PROTECTION INDUCED BY CHOLECYSTOKININ-8 (CCK-8) IN ETHANOL-INDUCED GASTRIC-LESIONS IS MEDIATED VIA VAGAL CAPSAICIN-SENSITIVE FIBERS AND CCKA RECEPTORS

1 We have investigated the effect of intravenous injection of cholecystokinin-8 (CCK-8) and other peptides on gastric lesion formation in response to an intragastric perfusion with 25% ethanol in rats anaesthetized with urethane. 2 Intravenous injection of CCK-8 (50-100 nmol kg-1), but not bombesin (1-100 nmol kg-1), calcitonin gene-related peptide (1-50 nmol kg-1), neurokinin A (1-mu-mol kg-1) or substance P (100 nmol kg-1), induced protection against gastric haemorrhagic lesions produced by ethanol. 3 The CCK(A)-antagonist L-364,718 (2.45-mu-mol kg-1, i.v.) increased the lesion index induced by ethanol and reversed the protective effect of CCK-8 (50 nmol kg-1, i.v.). The CCK(B)-antagonist L-365,260 (5-mu-mol kg-1, i.v.) and a lower dose of L-364,718 (0.25-mu-mol kg-1, i.v.) were ineffective. 4 The gastric protective effects afforded by CCK-8 (50 nmol kg-1, i.v.) were not observed in vagotomized-rats and were reduced by capsaicin pretreatment. In capsaicin-pretreated rats there was a worsening of gastric lesions induced by ethanol-perfusion as compared to those observed in vehicle-pretreated rats. 5 These results demonstrate that the mucosal protective effect of CCK-8 involves, at least in part, the activation of CCK(A)-receptors and is mediated by vagal capsaicin-sensitive fibres.