Brzozowski Tomasz, Konturek Peter C, Drozdowicz Danuta, Konturek Stanislaw J, Pawlik Michal, Sliwowski Zbigniew, Pawlik Wieslaw W, Hahn Eckhart G
Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzcka Street, 31-531 Cracow, Poland.
Inflammopharmacology. 2005;13(1-3):45-62. doi: 10.1163/156856005774423971.
Ghrelin, identified in the gastric mucosa, has been involved in the control of food intake and growth hormone (GH) release, but whether this hormone influences the gastric secretion and gastric mucosal integrity has been little elucidated. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without suppression of nitric oxide (NO)-synthase or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by the H2-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. In addition, the gastric mucosal expression of mRNA for CGRP, the most potent neuropeptide released from the sensory afferent nerves, was analyzed in rats exposed to WRS with or without ghrelin pre-treatment. Ghrelin (5-80 microg/kg i.p. or 0.6-5 microg/kg i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS. This protective effect was accompanied by a significant rise in the gastric mucosal blood flow (GBF), luminal NO concentration and plasma ghrelin and gastrin levels. Ghrelin-induced protection was abolished by vagotomy and significantly attenuated by L-NNA and deactivation of afferent nerves with neurotoxic dose of capsaicin. The signal for CGRP mRNA was significantly increased in gastric mucosa exposed to WRS as compared to that in the intact gastric mucosa and this was further enhanced in animals treated with ghrelin. We conclude that central and peripheral ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol or WRS, and these effects depend upon vagal activity and hyperemia mediated by the NOS-NO system and CGRP released from sensory afferent nerves.
胃黏膜中发现的胃饥饿素参与了食物摄入和生长激素（GH）释放的调控，但这种激素是否影响胃分泌和胃黏膜完整性却鲜有阐明。我们比较了腹腔注射（i.p.）和脑室内注射（i.c.v.）胃饥饿素对大鼠胃分泌以及由75%乙醇或3.5小时水浸束缚应激（WRS）诱导的胃损伤的影响，实验中还涉及一氧化氮（NO）合酶抑制或辣椒素对传入感觉神经的功能消融。通过平面测量法测定胃损伤的数量和面积，用H₂气体清除法评估胃黏膜血流量（GBF），并采集血液测定血浆胃饥饿素和胃泌素水平。此外，在接受或未接受胃饥饿素预处理的WRS大鼠中，分析感觉传入神经释放的最有效神经肽降钙素基因相关肽（CGRP）的胃黏膜mRNA表达。胃饥饿素（腹腔注射5 - 80微克/千克或脑室内注射0.6 - 5微克/千克）增加胃酸分泌并减轻乙醇和WRS诱导的胃损伤。这种保护作用伴随着胃黏膜血流量（GBF）、管腔NO浓度以及血浆胃饥饿素和胃泌素水平的显著升高。迷走神经切断术消除了胃饥饿素诱导的保护作用，L - NNA以及神经毒性剂量辣椒素使传入神经失活显著减弱了这种保护作用。与完整胃黏膜相比，暴露于WRS的胃黏膜中CGRP mRNA信号显著增加，在用胃饥饿素处理的动物中这一信号进一步增强。我们得出结论，中枢和外周胃饥饿素对暴露于乙醇或WRS的大鼠胃具有强大的保护作用，这些作用依赖于迷走神经活动以及由NOS - NO系统介导的充血和感觉传入神经释放的CGRP。
