues with << pranlukast >> alone significantly decreased the amount of [[ IL-5 ]] protein in the culture medium by 40%. what is the relation? indirect-downregulator The sympathetic nerves of both the human atrial appendages and rabbit pulmonary artery are endowed with << alpha(2A)-autoreceptors >>, at which, however, both [[ rilmenidine ]] and oxymetazoline exhibit different properties (antagonism and agonism, respectively). what is the relation? antagonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and << activating protein-1 >>, which were increased in [[ fructose ]]-fed rats. what is the relation? upregulator PGE(2) is synthesized from << arachidonic acid >> by cyclooxygenases (COX) and prostaglandin E synthases ([[ PGES ]]) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). what is the relation? substrate Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones [[ glucagon-like peptide-1 ]] and glucose-dependent insulinotropic polypeptide. what is the relation? indirect-upregulator << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), [[ CDK4 ]], c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53. what is the relation? downregulator To begin to examine whether these changes are mediated by alterations in gene expression for << tryptophan hydroxylase >> (TPH), the rate-limiting enzyme in [[ 5-HT ]] biosynthesis, we quantitated its mRNA levels by competitive reverse transcription-polymerase chain reaction (RT-PCR). what is the relation? product-of RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of PPARalpha and [[ PPARgamma ]]. what is the relation? agonist-activator In HEK-293 cells stably transfected with this receptor, << serotonin >> elicits a potent stimulation of [[ adenylyl cyclase ]] activity, which is blocked by antipsychotic and antidepressant drugs. what is the relation? activator One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). what is the relation? substrate_product-of CK significantly inhibited << DMN >>-induced increases in serum alanine aminotransferase ([[ ALT ]]) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",3,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",activator 472,"Regarding the sentence ""Low levels of << serotonin >> may reduce the density of the serotonin transporter ([[ SERT ]]) by either increasing trafficking or reducing synthesis; a ""neuroadaptive response""."", what is the relation? downregulator Regarding the sentence ""Furthermore, proteosomal inhibitor MG132 suppressed << AMPK >> activation, GSK3β phosphorylation, cleaved PARP and deceased AEG-1 induced by [[ ursolic acid ]] in HepG2 cells."", what is the relation? activator Regarding the sentence ""TAS-102 is a novel drug containing << trifluorothymidine >>, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS."", what is the relation? substrate Regarding the sentence ""<< Cycloxygenase-2 >> (COX-2)-derived [[ prostaglandin E2 ]] (PGE2) has been shown to be important in esophageal tumorigenesis."", what is the relation? product-of Regarding the sentence ""Compared with the untreated colitis group, the << curcumin >>-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-κB mRNA, [[ IL-27 ]] mRNA, TLR4 protein, NF-κB p65 protein, and IL-27 p28 protein (p < 0.05)."", what is the relation? indirect-downregulator Regarding the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", what is the relation? agonist-activator Regarding the sentence ""Tissue-type plasminogen activator (tPA), a << serine >> protease well known for generating [[ plasmin ]], has been demonstrated to induce matrix metalloproteinase-9 (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts."", what is the relation? indirect-upregulator Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of << diphenylhydantoin >> and examined their ability to inhibit human Na(V)1.5 [[ sodium channels ]] expressed in Chinese Hamster Ovary (CHO-K1) cells."", what is the relation? inhibitor Regarding the sentence ""Although generally highly specific for angiotensin II type 1 receptors, some ARBs, particularly << telmisartan >>, are partial agonists at [[ peroxisome proliferator-activated receptor-γ ]]."", what is the relation? agonist Regarding the sentence ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> (GTK, [[ EC 2.6.1.15 ]])."", what is the relation? substrate_product-of Regarding the sentence ""It is concluded that << labetalol >> and dilevalol are [[ beta 1-adrenoceptor ]] selective antagonists."", what is the relation? antagonist Regarding the sentence ""Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.)."", what is the relation? upregulator Regarding the sentence ""The mean body weight at baseline (52.59 kg) did not differ significantly from that at 1 week after treatment (52.84 kg; P > .05), but the mean << leptin >> level after 1 week of treatment with [[ cyproheptadine ]] (3.14 ng/mL) was 14.2% higher than that at baseline (2.75 ng/mL; P < .05)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 473,"Given the text ""To determine whether << 3,4-methylenedioxymethamphetamine >> (MDMA)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured."", describe the relation. downregulator Given the text ""Extracellular application of << meclofenamate >> (EC(50) = 25 microM) and diclofenac (EC(50) = 2.6 microM) resulted in the activation of [[ KCNQ2/Q3 ]] K(+) currents, heterologously expressed in Chinese hamster ovary cells."", describe the relation. activator Given the text ""Consumption of << alcohol >> for 8weeks induced severe liver damage with increases in prognostic indicators such as [[ aspartate transaminase ]], alanine transaminase in serum whereas co-administration of CNF suppressed their increases."", describe the relation. indirect-upregulator Given the text ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA."", describe the relation. substrate_product-of Given the text ""The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure."", describe the relation. agonist Given the text ""The potent and selective third-generation << aromatase >> inhibitors anastrozole, [[ letrozole ]] and exemestane were introduced to the market as endocrine therapy in postmenopausal patients failing anti-estrogen therapy alone, or multiple hormonal therapies."", describe the relation. inhibitor Given the text ""Saturated << palmitic and stearic acids >> increased ceramides, up-regulated [[ PTP1B ]], and had AKt and PTP1B phosphorylation at Ser 50 impaired."", describe the relation. upregulator Given the text ""We concluded that FDH has no direct role in the regulation of the above two pathways of Ser synthesis; the breakdown of formate to << CO(2) >> by the [[ FDH ]] reaction is the primary and preferred fate of the organic acid in Arabidopsis."", describe the relation. product-of Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""BACKGROUND: << Pranlukast >>, a [[ cysteinyl leukotriene receptor 1 ]] (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation."", describe the relation. antagonist Given the text ""They all expressed ASS, but not << ornithine transcarbamylase >> (OTC), the enzyme that converts [[ ornithine ]], the product of degradation of arginine with rhArg, to citrulline, which is converted back to arginine via ASS."", describe the relation. substrate Given the text ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", describe the relation. agonist-inhibitor Given the text ""Platelet-induced COX-2-dependent PGE2 synthesis in HT29 cells was involved in downregulation of p21(WAF1/CIP1) and upregulation of << cyclinB1 >>, since these effects were prevented by [[ rofecoxib ]](a selective COX-2 inhibitor) and rescued by exogenous PGE2."", describe the relation. indirect-downregulator Given the text ""Further study showed that << icariin >> dose-dependently inhibited the proliferation and activation of T lymphocytes, and suppressed pro-inflammatory [[ cytokine ]] levels of activated T cells."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 474,"Evidence has accumulated in the last few years that the expression of the << microsomal/peroxidase antigen >> (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis. what is the relation? upregulator << PGE(2) >> is synthesized from arachidonic acid by cyclooxygenases (COX) and prostaglandin E synthases ([[ PGES ]]) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). what is the relation? product-of In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. what is the relation? agonist-activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. what is the relation? substrate_product-of In the present study, we identified << amprenavir >>, a widely used HIV PI, as a potent [[ PXR ]]-selective agonist. what is the relation? agonist In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor Thus, << U50,488H >>-induced internalization and down-regulation of the [[ hkor ]] share initial common mechanisms. what is the relation? downregulator Recombinant << PDE10A >> transfected and expressed in COS-7 cells hydrolyzed cAMP and cGMP with Km values of 0.26 and 7.2 microM, respectively, and Vmax with cGMP was almost twice that with [[ cAMP ]]. what is the relation? substrate << Sulindac sulfide >> inhibited [[ PPARdelta ]] protein expression and PPARdelta transcriptional activity. what is the relation? indirect-downregulator The in vitro kinase activity of << PKC-alpha >> induced by I3A was lower than that induced by [[ PMA ]]. what is the relation? activator In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the << CB2 >> antagonist AM630 [[[ (6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone) ]]]. what is the relation? antagonist These findings demonstrate that cinnamon << polyphenols >> can exert the hypoglycemic and hypolipidemic effects through the mechanisms that may be associated with repairing pancreatic beta cells in diabetic mice and improving its anti-oxidative capacity, as well as attenuating cytotoxicity via inhibition of [[ iNOS ]], NF-κB activation. what is the relation? inhibitor Re-feeding normal chow or a high << sucrose >> diet for 24 h after a 48-h fast increased both [[ ACS1 ]] and ACS4 protein expression 1.5-2.0-fold, consistent with inhibition studies. what is the relation? indirect-upregulator Cyclooxygenase-1 (COX-1) inhibitors (flurbiprofen, ketoprofen and ketrolack) attenuated the nicotine-induced contraction in a concentration-dependent manner, and << cyclooxygenase-2 >> (COX-2) inhibitors at high concentrations (nimesulide and [[ NS-389 ]]) slightly attenuated the contraction. