Evangelista S, Maggi C A
Pharmacology Department, Menarini Pharmaceuticals, Firenze, Italy.
Br J Pharmacol. 1991 Jan;102(1):119-22. doi: 10.1111/j.1476-5381.1991.tb12142.x.
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.
我们研究了静脉注射胆囊收缩素-8（CCK-8）和其他肽类对用氨基甲酸乙酯麻醉的大鼠经胃灌注25%乙醇后胃损伤形成的影响。2. 静脉注射CCK-8（50 - 100 nmol kg-1）可诱导对乙醇所致胃出血性损伤的保护作用，而蛙皮素（1 - 100 nmol kg-1）、降钙素基因相关肽（1 - 50 nmol kg-1）、神经激肽A（1 μmol kg-1）或P物质（100 nmol kg-1）则无此作用。3. CCKA拮抗剂L-364,718（2.45 μmol kg-1，静脉注射）增加了乙醇诱导的损伤指数，并逆转了CCK-8（50 nmol kg-1，静脉注射）的保护作用。CCKB拮抗剂L-365,260（5 μmol kg-1，静脉注射）和较低剂量的L-364,718（0.25 μmol kg-1，静脉注射）无效。4. 在迷走神经切断的大鼠中未观察到CCK-8（50 nmol kg-1，静脉注射）的胃保护作用，且辣椒素预处理可使其降低。与载体预处理的大鼠相比，辣椒素预处理的大鼠经乙醇灌注后胃损伤加重。5. 这些结果表明，CCK-8的黏膜保护作用至少部分涉及CCKA受体的激活，并由迷走神经辣椒素敏感纤维介导。
