Effects of antimuscarinic agents and prostaglandin E2 on the gastric mucosal lesions induced by necrotizing agents and water-immersion stress in rats.

The role of antimuscarinic action in gastric mucosal protection against necrotizing agents and the role of such mucosal protection in antiulcerogenic action were studied in rats with i.v. administered antimuscarinic agents. Pirenzepine, as well as PGE2, prevented the gastric mucosal lesions induced by all necrotizing agents (99.5% ethanol, 0.6 N HCI, 0.15 N NaOH, 0.4 N HCI-50 mM taurocholate), but atropine did not prevent the HCI-induced lesions. Cimetidine inhibited only the ethanol-induced lesions even at the antisecretory dose. Higher doses of pirenzepine (5-fold) and atropine (10-fold) were required to inhibit the gastric secretion in Shay rats than in vagally stimulated rats. There was no difference between the antisecretory doses of cimetidine in Shay rats and vagally stimulated rats. PGE2 (0.03-0.1 mg/kg) did not affect gastric secretion. The protective doses of pirenzepine and atropine against mucosal lesions induced by necrotizing agents were similar to the dose in inhibiting vagally stimulated acid secretion and water-immersion stress-induced lesions. PGE2 (100 micrograms/kg) did not prevent the water-immersion stress induced gastric lesions. These results suggested that antimuscarinic agents protect the gastric mucosa from necrotizing agents via a blocking action on the activation of the intrinsic cholinergic nerve. However, antiulcerogenic action is more deeply concerned with antisecretory action than cytoprotection.