Background: Cholecystokinin (CCK) and gastrin show a potent influence on gastric secretion and motility, but their role in mucosal integrity has been little studied.
Methods: In this study the effects of CCK-8, pentagastrin, and duodenal oleate on acute gastric lesions induced by 100% ethanol were studied in rats.
Results: CCK-8 was about 13 times more potent than pentagastrin in protecting the gastric mucosa against ethanol damage. CCK released by duodenal oleate also protected gastric mucosa against this damage. The protective effects of CCK-8 were almost completely abolished by the blockage of CCK-A receptors with loxiglumide, whereas the protective effect of pentagastrin was completely abolished by L-365,260. The protective effects of CCK, pentagastrin, or duodenal oleate against ethanol injury were accompanied by a marked increase in luminal content of somatostatin, suggesting that this peptide is implicated in this protection. The protective activity of CCK and pentagastrin against ethanol injury was accompanied by a significant increase in gastric blood flow. Inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine methyl ester abolished almost completely both gastric protection and hyperemia induced by CCK and pentagastrin. Addition of L-arginine, but not D-arginine, restored the protective and hyperemic effects of CCK and pentagastrin. Pretreatment with the sulfhydryl blocking agent N-ethylmaleimide also abolished the protective and hyperemic effects of CCK and pentagastrin. The hyperemia, but not the protection, afforded by CCK and pentagastrin was reduced after sensory nerve deactivation with capsaicin.
Conclusions: Both exogenous and endogenous CCK and pentagastrin exert protective activity against ethanol damage, and this effect is mediated through separate receptors, NO, and sulfhydryl-sensitive pathway.