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

摘要

The existence of a direct action of acetylcholine and gastrin on muscarinic M-3 and cholecystokinin(2) (CCK2) 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 CCK2 receptors on parietal cells using an isolated mouse stomach preparation. Bethanechol (10-300 mu M) produced a marked increase in acid output and this increase was completely blocked by famotidine (10 mu M). In the presence of famotidine, bethanechol (1-30 mu M) augmented the acid secretory response to dibutyryl AMP (200 mu M) in a concentration-dependent manner. The augmentation was blocked by atropine (1 mu M), 4-DAMP (0.1 mu M), a muscarinic M-3-selective antagonist, and by Ca2+ exclusion from the serosal nutrient solution. Pentagastrin (0.3-3 mu M) 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 mu M) elicited a definite potentiation of the acid secretory response to dibutyryl cyclic AMP (200 mu M). This potentiation was inhibited by YM022 (1 mu M), a CCK2 receptor antagonist, and by exclusion of Ca2+ from the serosal nutrient solution. The present results suggest that gastric acid secretion via the activation of muscarinic M-3 and CCK2 receptors on the parietal cells is induced by activation of the cyclic AMP-dependent secretory pathway. (c) 2005 Elsevier Inc. All rights reserved.