Protection induced by cholecystokinin-8 (CCK-8) in ethanol-induced gastric lesions is mediated via vagal capsaicin-sensitive fibres and CCKA receptors.
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 mumol kg-1) or substance P (100 nmol kg-1), induced protection against gastric haemorrhagic lesions produced by ethanol. 3. The CCKA-antagonist L-364,718 (2.45 mumol 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 CCKB-antagonist L-365,260 (5 mumol kg-1, i.v.) and a lower dose of L-364,718 (0.25 mumol 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 CCKA-receptors and is mediated by vagal capsaicin-sensitive fibres.
Evangelista
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Pharmacology Department, Menarini Pharmaceuticals, Firenze, Italy.
Maggi
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CA
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D020109:Devazepide; D000431:Ethanol; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012683:Sensory Deprivation / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D000431:Ethanol; D020109:Devazepide; D012844:Sincalide; D002211:Capsaicin