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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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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? 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

product-of

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

substrate

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-downregulator

<< 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-upregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

agonist-inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

antagonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

activator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

agonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-upregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-upregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

product-of

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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. 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

activator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-upregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

antagonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

activator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

substrate

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-upregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

activator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 Pretreatment of the tissues with combined << 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

<< 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-upregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

activator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

antagonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

substrate

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

agonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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. 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

substrate

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

substrate

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

substrate

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

agonist-activator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

antagonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 << 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

product-of

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

<< 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

product-of

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 << 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 << 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

antagonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

antagonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

inhibitor

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-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. 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "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 <or=10.5%] while on glimepiride alone or in combination with metformin.", describe the relation. inhibitor Given the text "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.", 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

antagonist

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "<< 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

product-of

<< 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

activator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 "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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

downregulator

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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

product-of

<< 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

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: 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

['product-of', 'substrate_product-of', 'indirect-downregulator', 'activator', 'indirect-upregulator', 'substrate', 'upregulator', 'inhibitor', 'agonist-activator', 'downregulator', 'agonist', 'antagonist', 'agonist-inhibitor']

indirect-upregulator