Konturek S J, Brzozowski T, Pytko-Polonczyk J, Drozdowicz D
Institute of Physiology, Jagiellonian University School of Medicine, Krakow, Poland.
Eur J Pharmacol. 1995 Jan 24;273(1-2):57-62. doi: 10.1016/0014-2999(94)00674-v.
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.
胆囊收缩素（CCK）对胃分泌和运动有强大影响，但其在胃黏膜完整性中的作用鲜有研究。在本研究中，我们发现外源性CCK八肽可保护胃黏膜免受乙醇诱导的胃损伤，但对阿司匹林诱导的损伤无效。CCK的保护作用呈剂量依赖性，且用特异性CCKA受体拮抗剂洛西肽预处理几乎可完全逆转这种作用，而CCKB受体拮抗剂L-365,260则无效。CCK诱导的对乙醇损伤的保护作用伴随着胃血流量的显著增加。NG-硝基-L-精氨酸甲酯抑制一氧化氮（NO）合酶可减弱CCK诱导的胃保护作用和胃充血，而同时用L-精氨酸（而非D-精氨酸）处理可恢复CCK的保护活性及伴随的胃血流量增加。十二指肠内注入油酸释放的内源性CCK可预防乙醇和阿司匹林诱导的急性胃损伤形成，且洛西肽预处理可消除这种保护作用。我们得出结论，CCK对乙醇诱导的损伤具有保护活性，且这种作用是通过特异性CCKA受体和涉及NO的充血介导的。
