Omeprazole: Mode of Action and Effect on Acid Secretion in Animals

H+,K+-ATPase constitutes the final step in the acid secretory process that takes place in the parietal cell, and this enzyme has recently been recognized as a target for inhibitors of acid secretion. The gastric H+,K+-ATPase is located in the uniquely acidic environment of the parietal cell. Omeprazole, a weak base, is concentrated within the acid canaliculus of the parietal cell and is rapidly converted to an inhibitor of the H+,K+-ATPase in the acid compartments of the parietal cell. Omeprazole is thus activated close to its target enzyme, where it is present in high concentrations, and binds selectively to the gastric H+,K+-ATPase. Omeprazole is the first H+,K+-ATPase inhibitor to be used in the treatment of acid-related diseases, and inhibition of acid secretion is closely correlated to inhibition of gastric H+,K+-ATPase activity. Both basal and stimulated acid secretion are inhibited by omeprazole in a dose-dependent manner, irrespective of the nature of the stimulus. Omeprazole exerts a prolonged antisecretory effect, and in dogs, 4 days are required for return to normal acid secretion following a maximal inhibitory dose.