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 475,"Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and << NOX4 >>, which were prevented by [[ resveratrol ]]. what is the relation? downregulator With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) << PhIP >> at the doses of 10mg/kg and/or 15mg/kg significantly inhibited [[ p16 ]] mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control. what is the relation? indirect-downregulator << Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol. what is the relation? agonist-activator Thus, << SFO >> contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and [[ IL-8 ]] and cell apoptosis in plaque. what is the relation? activator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. what is the relation? substrate_product-of In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor Furthermore, proteosomal inhibitor << MG132 >> suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased [[ AEG-1 ]] induced by ursolic acid in HepG2 cells. what is the relation? indirect-upregulator The beta subunit has been cloned and shown to lower the K(m) of << methionine adenosyltransferase II alpha2 >> (the MAT2A product) for [[ methionine ]] and to render the enzyme more susceptible to S-adenosylmethionine inhibition. what is the relation? substrate It is concluded that << labetalol >> and dilevalol are [[ beta 1-adrenoceptor ]] selective antagonists. what is the relation? antagonist << Amitriptyline >> is a TrkA and [[ TrkB ]] receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. what is the relation? agonist << Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line. what is the relation? upregulator Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of << NO >> and the expression of [[ inducible nitric-oxide synthase ]] (iNOS) in human U373MG astroglial cells and primary astrocytes. what is the relation? product-of The acetylcholinesterase (AChE) and butyrylcholinesterase (<< BuChE >>) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ [[ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine ]] (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described. what is the relation? inhibitor Analysis of natural genetic variation among inbred strains of mice indicates that << FMO3 >> and [[ TMAO ]] are significantly correlated, and TMAO levels explain 11% of the variation in atherosclerosis. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",0,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",product-of 476,"Carnitine acetyltransferases (<< CrAT >>) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Please explain the relation. substrate New classes of pyrrole-derived << nitrooxyalkyl >> inverse esters, carbonates, and ethers (7-10) as [[ COX-2 ]] selective inhibitors and NO donors were synthesized and are herein reported. Please explain the relation. inhibitor << Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, cyclin A, cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein ([[ pRb ]]), and the upregulation of p21(WAF1/CIP1) and p53. Please explain the relation. downregulator << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA. Please explain the relation. substrate_product-of In whole-cell voltage-clamp recordings from principal neurons of the rat basolateral amygdala, << topiramate >> at low concentrations (IC50, approximately 0.5 microm) selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by kainate receptors containing the [[ GluR5 ]] subunit. Please explain the relation. indirect-downregulator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Results: The administration of << prallethrin >> 1.6% w/w created significant increased changes in the levels of total WBC, lymphocytes, RBC, hemoglobin, packed cell volume, platelets, mean corpuscular volume, and mean corpuscular [[ hemoglobin ]] in rats after 24, 48, and 72 h of continuous inhalation; however, there was a significant reduction in neutrophils at transient reduction in the monocytes after 24 and 48 h to return to normal after 72 h. Please explain the relation. indirect-upregulator The latter reaction, catalyzed by aspartoacylase (<< ASPA >>), produces acetyl groups plus [[ aspartate ]] and has been proposed to occur in both soluble and membranous subfractions of white matter. Please explain the relation. product-of Kynurenic acid (<< KA >>) is an endogenous glutamate receptor antagonist at the level of the different [[ ionotropic glutamate receptors ]]. Please explain the relation. antagonist Effect of (S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno-[5,4-b]furan-8-yl)ethyl]propionamide (ramelteon, << TAK-375 >>), a selective [[ MT1/MT2 receptor ]] agonist, on motor coordination was studied using rota-rod performance in mice. Please explain the relation. agonist CONCLUSION: A long-term intake of ethanol solution down-regulates the phosphorylation of << CREB >> in the nucleus accumbens, and those changes can be reversed by [[ naloxone ]], which may be one kind of the molecular mechanisms associated with ethanol dependence. Please explain the relation. upregulator RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Please explain the relation. agonist-activator Little is known in terms of multi-matrix << cytochrome P450 >> activity induction under repeated oral exposure to planar halogenated and polycyclic aromatic hydrocarbons (PHH, [[ PAH ]]). Please explain the relation. activator METHODS: After 1 month of HFD alone, the mice were given the << DPP4 >> inhibitor [[ vildagliptin ]] for a further 11 months. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 477,"Regarding ""Thus, the << TCDD >>-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and [[ Rspo3 ]]) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway."", can you determine the relation? downregulator Regarding ""We found that << PSE >> inhibits interleukin-2 (IL-2) and [[ tumor necrosis factor (TNF) alpha ]]-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line."", can you determine the relation? indirect-upregulator Regarding ""L-serine dehydratase (<< SDH >>), a member of the beta-family of pyridoxal phosphate-dependent (PLP) enzymes, catalyzes the deamination of L-serine and L-threonine to yield pyruvate or [[ 2-oxobutyrate ]]."", can you determine the relation? product-of Regarding ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", can you determine the relation? agonist-activator Regarding ""The << alpha(1)-adrenoceptor >> antagonist, [[ tamsulosin ]], is selective for alpha(1A)- and alpha(1D)- over alpha(1B)-adrenoceptors."", can you determine the relation? antagonist Regarding ""Little is known in terms of multi-matrix << cytochrome P450 >> activity induction under repeated oral exposure to planar halogenated and polycyclic aromatic hydrocarbons (PHH, [[ PAH ]])."", can you determine the relation? activator Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""<< Zolmitriptan >> (Zomig; formerly 311C90) is a novel [[ 5-hydroxytryptamine (5HT)1B/1D ]] receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura."", can you determine the relation? agonist Regarding ""The << calcium >> homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, phospholamban ([[ PLB ]]), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation."", can you determine the relation? substrate Regarding ""Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the << N >>-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent [[ PDE3 ]] inhibition."", can you determine the relation? inhibitor Regarding ""<< Minocycline >> treatment prevents the formation of activated [[ caspase-3 ]], a known effector of apoptosis, as well as the appearance of a calpain cleaved substrate, a marker of excitotoxic/necrotic cell death."", can you determine the relation? indirect-downregulator Regarding ""Evidence has accumulated in the last few years that the expression of the << microsomal/peroxidase antigen >> (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular [[ cAMP ]] accumulation and protein synthesis."", can you determine the relation? upregulator Regarding ""<< Thalidomide >> initiates its teratogenic effects by binding to CRBN and inhibiting the associated [[ ubiquitin ligase ]] activity."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 478,"Given the text ""Activation of << alpha 2B-adrenoceptors >> mediates the cardiovascular effects of [[ etomidate ]]."", describe the relation. activator Given the text ""Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the << beta(2)-adrenoceptor >> agonist [[ formoterol ]] [eformoterol]."", describe the relation. agonist Given the text ""Expression of the dominant negative mutants arrestin-2(319-418) or dynamin I-K44A significantly reduced << U50,488H >>-induced down-regulation of the [[ hkor ]]."", describe the relation. downregulator Given the text ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", describe the relation. agonist-inhibitor Given the text ""Similarly, pelargonidin induced the expression of << CYP1A1 >> mRNA up to 5-fold in HepG2 and LS174T cells relative to the induction by 5 nM 2,3,7,8-tetrachlorodibenzodioxin ([[ TCDD ]]), the most potent activator of AhR."", describe the relation. upregulator Given the text ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons."", describe the relation. agonist-activator Given the text ""We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (<< PhIP >>; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and [[ cyt b5 ]]."", describe the relation. substrate Given the text ""The << cytosine >> analog 5-aza-2'-deoxycytidine (decitabine) hypomethylates DNA by inhibiting [[ DNA methyltransferase ]]."", describe the relation. inhibitor Given the text ""After inflammation was established mice were dosed with the << H4R >> antagonist, [[ JNJ 7777120 ]], or anti-IL-13 antibody for comparison."", describe the relation. antagonist Given the text ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", describe the relation. substrate_product-of Given the