Omeprazole: mode of action and effect on acid secretion in animals.

Stomach acid is generated by the parietal cell of the gastric mucosa. During the last two decades an enzyme called H+,K+-ATPase, has been discovered and shown to be the agent responsible for acid transport in the parietal cell. H+,K+-ATPase is thus the hydrogen ion pump of the stomach. Omeprazole is the first example of a clinically useful inhibitor of H+,K+-ATPase. In animals and in man, omeprazole has been shown to effectively antagonize gastric acid secretion, irrespective of the stimulus used to activate acid formation. Omeprazole was found to have a long duration of antisecretory effect. For a dose that initially gave near maximal inhibition of secretion, four days were required in order to restore the normal secretory rate. Extensive mechanism studies showed that omeprazole specifically bound to H+,K+-ATPase of the gastric mucosa. Furthermore, a parallel inhibition of both maximal acid secretion and of mucosal H+,K+-ATPase activity was found. These data strongly suggested that omeprazole inhibited acid secretion by blockade of H+,K+-ATPase. Studies on the chemical mechanism for inhibition of the pump revealed that omeprazole is concentrated in the acid canaliculus of the parietal cell due to its weak base properties. In acid, omeprazole is rearranged into a sulfenamide derivative which reacts with luminal sulfhydryl groups of the H+,K+-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)