Effect of omeprazole on gastric secretion in H+,K+-ATPase and in pepsinogen-rich cell fractions from rabbit gastric mucosa.

In order to study the effects of the substituted benzimidazole omeprazole on gastric secretory functions, parietal cells and chief cells from rabbit gastric mucosa were separated and enriched by density gradient centrifugation in Percoll. H+,K+-ATPase activity, as well as a 100,000 dalton protein, was found to copurify with a cell fraction morphologically characterized as mainly parietal cells (purity approximately 65%), while pepsinogen copurified with a cell fraction morphologically characterized as chief cells (purity approximately 90%). A spontaneous pepsinogen release (9.9 micrograms/mg cell dry wt X 2 hr), unaffected by both atropine and omeprazole, was found in the chief cell fraction. The release was approximately doubled by both carbacholine (4 X 10(-5)M) and dibutyryl cAMP (db-cAMP, 10(-3)M). The cholinergic stimulation was selectively blocked by atropine, while omeprazole had no effect on pepsinogen release induced by either of the secretagogues. On the other hand, omeprazole inhibited both db-cAMP- and histamine-stimulated acid secretion quantified as [14C]aminopyrine (AP) accumulation in the parietal cell fraction. Cimetidine counteracted only acid secretion induced by histamine. These findings indicate that omeprazole has a specific effect on acid secretion, and are consonant with the hypothesis that the effect is due to H+,K+-ATPase inhibition.