text ""<< Swertiamarin >> treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-γ and GLUT-4; however, there was a significant increase in the mRNA expression of [[ adiponectin ]]."", describe the relation. indirect-upregulator Given the text ""Our results indicate that Salix extract 1520L inhibits << COX-2 >>-mediated [[ PGE2 ]] release through compounds other than salicin or salicylate."", describe the relation. product-of Given the text ""As revealed by glucose oxidase (GOD) and radioimmunoassay (RIA), both << dimethyldiguanide >> (DC, 0.6gkg(-1)d(-1)) and CPS (0.3, 0.6, 1.2gkg(-1)d(-1)) treatments significantly resulted in down-regulation of blood glucose and [[ insulin ]] levels in serum, while the levels of oxidative stress markers were markedly lowered through ELISA assay."", describe the relation. indirect-downregulator Given the text ""Sorafenib and << sunitinib >> are synthetic, orally active agents shown to directly inhibit vascular endothelial growth factor receptors -2 and -3 (VEGFR-2, VEGFR-3) and platelet-derived growth factor receptor beta ([[ PDGFR-beta ]]), while temsirolimus is an mTOR inhibitor."", describe the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 479,"Co-treatment of astrocytes with << antofine >> and the intracellular Ca(2+) chelator BAPTA-AM prevented downregulation of [[ Cx43 ]] and inhibition of GJIC. Query: What is the relation? indirect-downregulator In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of << ethylmorphine-N-demethylase >> and aniline 4-hydroxylase activity and cytochrome P450, compared to the [[ CCl4 ]] only group. Query: What is the relation? activator First, addition of << apolipoprotein A-I >> (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (ABCA1)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner. Query: What is the relation? product-of We previously reported that << aminoglycoside >> antibiotics reduce [[ SGLT1 ]]-dependent glucose transport in pig proximal tubular epithelial LLC-PK1 cells in parallel with the order of their nephrotoxicity. Query: What is the relation? downregulator In addition, inhibiting the binding of the fast inactivation lid (<< Nav1.5 >> ICM + MTSET) did not alter [[ mibefradil ]] block, confirming that the drug does not preferentially interact with the fast-inactivated state. Query: What is the relation? inhibitor Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers << DEX >> inhibited IL-2 production partially and enhanced [[ IL-2R alpha ]] expression and proliferation. Query: What is the relation? indirect-upregulator << Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Query: What is the relation? substrate_product-of << CPT I >> (carnitine palmitoyltransferase I) catalyses the conversion of [[ palmitoyl-CoA ]] into palmitoylcarnitine in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria. Query: What is the relation? substrate To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective << 5-HT1F >> receptor agonist ([[ LY 344864 ]]) on c-fos protein expression in the trigeminal nucleus caudalis. Query: What is the relation? agonist RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. Query: What is the relation? agonist-activator Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with << Nrf2 >> siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. Query: What is the relation? upregulator In order to examine the site of action of an NR2B subtype-selective << NMDA >> antagonist [[ CP-101,606 ]], we investigated its analgesic effect in a rat model of neuropathic pain at various routes of administration. Query: What is the relation? antagonist Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor The << (R)-omeprazole >> hydroxylation index reflects [[ CYP2C19 ]] activity in healthy Japanese volunteers. Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",5,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",substrate 480,"Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Query: What is the relation? agonist-inhibitor << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Query: What is the relation? substrate_product-of Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal [[ DA ]] transport. Query: What is the relation? substrate A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, << syringic acid >>, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, [[ EC 4.2.1.1 ]]). Query: What is the relation? inhibitor Moreover, LTD4-induced increases in CysLT(1)R and << NF-κB >> p65 in the brain were also attenuated by [[ pranlukast ]]. Query: What is the relation? indirect-downregulator Taken together, our findings indicate that 5HHMF suppresses << NO >> production through modulation of iNOS, consequently suppressing [[ NF-κB ]] activity and induction of Nrf2-dependent HO-1 activity. Query: What is the relation? downregulator RESULTS: In drug discrimination studies, lisuride fully mimicked the << 5-HT(1A) >> agonist [[ LY 293284 ]], only partially substituted for LSD and DOI, and failed to substitute for (+)-amphetamine. Query: What is the relation? agonist Based on these studies, the frequency of spontaneous tail contractions at 26 hpf - a developmental stage with minimal << AChE >> expression and activity - was significantly higher following exposure to [[ paraoxon ]] concentrations as low as 31.2 nM. Query: What is the relation? activator (+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and << RS 17053 >> appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned [[ human alpha 1D adrenoceptors ]]. Query: What is the relation? antagonist << DEX >> enhanced the ratio IFN-gamma/[[ IL-4 ]] (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). Query: What is the relation? upregulator The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Query: What is the relation? agonist-activator << PGE(2) >> is synthesized from arachidonic acid by [[ cyclooxygenases ]] (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). Query: What is the relation? product-of The values of mean corpuscular hemoglobin concentration and mean corpuscular << hemoglobin >> increased in the [[ STX ]] group. Query: What is the relation? indirect-upregulator Most drugs currently employed in the treatment of type 2 diabetes either target the sulfonylurea receptor stimulating << insulin >> release (sulfonylureas, [[ glinides ]]), or target the peroxisome proliferator-activated receptor (PPARgamma) improving insulin resistance (thiazolidinediones). Query: What is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 481,"One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15). Please explain the relation. substrate_product-of Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of << cytochrome c >> to the cytosol induced by [[ DZN ]]. Please explain the relation. indirect-upregulator A << naloxone-steroid hybrid azine >> with selective and long-acting opioid antagonism at [[ delta receptors ]] in vitro. Please explain the relation. antagonist << Sulindac sulfide >> inhibits [[ epidermal growth factor ]]-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells. Please explain the relation. inhibitor Pharmacology of << ramelteon >>, a selective MT1/[[ MT2 ]] receptor agonist: a novel therapeutic drug for sleep disorders. Please explain the relation. agonist << Estrogens >> are biosynthesised from androgens by the [[ CYP450 ]] enzyme complex called aromatase. Please explain the relation. product-of Activation of AMP-activated Protein Kinase and Phosphorylation of << Glycogen Synthase Kinase3 β >> Mediate [[ Ursolic Acid ]] Induced Apoptosis in HepG2 Liver Cancer Cells. Please explain the relation. activator Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased [[ superoxide dismutase ]] (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. Please explain the relation. downregulator Uptake of the radiolabeled model substrates << estradiol 17β-glucuronide >>, estrone 3-sulfate, and dehydroepiandrosterone sulfate (DHEAS) was determined in the absence and presence of compounds 1-6 using Chinese hamster ovary (CHO) cells stably expressing either OATP1B1 or [[ OATP1B3 ]]. Please explain the relation. substrate Additionally, << MPTP >> significantly down-regulated [[ Bcl-2 ]] expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in Bax expression, cytochrome C translocation to the cytosol, andcleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment. Please explain the relation. indirect-downregulator In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons. Please explain the relation. agonist-activator << Ribonucleotide reductase >> activity was found to be strongly increased in the [[ gemcitabine ]]-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line. Please explain the relation. upregulator The observed inhibition on IFN-gamma, GM-CSF, and IL-3 mRNA was blocked by the selective << beta2AR >> antagonist [[ ICI 118,551 ]] (10(-6) M) and by timolol (10(-6) M), a nonselective antagonist. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 482,"Question: What is the relation in the sentence ""Differences in magnitude of Na(+)-dependent << l-alanine >> uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells.""? upregulator Question: What is the relation in the sentence ""<< Loperamide >> is a peripheral opiate agonist able to inhibit [[ ACTH ]] secretion.""? indirect-downregulator Question: What is the relation in the sentence ""Because clinical studies investigating interactions between garlic and << human immunodeficiency virus protease >> inhibitors saquinavir and [[ ritonavir ]] have already been performed, we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first-pass intestinal metabolism changes.""? inhibitor Question: What is the relation in the sentence ""We confirm the correlation between higher << hCTR1 >> levels and higher [[ Pt ]]-drug uptake in tumor cells sensitive to the drug.""? substrate Question: What is the relation in the sentence ""In the hippocampus, << brexpiprazole >> acted as a full agonist at [[ 5-HT1A ]] receptors on pyramidal neurons.""? agonist-activator Question: What is the relation in the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.""