Brzozowski Tomasz, Konturek Peter C, Sliwowski Zbigniew, Drozdowicz Danuta, Burnat Grzegorz, Pajdo Robert, Pawlik Michal, Bielanski Wladyslaw, Kato Ikuo, Kuwahara Atsuzakau, Konturek Stanislaw J, Pawlik Wieslaw W
Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
Regul Pept. 2008 Jun 5;148(1-3):6-20. doi: 10.1016/j.regpep.2008.02.003. Epub 2008 Feb 20.
Orexin-A, identified in the neurons and endocrine cells in the gut, has been implicated in control of food intake and sleep behavior but little is known about its influence on gastric secretion and mucosal integrity. The effects of orexin-A on gastric secretion and gastric lesions induced in rats by 3.5 h of water immersion and restraint stress (WRS) or 75% ethanol were determined. Orexin-A (5-80 microg/kg i.p.) increased gastric acid secretion and attenuated gastric lesions induced by WRS and this was accompanied by the significant rise in plasma orexin-A, CGRP and gastrin levels, the gastric mucosal blood flow (GBF), luminal NO concentration and an increase in mRNA for CGRP and overexpression of COX-2 protein and the generation of PGE(2) in the gastric mucosa. Orexin-A-induced protection was abolished by selective OX-1 receptor antagonist, vagotomy and attenuated by suppression of COX-1 and COX-2, deactivation of afferent nerves with neurotoxic dose of capsaicin, pretreatment with CCK(2)/gastrin antagonist, CGRP(8-37) or capsazepine and by inhibition of NOS with L-NNA. This study shows for the first time that orexin-A exerts a potent protective action on the stomach of rats exposed to non-topical ulcerogens such as WRS or topical noxious agents such as ethanol and these effects depend upon hyperemia mediated by COX-PG and NOS-NO systems, activation of vagal nerves and sensory neuropeptides such as CGRP released from sensory nerves probably triggered by an increase in gastric acid secretion induced by this peptide.
食欲素A在肠道的神经元和内分泌细胞中被发现，它与食物摄入和睡眠行为的控制有关，但对其对胃分泌和黏膜完整性的影响知之甚少。本研究测定了食欲素A对大鼠胃分泌以及由3.5小时水浸束缚应激（WRS）或75%乙醇诱导的胃损伤的影响。腹腔注射食欲素A（5 - 80微克/千克）可增加胃酸分泌，并减轻WRS诱导的胃损伤，同时伴随着血浆食欲素A、降钙素基因相关肽（CGRP）和胃泌素水平显著升高，胃黏膜血流量（GBF）、管腔一氧化氮（NO）浓度增加，以及胃黏膜中CGRP的mRNA表达增加、COX - 2蛋白过表达和前列腺素E2（PGE2）生成。选择性OX - 1受体拮抗剂、迷走神经切断术可消除食欲素A诱导的保护作用，抑制COX - 1和COX - 2、用神经毒性剂量的辣椒素使传入神经失活、用胆囊收缩素2（CCK(2)）/胃泌素拮抗剂、CGRP(8 - 37)或辣椒平预处理以及用L - NNA抑制一氧化氮合酶（NOS）可减弱该保护作用。本研究首次表明，食欲素A对暴露于非局部溃疡原（如WRS）或局部有害剂（如乙醇）的大鼠胃具有强大的保护作用，这些作用依赖于由COX - 前列腺素（PG）和NOS - NO系统介导的充血、迷走神经激活以及感觉神经释放的感觉神经肽（如CGRP），而这可能是由该肽诱导的胃酸分泌增加所触发的。
