Muscarinic stimulation of inositol phosphate accumulation and acid secretion in gastric fundic mucosal cells.
The muscarinic agonist, carbachol (CCh), was shown to stimulate the production of inositol phosphates (IP) in isolated cells from rabbit fundic mucosa. This stimulatory effect was time- and dose-dependent: EC50 values for IP1, IP2 and IP3 accumulation were not statistically different. The mean value was 30 +/- 8 microM (n = 6). The corresponding maximal stimulation (% of basal value) observed after 20 min incubation in the presence of 100 microM CCh was 160 +/- 15%. CCh-induced IP accumulation was abolished by atropine (Ki = 0.32 +/- 0.18 nM (n = 3)). The CCh concentrations leading to half-maximal inhibition of N-[3H]methylscopolamine binding and half-maximal IP accumulation were similar. The half-maximal value for CCh-induced aminopyrine accumulation was 8-times lower. These results indicate that IP3-mediated mobilization of intracellular Ca2+ might be involved in CCh-induced acid secretion by parietal cells.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005748:Gastric Fundus; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013403:Sugar Phosphates / Q000378:metabolism*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D013403:Sugar Phosphates; D002217:Carbachol; D002118:Calcium