? agonist-inhibitor Question: What is the relation in the sentence ""Moreover, << IGFBP-rP2 >> noticeably increased in response to TGF-beta1 and [[ all-trans retinoic acid ]] (atRA) in HPEC and PC-3 cells, and it decreased in response to IGF-I in HPEC.""? indirect-upregulator Question: What is the relation in the sentence ""These results indicate that the positive inotropic effect, mediated via << (+/-)-tamsulosin >>- and oxymetazoline-sensitive subtype of [[ alpha 1-adrenoceptors ]], is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates.""? antagonist Question: What is the relation in the sentence ""<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.""? substrate_product-of Question: What is the relation in the sentence ""Suppression of Src/<< ERK >> and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells.""? downregulator Question: What is the relation in the sentence ""Thus, << SFO >> contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and [[ IL-8 ]] and cell apoptosis in plaque.""? activator Question: What is the relation in the sentence ""Adenosine and N(6)-cyclopentyl-adenosine (<< CPA >>, [[ A1R ]] agonist) constricted MVs but not MAs.""? agonist Question: What is the relation in the sentence ""CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of [[ HDC ]] gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity.""? product-of Question: What is the relation in the sentence ""Binding domains of the oxytocin receptor for the selective << oxytocin receptor >> antagonist barusiban in comparison to the agonists oxytocin and [[ carbetocin ]].""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",10,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist 483,"Question: What is the relation in the sentence ""Moreover, << curcumin >> alleviated [[ Sim2 ]] expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia.""? indirect-upregulator Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.""? agonist-activator Question: What is the relation in the sentence ""The pharmacology of NCX inhibitors has been studied extensively since the development of << KB-R7943 >>, a prototype benzyloxyphenyl [[ NCX ]] inhibitor, in 1996.""? inhibitor Question: What is the relation in the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate PPARα/β/γ, and Rhizoma Coptis contains potential natural agonists of << PPARs >> besides [[ berberine ]].""? agonist Question: What is the relation in the sentence ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]].""? agonist-inhibitor Question: What is the relation in the sentence ""<< 2-Deoxyglucose >> increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on [[ AMPK ]] consensus sites but did not change the amount of TSC1 bound to TSC2.""? activator Question: What is the relation in the sentence ""Brain tissue analyses revealed that neonatal << quinpirole >> treatment produced a significant decrease in hippocampal [[ NGF ]], BDNF and ChAT that was eliminated by olanzapine treatment.""? indirect-downregulator Question: What is the relation in the sentence ""Reductive detoxification of << arylhydroxylamine >> carcinogens by human NADH cytochrome b5 reductase and [[ cytochrome b5 ]].""? substrate Question: What is the relation in the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15).""? substrate_product-of Question: What is the relation in the sentence ""First, addition of apolipoprotein A-I (apoA-I), a direct acceptor of the ATP-binding cassette transporter A1 (<< ABCA1 >>)-secreted lipids, increased [[ alpha-tocopherol ]] secretion in a dose-dependent manner.""? product-of Question: What is the relation in the sentence ""The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the << 5-HT(2A) >>-receptor antagonist [[ ketanserin ]] was without effect.""? antagonist Question: What is the relation in the sentence ""RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than [[ COX-1 ]] (IC(50) = 0.210 microM).""? downregulator Question: What is the relation in the sentence ""To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance.""? upregulator Question: What is the relation in the sentence ""In the present study we tested whether << propranolol >>, a [[ β-receptor ]] antagonist commonly used as antihypertensive drug, could ameliorate the cognitive impairments and increases in AD-related markers shown by the senescence-accelerated mouse prone-8 (SAMP8).""? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 484,"Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< Ozone >> plus PM(2.5) exposure, however, induced [[ CRP ]], IL-6, CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way."", can you determine the relation? indirect-upregulator Regarding ""The non-selective adenosine receptor antagonist (caffeine), and the selective << adenosine A1 receptor >> antagonist ([[ DPCPX ]]), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice."", can you determine the relation? antagonist Regarding ""The recent development of << H1-receptor >> antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of [[ histamine ]] in this condition."", can you determine the relation? agonist Regarding ""BACKGROUND & AIMS: Of the 2 genes (MAT1A, << MAT2A >>) encoding methionine adenosyltransferase, the enzyme that synthesizes [[ S-adenosylmethionine ]], MAT1A, is expressed in liver, whereas MAT2A is expressed in extrahepatic tissues."", can you determine the relation? product-of Regarding ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", can you determine the relation? agonist-activator Regarding ""<< NaAsO(2) >> increased the mRNA levels of the light and medium subunits of neurofilament and decreased the mRNA levels of tau and [[ tubulin ]] in a dose-dependent manner; no significant effect was found in the mRNA levels of the heavy subunit of neurofilament, microtubule-associated protein 2, or actin."", can you determine the relation? indirect-downregulator Regarding ""<< Tomudex >> treatment resulted in the decrease in p27(kip1) expression, with an increase in cyclin E and cdk2 protein expression and [[ kinase ]] activities 24 h after a 2-h exposure."", can you determine the relation? activator Regarding ""Catecholamines (adrenaline, noradrenaline and << dopamine >>) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, [[ EC 1.14.16.1 ]])."", can you determine the relation? inhibitor Regarding ""<< DEX >> enhanced the ratio [[ IFN-gamma ]]/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005)."", can you determine the relation? upregulator Regarding ""A dose of 25 microg kg(-1) day(-1) of formoterol elicited greater EDL and soleus hypertrophy than << salmeterol >>, but resulted in similar [[ beta-adrenoceptor ]] downregulation."", can you determine the relation? downregulator Regarding ""<< Carboxylesterases >> hydrolyze esters, amides, and [[ thioesters ]] to produce carboxylic acids and resulting alcohols, amines, and thiols, respectively."", can you determine the relation? substrate Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Small molecules bearing hydroxamic acid as the << zinc >> binding group (ZBG) have been the most effective histone deacetylase inhibitors ([[ HDAC ]]i) to date."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 485,"Regarding the sentence ""To identify important covariates associated with interindividual variation in CYP2B6 activity in vivo, we evaluated these effects in healthy volunteers using bupropion (<< Wellbutrin SR >> GlaxoSmithKline, Research Triangle Park, NC) as a [[ CYP2B6 ]] probe substrate."", what is the relation? substrate Regarding the sentence ""OBJECTIVE: << Celecoxib >> and rofecoxib are two relatively new nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the cyclo-oxygenase-2 ([[ COX-2 ]]) isoenzyme at therapeutic concentrations."", what is the relation? inhibitor Regarding the sentence ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively."", what is the relation? upregulator Regarding the sentence ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of Regarding the sentence ""<< Acetylcholinesterase >> (AChE) inhibited by the organophosphate soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by [[ oximes ]] due to dealkylation of the soman-enzyme complex."", what is the relation? activator Regarding the sentence ""Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of << NO >> and the expression of inducible nitric-oxide synthase ([[ iNOS ]]) in human U373MG astroglial cells and primary astrocytes."", what is the relation? product-of Regarding the sentence ""Finally, the amounts of RORalpha and << cAspAT >> mRNAs were similarly increased by [[ TZD ]] treatment of human adipose tissue explants, confirming coordinated regulation."", what is the relation? indirect-upregulator Regarding the sentence ""The << A2A adenosine receptor >> agonist [[ CGS21680 ]] (C23H29N7O6.HCl.xH2O) (0.001-0.1 μM) did not alter NE oxidation currents."", what is the relation? agonist Regarding the sentence ""Considerable attention has focused on the investigation of theories to explain the better tolerability of << memantine >> over other [[ NMDA receptor ]] antagonists, particularly those that act by a similar channel blocking mechanism such as dissociative anesthetic-like agents (phencyclidine, ketamine, MK-801)."", what is the relation? antagonist Regarding the sentence ""RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than [[ COX-1 ]] (IC(50) = 0.210 microM)."", what is the relation? downregulator Regarding the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor Regarding the sentence ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator Regarding the sentence ""In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of << TCDD >> on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and [[ Wif1 ]], established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD."", what is the relation? indirect-downregulator Regarding the sentence ""Moreover, NO production in LPS-stimulated macrophages that are expressing CSE mRNA was significantly reduced by the addition of L-Cys, a substrate for H(2)S, but enhanced by the selective CSE inhibitor beta-cyano-L-alanine but not by the << CBS >> inhibitor [[ aminooxyacetic acid ]]."