Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The half maximal inhibitory concentrations (IC50) of substituted benzimidazoles for the H+, K(+)-ATPase in hog gastric vesicles were measured by using the pyruvate kinase-lactate dehydrogenase-linked system in which hydrolysis of ATP was coupled with the oxidation of NADH. The vesicles were incubated in a solution containing a high concentration of KCl, valinomycin and Mg-ATP, and the intravesicular medium was acidified. The inhibitor was activated in the acidic medium and reacted with SH groups on the luminal (intravesicular) side of the ATPase. The active compound formed in the extravesicular medium (pH 6.11) was quenched by GSH. Under these conditions, IC50 of new compound E3810, 2[(4-(3-methoxypropoxy)-3-methylpyridine-2-yl)methyl-sulfinyl]-1H- benzimidazole sodium salt, was 0.072 microM and that of omeprazole was 0.47 microM at 25 degrees. On the other hand, the rates of formation of active compounds, tetracyclic sulfenamide derivatives, from original substituted benzimidazoles in 0.1 N HCl (k) were determined by measuring optical density at the characteristic wavelengths of the active compounds. There was a good correlation between IC50 and k for various substituted benzimidazoles including E3810, methoxy derivative of E3810, omeprazole, Ro 18-5364, H compound, picoprazole and timoprazole. This fact suggest that the rate of the formation of the acid-activated compound is a main factor determining the potency of the inhibitor.
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PMID:The potency of substituted benzimidazoles such as E3810, omeprazole, Ro 18-5364 to inhibit gastric H+, K(+)-ATPase is correlatedwith the rate of acid-activation of the inhibitor. 215 89

The sulfoxide Ro 18-5364, a potential metabolite of the IND Ro 18-5362, is a powerful inhibitor of gastric mucosal (H+ + K+)-ATPase, decreasing enzymatic activity with an apparent Ki of 0.1 microM. Exposure of Ro 18-5364-treated gastric membranes to dithiothreitol fully restored (H+ + K+)-ATPase activity. ATP protected the enzyme against Ro 18-5364-induced inactivation of enzymatic activity. In addition, Ro 18-5364 inhibited vesicular proton uptake. In proton translocation experiments reduced lipoic acid methyl ester partially restored transport properties. Dithiothreitol and mercaptoethanol were without effect. The results are discussed with respect to the possible location of essential sulfhydryl groups for enzyme activity and proton transport.
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PMID:Gastric (H+ + K+)-ATPase: modulation of the inhibitory properties of the novel potent antisecretagogue Ro 18-5364 by sulfhydryl reagents and nucleotides. 300 40

The sulfoxide agent Ro 18-5364 is an extremely potent and rapid inhibitor of the gastric mucosal (H+ + K+)-ATPase with an apparent Ki of 0.1 microM at pH 6. The inhibition of both enzymatic activity and vesicular proton transport in membrane preparations is concentration- and time-dependent. Comparative studies with the two enantiomers of Ro 18-5364 indicated no enantiomeric preference. Marked differences were seen between Ro 18-5364 (sulfoxide) and Ro 18-5362 (sulfide) with regard to inhibitory activity. Even at concentrations as high as 0.1 mM Ro 18-5362 failed to affect significantly (H+ + K+)-ATPase activity and associated proton translocation. Similarly, Ro 17-5380 demonstrated an apparent Ki of 20 microM for inhibition of the (H+ + K+)-ATPase whereas its reduced derivative Ro 17-4749 was inactive. Addition of a single methyl group in the pyridine moiety of Ro 18-5364 noticeably decreased the inhibitory potency. The inhibitory action of Ro 18-5364 on (H+ + K+)-ATPase activity was markedly higher at low incubation medium pH in comparison to physiological or alkaline values. The results of incorporation studies paralleled that of enzymatic inhibition. The extent of Ro 18-5364 incorporation was dependent on time, concentration, and medium hydrogen ion concentration, with a decrease in medium pH resulting in increased binding. While ATP and GTP had little effect on the binding rates, reduced lipoic acid methyl ester, mercaptoethanol and dithiothreitol were capable of displacing the radiolabel to different extents. Autoradiography of electrophoresed Ro-18-5364-labeled gastric microsomal membranes confirmed that the radiolabel was associated with polypeptides of approximately 100 kDa. The incorporation was reversed upon subjection of the membranes to reducing conditions.
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PMID:Ro 18-5364, a potent new inhibitor of the gastric (H+ + K+)-ATPase. 303 41

1. Cimetidine was more potent 4 hr after a single injection of 25 or 100 mg/kg body wt in increasing gastric pH than other H2 receptor antagonists, ranitidine and famotidine but was less efficient than H+/K(+)-ATPase inhibitors. Omeprazole rose proventricular and gizzard pH at a lower dose than SCH 28080 and Ro 18-5364 (30, 50 and 200 mg/kg body wt, respectively). 2. Proventricular and gizzard pH values were maximal 1 and 4 hr after a single injection of 7.5 mumol/kg body wt omeprazole. Inhibition of acid secretion was maintained for 24 hr after an injection of 100 mumol/kg. 3. H+/K(+)-ATPase activity in vitro was 10 mumol Pi/hr/mg protein in the microsomal fractions of the proventriculus. It was doubled by nigericine and inhibited by SCH 28080. However, western blots by high specific H+/K(+)-ATPase monoclonal antibody 95-A3 and 95-111 recognized a 42 kDa band but hardly exhibited the specific 95 kDa band recognition. 4. Chickens and immature pullets showed a higher H+/K(+)-ATPase activity than laying hens. Calcium level of the diet did not affect the enzyme activity but coarse particles of calcium fed to pullets or laying hens enhanced the H+/K(+)-ATPase activity when compared with ground particles.
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PMID:Gastric acid secretion in the chicken: effect of histamine H2 antagonists and H+/K(+)-ATPase inhibitors on gastro-intestinal pH and of sexual maturity calcium carbonate level and particle size on proventricular H+/K+ ATPase activity. 790 2