EXOGENOUS AND ENDOGENOUS CHOLECYSTOKININ PROTECTS GASTRIC-MUCOSA AGAINST THE DAMAGE CAUSED BY ETHANOL IN RATS

Cholecystokinin (CCK) shows a potent influence on gastric secretion an d motility but its role in gastric mucosal integrity has been little e xamined. In this study we found that exogenous CCK octapeptide protect ed gastric mucosa against ethanol-induced gastric injury but was ineff ective against aspirin-induced damage. The protective effects of CCK w ere dose-dependent and almost completely reversed by pretreatment with the specific CCKA receptor antagonist, loxiglumide, while the CCKB re ceptor antagonist, L-365,260, was not effective. The CCK-induced prote ction against ethanol injury was accompanied by a significant increase in gastric blood flow. The inhibition of nitric oxide (NO) synthase b y N-G-nitro-L-arginine methyl ester attenuated the gastroprotection an d gastric hyperemia induced by CCK while the concurrent treatment with L-arginine, but not D-arginine restored the protective activity of CC K and the accompanying increase in gastric blood flow. Endogenous CCK released by intraduodenal instillation of oleate prevented the formati on of acute gastric lesions induced by both ethanol and aspirin and th e protective effects were abolished by pretreatment with loxiglumide. We conclude that CCK exerts protective activity against ethanol-induce d damage and that this effect is mediated through specific CCKA recept ors and hyperemia involving NO.