Exogenous and endogenous cholecystokinin protects gastric mucosa against the damage caused by ethanol in rats.

Cholecystokinin (CCK) shows a potent influence on gastric secretion and motility but its role in gastric mucosal integrity has been little examined. In this study we found that exogenous CCK octapeptide protected gastric mucosa against ethanol-induced gastric injury but was ineffective against aspirin-induced damage. The protective effects of CCK were dose-dependent and almost completely reversed by pretreatment with the specific CCKA receptor antagonist, loxiglumide, while the CCKB receptor antagonist, L-365,260, was not effective. The CCK-induced protection against ethanol injury was accompanied by a significant increase in gastric blood flow. The inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester attenuated the gastroprotection and gastric hyperemia induced by CCK while the concurrent treatment with L-arginine, but not D-arginine restored the protective activity of CCK and the accompanying increase in gastric blood flow. Endogenous CCK released by intraduodenal instillation of oleate prevented the formation of acute gastric lesions induced by both ethanol and aspirin and the protective effects were abolished by pretreatment with loxiglumide. We conclude that CCK exerts protective activity against ethanol-induced damage and that this effect is mediated through specific CCKA receptors and hyperemia involving NO.