Effects of Omeprazole and Cimetidine on Gastric Acid Secretion and Right Atrial Beating Frequency in Isolated Organ Preparations from the Guinea Pig

Abstract

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^-6mol/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 ∼ 5 × 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 × 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.