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- W2155196734 abstract "Abstract Acid secretion is conducted by the parietal cell of the gastric mucosa. The H + ,K + -ATPase has been shown to be specifically located to this cell and during recent years been recognized as the gastric proton pump. Omeprazole, a known inhibitor of acid secretion, administered in vivo was found to bind specifically to the H + ,K + -ATPase of the rabbit gastric mucosa. A stoichiometry of 2.1 mol radiolabel per mol phosphoenzyme was calculated at total inhibition of the H + ,K + -ATPase enzyme activity. In isolated gastric glands prepared from omeprazole-treated animals, the secretagogue-induced increase in oxygen consumption, related to acid secretion, was inhibited to the same level as the H + ,K + -ATPase activity. Both the degree of acid secretion inhibition induced by omeprazole and the amount of inhibitor bound to the H + ,K + -ATPase were found to be dependent on the stimulation state of the parietal cell. Inhibition of secretion by the H 2 -receptor blocker ranitidine prior to omeprazole treatment prevented both the inhibition of H + , K + -ATPase and oxygen consumption normally observed with omeprazole and, furthermore, reduced the binding levels of radiolabel to the enzyme. Inhibition of acid secretion by the H + , K + -ATPase inhibitor SCH 28080 totally prevented the binding of radiolabel to the H + , K + -ATPase. The inhibition by omeprazole could be fully reversed in gastric glands and H + ,K + ATPase isolated from omeprazole-treated animals by addition of β-mercaptoethanol. The major product formed during reactivation was the reduced form of omeprazole, compound H 168/22. Neutralization of the gastric glands in vitro with imidazole totally prevented the inhibitory action of omeprazole. These experiments demonstrate the necessity of acid for the inhibition of gastric acid secretion by omeprazole and the binding of the inhibitor to the H + ,K + -ATPase, both in vivo and in vitro , and also the specificity of omeprazole for the H + ,K + -ATPase." @default.
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- W2155196734 date "1989-01-01" @default.
- W2155196734 modified "2023-09-26" @default.
- W2155196734 title "Specific Labelling of Gastric H+,K+-ATPase by Omeprazole" @default.
- W2155196734 doi "https://doi.org/10.3109/00365528909091265" @default.
- W2155196734 hasPublicationYear "1989" @default.
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