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 486,"Regarding the sentence ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", what is the relation? substrate_product-of Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction."", what is the relation? antagonist Regarding the sentence ""<< Rofecoxib >> only diminished COX-2 protein expression and [[ MCP-1 ]] gene expression in vascular atheroma."", what is the relation? indirect-downregulator Regarding the sentence ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."", what is the relation? upregulator Regarding the sentence ""Overall, our findings suggest that << ursolic acid >> induced apoptosis in HepG2 cells via [[ AMPK ]] activation and GSK3β phosphorylation as a potent chemopreventive agent."", what is the relation? activator Regarding the sentence ""The involvement of EP1 and EP2 receptors is indicated by studies with the << EP1 >> selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists [[ SC-51089 ]] (EP1 specific) and AH 6809 (EP1 and EP2 specific)."", what is the relation? agonist Regarding the sentence ""These results suggest that the altered << gamma-glutamyl kinase >> results in stabilization of the complex or has an indirect effect on gamma-glutamyl phosphate reductase activity, which leads to an increase in [[ L-proline ]] production in Saccharomyces cerevisiae."", what is the relation? product-of Regarding the sentence ""<< [-]-Huperzine A >> ([-]-Hup A), is a naturally occurring potent reversible [[ AChE ]] inhibitor that penetrates the blood-brain barrier."", what is the relation? inhibitor Regarding the sentence ""<< Phenylephrine >> elicited a concentration-dependent positive inotropic effect via [[ alpha 1-adrenoceptors ]] in the presence of either (+/-)-bupranolol or S(-)-timolol."", what is the relation? agonist-activator Regarding the sentence ""Furthermore, compared with control groups, the plaque endothelium level of p75(NTR) was 3-fold increased and the liver level of << p75(NTR) >> was 17.4-fold increased by [[ SFO ]]-HD."", what is the relation? indirect-upregulator Regarding the sentence ""<< Pinosylvin >> inhibited the proliferation of HCT 116 cells by arresting transition of cell cycle from G1 to S phase along with the downregulation of cyclin D1, cyclin E, [[ cyclin A ]], cyclin dependent kinase 2 (CDK2), CDK4, c-Myc, and retinoblastoma protein (pRb), and the upregulation of p21(WAF1/CIP1) and p53."", what is the relation? downregulator Regarding the sentence ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", what is the relation? agonist-inhibitor Regarding the sentence ""For determination of [PA+<< Pli >>]-activity, [[ arginine ]] was added after this incubation."", what is the relation? substrate Regarding the sentence ""Finally, << DMF >> suppressed unilateral ureteral obstruction (UUO)-induced renal fibrosis and alpha-SMA, fibronectin and type 1 collagen expression in the obstructed kidneys from UUO mice, along with increased and decreased expression of Nrf2 and [[ phospho-Smad3 ]], respectively."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 487,"Regarding ""Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2."", can you determine the relation? agonist-inhibitor Regarding ""The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""Luciferase reporter assays showed that transcription of << FDX1 >> was synergistically activated by the NR5A family and [[ 8Br-cAMP ]] treatment through two SF-1 binding sites and a CRE-like sequence in a human ovarian granulosa cell line, KGN."", can you determine the relation? indirect-upregulator Regarding ""Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect of an << NR2B >> subunit-selective antagonist [[ CP-101,606 ]] in a rat chronic constriction injury model."", can you determine the relation? antagonist Regarding ""Brexpiprazole reversed the inhibitory effect of the DA agonist << apomorphine >> on VTA DA neurons (ED50 = 61 mug/kg), whereas it was ineffective when administered alone, indicating partial agonistic action on [[ D2 receptors ]]."", can you determine the relation? agonist Regarding ""Since << gemfibrozil >> is known to activate [[ peroxisome proliferator-activated receptor-alpha ]] (PPAR-alpha), we investigated the role of PPAR-alpha in gemfibrozil-mediated inhibition of iNOS."", can you determine the relation? activator Regarding ""2.  We have developed a convenient quantitative multi-well plate assay to measure the glucuronidation rate of << 7-hydroxy-4-trifluoromethylcoumarin >> (HFC) for several [[ UGTs ]]."", can you determine the relation? substrate Regarding ""db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity and 651% and 77% increases in the beta-oxidation enzymes [[ carnitine palmitoyltransferase ]] and carnitine acetyltransferase, respectively."", can you determine the relation? upregulator Regarding ""BACKGROUND: << Rivastigmine >> is a carbamate drug designed to inhibit both [[ acetylcholinesterase ]] and butyrylcholinesterase by reversibly covalently bonding to these enzymes."", can you determine the relation? inhibitor Regarding ""Dexamethasone (<< DEX >>) inhibited the anti-CD3-induced production of [[ IL-4 ]], IL-5 and IFN-gamma in all 20 clones tested."", can you determine the relation? indirect-downregulator Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (KATI), also catalyses the reversible transamination of glutamine to << oxoglutaramic acid >> ([[ GTK ]], EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""<< N-Acetylglucosamine-1-phosphodiester alpha-N-Acetylglucosaminidase >> (EC 3.1.4.45; phosphodiester alpha-GlcNAcase) catalyzes the second step in the synthesis of the [[ mannose 6-phosphate ]] determinant required for efficient intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome."", can you determine the relation? product-of Regarding ""The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) << PhIP >> (10 and/or 15mg/kg) significantly decreased superoxide dismutase ([[ SOD ]]) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control."", can you determine the relation? downregulator Regarding ""<< Verrucarin A >> sensitizes TRAIL-induced apoptosis via the upregulation of DR5 in an [[ eIF2α ]]/CHOP-dependent manner."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 488,"<< Type 2 11β-hydroxysteroid dehydrogenase >> encoded by the HSD11B2 gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. what is the relation? agonist-activator When cultured in liquid minimal medium, yeast cells expressing the mutated << gamma-glutamyl kinase >> were found to accumulate intracellular [[ L-proline ]] and showed a prominent increase in cell viability after freezing at -20 degrees C compared to the viability of cells harboring the wild-type PRO1 gene. what is the relation? product-of Dexamethasone (<< DEX >>) inhibited the anti-CD3-induced production of IL-4, IL-5 and [[ IFN-gamma ]] in all 20 clones tested. what is the relation? indirect-downregulator Our data identify << cAspAT >> as a new member of glyceroneogenesis, transcriptionally regulated by [[ TZD ]] via the control of RORalpha expression by PPARgamma in adipocytes. what is the relation? indirect-upregulator OBJECTIVES: The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha2 adrenergic receptor (<< AR >>) agonist ([[ dexmedetomidine ]]). what is the relation? agonist The most potent compound, << D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid >> (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent [[ CCK ]] antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini. what is the relation? antagonist Then the cells were treated with various concentrations of apoE3, lactoferrin and bovine serum albumin with or without 100 microg/ml of GMC, and the << SGLT1 >>-dependent methyl alpha-D-glucopyranoside ([[ AMG ]]) uptake and levels of SGLT1 expression were determined. what is the relation? substrate The positive correlation between << vitamin A >> and immunoglobulin A concentrations might be the result of the vitamin A inductive effect during [[ immunoglobulins A ]] synthesis. what is the relation? upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. what is the relation? agonist-inhibitor Thus, we found that << 5HHMF >> enhances heme oxygenase-1 (HO-1) expression via [[ nuclear factor-erythroid 2-related factor 2 ]] (Nrf2) activation. what is the relation? activator However, only << MDMA >> reduced [[ SERT ]] density. what is the relation? downregulator One exception is tranexamic acid (<< TXA >>), which, as a lysine mimetic, inhibits binding of plasminogen to [[ fibrin ]]. what is the relation? inhibitor OATP1B1-, OATP1B3-, and << OATP2B1 >>-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), [[ silybin B ]] (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively). what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 489,"Regarding the sentence ""Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers << DEX >> inhibited [[ IL-2 ]] production partially and enhanced IL-2R alpha expression and proliferation."", what is the relation? indirect-downregulator Regarding the sentence ""The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]."", what is the relation? agonist-activator Regarding the sentence ""Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (<< Pin1 >>), an enzyme that catalyzes the conversion of the peptide bond of [[ pSer ]]/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification."", what is the relation? substrate Regarding the sentence ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T (<< CT >>), to destroy plasmatic PAI-1 and alpha2-anti[[ plasmin ]]."", what is the relation? downregulator Regarding the sentence ""We now show that mutation of the 769R/ G desensitization site (Lomeli, H.M.J., Melcher, T., Hoger, T., Geiger, J.R., Kuner, T., Monyer, H., Higuchi, M.B.A. and Seeburg, P.H, Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science, 9(266) (1994) 1709-1713) greatly attenuates the << lithium >>-induced potentiation of [[ GluR3 ]]."", what is the relation? activator Regarding the sentence ""<< Amiloride >> is a specific inhibitor of [[ uPA ]] but does not inhibit tPA."", what is the relation? inhibitor Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system."", what is the relation? product-of Regarding the sentence ""Labetalol (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the << isoprenaline >> responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors."", what is the relation? agonist Regarding the sentence ""First, we showed that intracerebroventricular administration of << glucose >> in rats increases [[ DBI ]] expression in hypothalamic glial-like tanycytes."", what is the relation? indirect-upregulator Regarding the sentence ""Differences in magnitude of << Na(+) >>-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in [[ ASCT2 ]] protein expression, this being more abundant in WKY PTE cells."", what is the relation? upregulator Regarding the sentence ""The potent << histamine H(1)-receptor >> antagonist cetirizine ([[ Zyrtec ]]) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine."", what is the relation? antagonist Regarding the sentence ""We have identified 3-hydroxypyridin-2-thione (<< 3-HPT >>) as a novel ZBG that is compatible with [[ HDAC ]] inhibition."