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Effects of omeprazole and cimetidine on gastric acid secretion and right atrial beating frequency in isolated organ preparations from the guinea pig.

The effects of omeprazole , a substituted benzimidazole, on gastric acid secretion and on right atrial beating frequency have been investigated in guinea pig preparations in vitro. Cimetidine was used as a reference compound. Omeprazole , at 10(-6) mol/l, inhibited basal acid secretion, whereas cimetidine, at 10(-5) mol/l, did not. There were also differences in the effects on stimulated secretion. Cimetidine (10(-5) mol/l) competitively inhibited histamine-stimulated acid secretion without affecting the maximal histamine response. In contrast, omeprazole concentration dependently depressed (EC50 approximately 5 X 10(-7) mol/l) the maximal histamine response without any effect on the histamine sensitivity. Furthermore, dibutyryl-cAMP-stimulated acid secretion was inhibited by omeprazole but not by cimetidine. The inhibitory effect of omeprazole (2 X 10(-6) mol/l) on histamine-stimulated acid secretion was reversed by repeated washing of the serosal side of the mucosa. Omeprazole was devoid of histamine H2 receptor antagonistic activity, since it had no effect on the chronotropic response to histamine in the guinea pig right atrium. It is concluded that omeprazole inhibits gastric acid secretion by a non-histaminergic, reversible mechanism and that the site of action is beyond the cAMP step within the parietal cell.