Gastric cytoprotection by pirenzepine in rats: evaluating method for cytoprotective activity by antisecretory agents

The effects of antisecretory agents, pirenzepine, atropine and cimetidine, on gastric mucosal lesions induced in rats by ethanol, HCI (0.6 N), HCI-acidified 50% ethanol and HCI-acidified 50 mM sodium taurocholate (TCA) were comparatively studied with PGE2. The involvement of gastric acid in the formation of ethanol-induced necrosis was also studied. PGE2 and pirenzepine inhibited necrosis induced by all necrotizing agents at the non-antisecretory doses, and the cytoprotective effect of pirenzepine was not abolished by indomethacin. Atropine and cimetidine did not inhibit HCI-induced necrosis even at the antisecretory dose. Atropine and cimetidine at the antisecretory dose inhibited necrosis induced by ethanol, but did not inhibit the red streaks. The ethanol-induced necrosis was also inhibited by neutralizing intragastric H+ with Tris buffer. In gastric fistula rats, alkalinization of the lumen was observed by exposure to ethanol, but necrosis was not produced. There is a close relationship between the necrosis and intragastric acid. Thus it is assumed that gastric acid is involved in the formation of ethanol-induced necrosis. It was suggested that pirenzepine possesses cytoprotective action which is not related to endogenous PGs. On the other hand, the antiulcer actions of atropine and cimetidine may be due, in a part, to antisecretory effects.