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 490,"The ARB << eprosartan >> is a nonbiphenyl nontetrazole [[ angiotensin II type 1 receptor ]] (AT1) antagonist, which acts to decrease total peripheral resistance. Please explain the relation. antagonist At a low pH (pH 7.4), but not pH 7.9, << ifenprodil >> reduces the mean open time of GluN1/[[ GluN2B ]] receptors, which may be responsible for its usefulness as a context-dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic. Please explain the relation. downregulator On the other hand, in patients with a mean serum carvedilol level (Cmin) of less than 2.5 nmol/l up to 2 weeks after the start of<< carvedilol >> therapy, the degree of reduction in the [[ BNP ]] value after the 3rd month was significantly larger, relative to the patient group with Cmin over 2.5 nmol/l. Please explain the relation. indirect-downregulator << Felodipine >> and the p-chloro analogue inhibited Ca2+/calmodulin-dependent [[ caldesmon kinase ]] with similar potencies (IC50 = 17.4 microM), whereas the oxidized and t-butyl analogues caused no inhibition. Please explain the relation. inhibitor In addition, << vinblastine >> induces the DNA-binding activities of the transcription factor [[ NF-κB ]], HSF1, AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins. Please explain the relation. activator Consumption of << alcohol >> for 8weeks induced severe liver damage with increases in prognostic indicators such as aspartate transaminase, [[ alanine transaminase ]] in serum whereas co-administration of CNF suppressed their increases. Please explain the relation. indirect-upregulator Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.). Please explain the relation. upregulator The discovery of an inducible << oxidase >> whose apparent substrate preference is [[ spermine ]] indicates that polyamine catabolism is more complex than that originally proposed. Please explain the relation. substrate << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor RGM-1 cells were treated with << CDCA >> or GW4064, an [[ FXR ]] agonist, in the presence or absence of guggulsterone, an FXR antagonist. Please explain the relation. agonist Depletion of putrescine, << spermidine >>, and spermine by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of [[ ornithine decarboxylase ]] (ODC) that is the first rate-limiting enzyme for polyamine biosynthesis, decreased the apoptotic index. Please explain the relation. product-of The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]]. Please explain the relation. agonist-activator Exposure to mifepristone (a glucocorticoid receptor antagonist), but not << spironolactone >> (a [[ mineralocorticoid receptor ]] antagonist), precluded both the corticosteroid-induced elevation in amiloride-sensitive I(sc) and the induced changes in beta- and gamma-ENaC mRNA. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",11,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",antagonist 491,"Polyclonal antisera to either << b5R >> or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl ([[ NHOH-4-ABP ]]) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP). Please explain the relation. substrate 8-pCPT-2'-O-Me-cAMP-AM potentiation of << insulin >> secretion stimulated by tolbutamide was markedly inhibited by 2-APB (25 μM) and enhanced by the PKC inhibitor [[ bisindolylmaleimide I ]] (1 μM). Please explain the relation. indirect-upregulator << Hydrogen sulphide >> (H(2)S) is synthesized from L-cysteine via the action of cystathionine-gamma-lyase (CSE) and [[ cystathionine-beta-synthase ]] (CBS). Please explain the relation. product-of The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity. Please explain the relation. agonist-activator << HSYA >> treatment also decreased [[ NF-κB ]] p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Please explain the relation. downregulator Although the treatment with MSG increased IRS-1 tyrosine phosphorylation (<< pIRS-1 >>) by 96 % (MSG, 17.02 ± 0.6; control, 8.7 ± 0.2 a.u.), exercise training also increased it in both groups (control, 13.6 ± 0.1; [[ MSG ]], 22.2 ± 1.1 a.u.). Please explain the relation. upregulator db/db mice treated with << DRF 2655 >> showed 5- and 3.6-fold inhibition in phosphoenolpyruvate carboxykinase and [[ glucose 6-phosphatase ]] activity and 651% and 77% increases in the beta-oxidation enzymes carnitine palmitoyltransferase and carnitine acetyltransferase, respectively. Please explain the relation. inhibitor INTRODUCTION: The principal aim of this study was to assess the efficacy of << quinidine >> in suppressing [[ IKr ]] in vitro and in modulating the rate dependence of the QT interval in the ""SQT1"" form of the short QT syndrome. Please explain the relation. indirect-downregulator One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15). Please explain the relation. substrate_product-of It was concluded that << PGE1 >> selectively reduces both N- and R-type Ca2+ currents by activating a [[ G-protein ]] probably through the EP3 receptor in paratracheal ganglion cells. Please explain the relation. activator Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction. Please explain the relation. agonist-inhibitor Synthesis and in Vitro Characterisation of << Ifenprodil >>-Based Fluorescein Conjugates as GluN1/[[ GluN2B ]] N-Methyl-D-aspartate Receptor Antagonists. Please explain the relation. antagonist << Noradrenaline >> and phenylephrine ([[ alpha(1)-adrenoceptor ]] agonist) each produced a concentration-dependent tonic contraction, their pD(2) values being 6.87+/-0.08 and 6.10+/-0.05, respectively. Please explain the relation. agonist The observed inhibition on << IFN-gamma >>, GM-CSF, and IL-3 mRNA was blocked by the selective beta2AR antagonist ICI 118,551 (10(-6) M) and by [[ timolol ]] (10(-6) M), a nonselective antagonist. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 492,"Regarding ""The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating << histamine H1-receptor >> antagonists [[ terfenadine ]], astemizole, loratadine, and acrivastine are reviewed."", can you determine the relation? antagonist Regarding ""The expression of << regucalcin >> is stimulated through the action of insulin in liver cells in vitro and in vivo and it is decreased in the liver of rats with type I diabetes induced by [[ streptozotocin ]] administration in vivo."", can you determine the relation? indirect-downregulator Regarding ""The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE2, and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists << SC-51089 >> (EP1 specific) and AH 6809 ([[ EP1 ]] and EP2 specific)."", can you determine the relation? agonist Regarding ""In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity << Na(+) >>-dependent amino acid transporter, with functional features of [[ ASCT2 ]] transport."", can you determine the relation? upregulator Regarding ""<< Monocarboxylate transporters >> (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, [[ pyruvate ]], as well as ketone bodies."", can you determine the relation? substrate Regarding ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""RESULTS: Ketorolac was six times more active against COX-1 (IC(50) = 0.02 microM) than << COX-2 >> (IC(50) = 0.12 microM) while [[ bromfenac ]] was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than COX-1 (IC(50) = 0.210 microM)."", can you determine the relation? downregulator Regarding ""We have examined the effects on the activities of three calmodulin-dependent enzymes (cAMP phosphodiesterase, caldesmon kinase and myosin light chain kinase) of the dihydropyridine << Ca2+ channel >> blocker [[ felodipine ]] and three analogues (p-chloro, oxidized and t-butyl) exhibiting different pharmacological potencies."", can you determine the relation? inhibitor Regarding ""<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two PtdSer synthases, [[ PSS1 ]] and PSS2."", can you determine the relation? product-of Regarding ""Tissue-type plasminogen activator (tPA), a << serine >> protease well known for generating plasmin, has been demonstrated to induce [[ matrix metalloproteinase-9 ]] (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts."", can you determine the relation? indirect-upregulator Regarding ""Interestingly, << ursolic acid >> increased the phosphorylation of [[ AMPK ]] and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells."", can you determine the relation? activator Regarding ""<< Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to [[ acetylcarnitine ]] and free CoA."", can you determine the relation? substrate_product-of Regarding ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""<< Sorafenib >> induced a cell cycle block and apoptosis in the acute myeloid leukemia cell lines MV4-11 and MOLM-13, both expressing [[ FLT3 ]] with an internal tandem duplication, whereas no effect was observed on four other acute myeloid leukemia cell lines."