Necessity of intracellular cyclic AMP in inducing gastric acid secretion via muscarinic M 3 and cholecystokinin 2 receptors on parietal cells in isolated mouse stomach

Abstract

The existence of a direct action of acetylcholine and gastrin on muscarinic M 3 and cholecystokinin 2 (CCK 2) receptors on gastric parietal cells has not yet been convincingly established because these stimulated acid secretions are remarkably inhibited by histamine H 2 receptor antagonists. In the present study, we investigated the necessity of intracellular cyclic AMP in inducing gastric acid secretion via muscarinic M 3 and CCK 2 receptors on parietal cells using an isolated mouse stomach preparation. Bethanechol (10–300 μM) produced a marked increase in acid output and this increase was completely blocked by famotidine (10 μM). In the presence of famotidine, bethanechol (1–30 μM) augmented the acid secretory response to dibutyryl AMP (200 μM) in a concentration-dependent manner. The augmentation was blocked by atropine (1 μM), 4-DAMP (0.1 μM), a muscarinic M 3-selective antagonist, and by Ca 2+ exclusion from the serosal nutrient solution. Pentagastrin (0.3–3 μM) also concentration-dependently stimulated gastric acid secretion, but the effect was completely inhibited by famotidine. In the presence of famotidine, pentagastrin (0.1–0.3 μM) elicited a definite potentiation of the acid secretory response to dibutyryl cyclic AMP (200 μM). This potentiation was inhibited by YM022 (1 μM), a CCK 2 receptor antagonist, and by exclusion of Ca 2+ from the serosal nutrient solution. The present results suggest that gastric acid secretion via the activation of muscarinic M 3 and CCK 2 receptors on the parietal cells is induced by activation of the cyclic AMP-dependent secretory pathway.