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 493,"In reference to ""We observed a significant reduction in CSE induced luciferase expression, NF-κB DNA binding, << I-κBε >> degradation and c-Rel nuclear translocation in cells pretreated with [[ vitamin C ]]."", what is the relation? downregulator In reference to ""Inhibitors of << PDE4 >> ([[ rolipram ]]; 0.1-10 microM) and PDE3 (cilostazol; 0.1-10 microM) delayed spontaneous eosinophil apoptosis maximally by 25% and 15%, respectively."", what is the relation? inhibitor In reference to ""<< Cycloxygenase-2 >> (COX-2)-derived prostaglandin E2 ([[ PGE2 ]]) has been shown to be important in esophageal tumorigenesis."", what is the relation? product-of In reference to ""The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists SB224289 (300 microg/kg; 5-HT1B), << BRL15572 >> (300 microg/kg; [[ 5-HT1D ]]), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C)."", what is the relation? antagonist In reference to ""Inhibition of p95ErbB2, p185ErbB2, and EGFR phosphorylation by << GW572016 >> resulted in the inhibition of downstream phospho-Erk1/2, phospho-AKT, and [[ cyclin D ]] steady-state protein levels."", what is the relation? indirect-downregulator In reference to ""Hydrogen sulphide (H(2)S) is synthesized from << L-cysteine >> via the action of cystathionine-gamma-lyase ([[ CSE ]]) and cystathionine-beta-synthase (CBS)."", what is the relation? substrate In reference to ""These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves."", what is the relation? agonist In reference to ""Subsequent analysis revealed that << cucurbitacin I >> strongly activates [[ RhoA ]] and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers."", what is the relation? activator In reference to ""Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor In reference to ""Upon co-exposure to V(5+) and << TCDD >>, V(5+) significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and [[ Cyp1b1 ]] mRNA, protein, and catalytic activity levels at 24 h."", what is the relation? upregulator In reference to ""In general, << rifampicin >> can act on a pattern: rifampicin activates the [[ nuclear pregnane X receptor ]] that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities."", what is the relation? agonist-activator In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of [[ glutamine ]] to oxoglutaramic acid (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""Sitagliptin. << Sitagliptin >>, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and [[ glucose-dependent insulinotropic polypeptide ]]."", what is the relation? indirect-upregulator In reference to ""RESULTS: Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective COX-1/<< COX-2 >> inhibitor, [[ ketorolac ]], resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 494,"Regarding ""One of the enzymes responsible for the production of KA, kynurenine aminotransferase I (<< KATI >>), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", can you determine the relation? substrate_product-of Regarding ""Alprenolol and BAAM also caused surmountable antagonism of << isoprenaline >> responses, and this [[ beta 1-adrenoceptor ]] antagonism was slowly reversible."", can you determine the relation? agonist Regarding ""<< SNP >> inhibits the accumulation of HIF-1alpha, the regulatory subunit of HIF-1, and the transcriptional activation of [[ HIF-1alpha ]] via a mechanism that is not dependent on either NO or soluble guanylate cyclase."", can you determine the relation? indirect-downregulator Regarding ""In addition, cobalt protoporphyrin (<< CoPP >>), a specific [[ HO-1 ]] inducer, predominantly suppressed LPS-induced NO production."", can you determine the relation? activator Regarding ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", can you determine the relation? agonist-activator Regarding ""Both the 5 alpha-reductase inhibitor finasteride and << alpha 1-adrenoceptor >> antagonists (e.g. alfuzosin, doxazosin, [[ prazosin ]], tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials."", can you determine the relation? antagonist Regarding ""Crocin (25 and 50mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of << Bax >>/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by [[ DZN ]]."", can you determine the relation? upregulator Regarding ""These results suggested that << DMBT >> could inhibit invasion and angiogenesis by downregulation of [[ VEGF ]]and MMP-9, resulting from the inhibition of Akt pathway."", can you determine the relation? downregulator Regarding ""A series of xanthine derivatives in which a methylene was inserted at position 8 of << xanthine >> scaffold was synthesized and evaluated as inhibitors of [[ dipeptidyl peptidase 4 ]] (DPP-4) for the treatment of type 2 diabetes."", can you determine the relation? inhibitor Regarding ""Growth inhibition of these tumor cell lines was associated with the dephosphorylation of EGFR, HER2, and HER3, accompanied by the loss of association of HER3 with << phosphatidylinositol 3-kinase >>[[ phosphatidylinositol ]] 3-kinase, and down-regulation of Akt activity."", can you determine the relation? substrate Regarding ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", can you determine the relation? agonist-inhibitor Regarding ""The present results indicated that N-<< BPs >> induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing [[ Bim ]] expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways."", can you determine the relation? indirect-upregulator Regarding ""<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two PtdSer synthases, [[ PSS1 ]] and PSS2."", can you determine the relation? product-of Regarding ""<< Cannabinoid receptor 1 >> (CB(1)) inverse agonists (e.g., [[ rimonabant ]]) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications."", can you determine the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",12,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",agonist-inhibitor 495,"Regarding the sentence ""Nizatidine (<< LY139037 >>), a selective [[ histamine H2-receptor ]] antagonist, is a potent inhibitor of gastric acid secretion."", what is the relation? antagonist Regarding the sentence ""Given these findings, a unified PK model including the inhibition of MAO-A- and << CYP2D6 >>-catalyzed [[ 5-MeO-DMT ]] metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models."", what is the relation? substrate Regarding the sentence ""Further, 5HHMF increased specific DNA-binding activity of << Nrf2 >>, and transient knockdown with Nrf2 siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity."", what is the relation? upregulator Regarding the sentence ""<< HSYA >> suppressed the expression of TLR-4, Myd88, [[ ICAM-1 ]], TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells."", what is the relation? indirect-downregulator Regarding the sentence ""The concentration response to << levcromakalim >> (LEVC), a [[ K(ATP) channel ]] opener, was significantly shifted to the left in the inflamed smooth-muscle cells."", what is the relation? activator Regarding the sentence ""The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas [[ BM ]] and esterified-DEX had full transactivation agonistic activity."", what is the relation? agonist-activator Regarding the sentence ""Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released glutamate and its conversion to << glutamine >> through the enzyme [[ glutamine synthetase ]] (GS)."", what is the relation? product-of Regarding the sentence ""Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction."", what is the relation? agonist-inhibitor Regarding the sentence ""Suppression of Src/<< ERK >> and GSK-3/β-catenin signaling by [[ pinosylvin ]] inhibits the growth of human colorectal cancer cells."", what is the relation? downregulator Regarding the sentence ""The selective << betaAR >> agonist [[ isoproterenol ]] caused an enhancement of hippocampal CA3 network activity, as measured by an increase in frequency of spontaneous burst discharges recorded in the CA3 region."", what is the relation? agonist Regarding the sentence ""Our recent study has demonstrated that coadministration of << monoamine oxidase A >> (MAO-A) inhibitor [[ harmaline ]] (5 mg/kg) increases systemic exposure to 5-MeO-DMT (2 mg/kg) and active metabolite bufotenine."", what is the relation? inhibitor Regarding the sentence ""The beneficial role of << 17beta-estradiol >> on blood pressure, cardiac hypertrophy, vascular [[ osteopontin ]] expression, perivascular fibrosis, and impaired NO-dependent relaxation of isolated aortic rings was completely abrogated by coadministration of medroxyprogesterone acetate."", what is the relation? indirect-upregulator Regarding the sentence ""Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts cortisol to inactive [[ cortisone ]], and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids."", what is the relation? substrate_product-of Regarding the sentence ""<< Fenofibrate >> and GW2331 induced expression of acyl-coenzyme A (CoA) oxidase and [[ enoyl-CoA hydratase ]] and reduced apolipoprotein C-III and phosphoenolpyruvate carboxykinase mRNAs."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",4,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-upregulator 496,"Inhibition studies demonstrated that the methyl group on the << phenylacetic acid >> ring is required for [[ COX-2 ]] selectivity. Please explain the relation. inhibitor << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of [[ acetyl-CoA ]] and carnitine to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of Taken together, these data demonstrate that baicalin inhibits the metabolism of << DXM >> in a concentration-dependent manner in rats, possibly through inhibiting hepatic [[ CYP2D ]] and CYP3A activities. Please explain the relation. substrate In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of << WIN 55,212 >> antagonized by the [[ CB2 ]] antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]. Please explain the relation. agonist The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (<< NF-κB >>) genes expression in [[ cisplatin ]] injected rats. Please explain the relation. indirect-downregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor << DEX >> enhanced the ratio [[ IFN-gamma ]]/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). Please explain the relation. upregulator << ACTH >>-stimulated peak cortisol, delta cortisol, and [[ delta DHEA ]]-S levels are decreased during hyperthyroidism, probably due to increased turnover. Please explain the relation. product-of There was also an increase in c-kit, Trio, Rho-A, << Rac-3 >>, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells. Please explain the relation. indirect-upregulator Activation of endogenous somatostatin receptor subtype 2 (<< sst2 >>) by [[ somatostatin-14 ]] or activation of transiently transfected rat D2 dopamine receptors (rD2(long)) by quinpirole had no effect. Please explain the relation. activator Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, ketanserin (10 microM), a 5-HT2 antagonist, << thioperamide >> (10 microM), a [[ histamine H3 ]] antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect. Please explain the relation. antagonist Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of << inducible nitric-oxide synthase >> by [[ 15-deoxy-Delta12,14-prostaglandin J2 ]]. Please explain the relation. downregulator The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. Please explain the relation. agonist-activator This effect was prevented by rapamycin, an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1), or by << PF470867 >>, a selective inhibitor of the p70 ribosomal S6 kinase 1 ([[ S6K1 ]]). Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 497,"In reference to ""Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, << nuclear factor-kappaB >> and activating protein-1, which were increased in [[ fructose ]]-fed rats."", what is the relation? upregulator In reference to ""Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (SCF), and macrophage migration inhibitory factor (<< MIF >>)) were down-regulated by [[ artemisinic acid ]]."", what is the relation? indirect-downregulator In reference to ""Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor << manumycin A >> caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing [[ hApoA-I ]] and cholesterol ester transfer protein transgenes."", what is the relation? indirect-upregulator In reference to ""The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine."", what is the relation? agonist-activator In reference to ""<< Glyphosate >> affects aromatic amino acid biosynthesis by inhibiting 5-enolpyruvylshikimate-3-phosphate synthase ([[ EPSPS ]])."", what is the relation? inhibitor In reference to ""One of the enzymes responsible for the production of KA, << kynurenine aminotransferase I >> (KATI), also catalyses the reversible transamination of glutamine to [[ oxoglutaramic acid ]] (GTK, EC 2.6.1.15)."", what is the relation? substrate_product-of In reference to ""RESULTS: << Ketorolac >> was six times more active against COX-1 (IC(50) = 0.02 microM) than COX-2 (IC(50) = 0.12 microM) while bromfenac was approximately 32 times more active against COX-2 (IC(50) = 0.0066 microM) than [[ COX-1 ]] (IC(50) = 0.210 microM)."", what is the relation? downregulator In reference to ""In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]."", what is the relation? agonist-inhibitor In reference to ""The effects of D-1997 in the basilar artery were not modified by incubation with either the << 5-HT2 receptor >> antagonist [[ ketanserin ]] (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM)."", what is the relation? antagonist In reference to ""In addition to affecting << DAT >> function, MDMA rapidly decreased vesicular [[ DA ]] transport as assessed in striatal vesicles prepared from treated rats."", what is the relation? substrate In reference to ""The results reinforce previous assumptions that << dopamine >> may interact with eicosanoid metabolism by means of [[ D(2) receptor ]] activation, and implicate an involvement of cPLA(2) and COX-2 in this effect."", what is the relation? activator In reference to ""In the DRN, << brexpiprazole >> completely inhibited the firing of 5-HT neurons via [[ 5-HT1A ]] agonism and was more potent than aripiprazole (ED50 = 230 and 700 mug/kg, respectively)."", what is the relation? agonist In reference to ""Cytochrome P450 epoxygenase 2J2 (<< CYP2J2 >>) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ([[ EETs ]]), which possess various beneficial effects on the cardiovascular system."", what is the relation? product-of In reference to ""In HaCaT cells, << buthanol >> and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm(2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 ([[ COX-2 ]]), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF- α)."", what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator 498,"The selective << beta1AR >> antagonists atenolol and metoprolol blocked [[ isoproterenol ]]-induced enhancement, with apparent K(b) values of 85 +/- 36 and 3.9 +/- 1.7 nM, respectively. Please explain the relation. agonist However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both MAO-A and << MAO-B >> by [[ tranylcypromine ]] together with the monoamine precursors. Please explain the relation. inhibitor There was also an increase in c-kit, Trio, << Rho-A >>, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the [[ parathion ]]-treated cells. Please explain the relation. indirect-upregulator Binding of the agonist angiotensin II (AngII) and inverse agonist << losartan >> in wild-type [[ AT1R ]] changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific ""lid"" conformations of ECL2. Please explain the relation. agonist-inhibitor Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (<< SCF >>), and macrophage migration inhibitory factor (MIF)) were down-regulated by [[ artemisinic acid ]]. Please explain the relation. indirect-downregulator << ATP-binding cassette transporter A1 >> is involved in hepatic [[ alpha-tocopherol ]] secretion. Please explain the relation. product-of << Carnitine acetyltransferases >> (CrAT) catalyze the reversible conversion of acetyl-CoA and [[ carnitine ]] to acetylcarnitine and free CoA. Please explain the relation. substrate_product-of To determine whether 3,4-methylenedioxymethamphetamine (<< MDMA >>)-induced reductions in [[ SERT ]] density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered to rats, and brain serotonin and SERT density were measured. Please explain the relation. downregulator The esterified-BM, however, had only partial transactivation agonistic activity in cells transfected with << rat GR >>, whereas BM and esterified-[[ DEX ]] had full transactivation agonistic activity. Please explain the relation. agonist-activator The enzyme << dimethylarginine dimethylaminohydrolase >> (DDAH) specifically hydrolyzes these asymmetrically methylated [[ arginine ]] residues to citrulline and methylamines. Please explain the relation. substrate Further, 5HHMF increased specific DNA-binding activity of << Nrf2 >>, and transient knockdown with Nrf2 siRNA subsequently reversed [[ 5HHMF ]]-induced NO inhibition, which was followed by suppression of HO-1 activity. Please explain the relation. upregulator Together, our findings suggest the critical role of 'Rac and subsequent activation of << phospholipase A2 >>' in [[ ceramide ]]-signalling to nucleus. Please explain the relation. activator BACKGROUND: << Pranlukast >>, a [[ cysteinyl leukotriene receptor 1 ]] (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation. Please explain the relation. antagonist Cabozantinib (<< XL184 >>) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, [[ AXL ]], and FLT3. Please explain the relation. Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",7,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",inhibitor 499,"<< GCS >> therapy results in reduced mRNA expression of interleukin-4 ([[ IL-4 ]]) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma. what is the relation? indirect-downregulator << CCl(4) >> administration triggered inflammatory response in mice livers by activating [[ nuclear factor-kappaB ]] (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). what is the relation? activator In conclusion, fenoterol-induced constitutive << beta(2)-adrenoceptor >> activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist [[ timolol ]]. what is the relation? agonist-inhibitor << Agmatine >>, locally synthesized, is an endogenous agonist at [[ imidazoline receptors ]], a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter. what is the relation? agonist Type 2 11β-hydroxysteroid dehydrogenase encoded by the << HSD11B2 >> gene converts [[ cortisol ]] to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. what is the relation? substrate_product-of Adenylosuccinate synthetase (<< AdSS >>) catalyzes the [[ Mg2+ ]] dependent condensation of a molecule of IMP with aspartate to form adenylosuccinate, in a reaction driven by the hydrolysis of GTP to GDP. what is the relation? substrate Humans with << FSH beta >> gene mutations tend to have a more severe phenotype than those with FSHR gene mutations, although infertility and varying degrees of impaired sex [[ steroid ]] production occur in both types of mutations. what is the relation? product-of Pretreatment of the splenocytes with both BPB and AACOCF3 suppressed << phorbol 12-myristate 13-acetate >> plus ionomycin-induced [[ IL-2 ]] secretion in a concentration-dependent manner. what is the relation? upregulator CONCLUSIONS: In the maximum registered dosage, << nabumetone >> inhibits thromboxane production much more than meloxicam, signifying less [[ COX-2 ]] selectivity of the former. what is the relation? downregulator In contrast, the selective << beta2AR >> antagonists [[ ICI-118,551 ]] and butoxamine inhibited isoproterenol-mediated enhancement with apparent low affinities (K(b) of 222 +/- 61 and 9268 +/- 512 nM, respectively). what is the relation? antagonist RESULTS: << DRF 2655 >> showed concentration-dependent transactivation of [[ PPARalpha ]] and PPARgamma. what is the relation? agonist-activator << S1P >> activated phosphatidylinositol 3-kinase ([[ PI3K ]])/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells. what is the relation? indirect-upregulator A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase ([[ CEase ]]) and acetylcholinesterase (AChE). what is the relation? inhibitor 13cisRA and ROAc, but not << 4HPR >>, caused a dose-dependent reduction in plasma [[ osteocalcin ]], an effect that correlated with retinoid-induced bone effects. what is the relation? Options: product-of, substrate_product-of, indirect-downregulator, activator, indirect-upregulator, substrate, upregulator, inhibitor, agonist-activator, downregulator, agonist, antagonist, agonist-inhibitor",2,"['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']",indirect-downregulator