Intracerebroventricular injection of clonidine releases β-endorphin to induce mucosal protection in the rat
Intracerebroventricular injection of clonidine releases β-endorphin to induce mucosal protection in the rat
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DOI：
10.1016/s0028-3908(99)00195-1
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Fürst, S
中科院分区：
文献类型：
--
作者：
Gyires, K;Rónai, AZ;Fürst, S
探讨可乐定对中枢神经系统（CNS）的胃保护作用可能与内源性阿片系统有关。侧脑室注射（i. c. v.）注射可乐定（470 pmol/大鼠）在大鼠中以显著的方式抑制由（口服给药）酸化乙醇诱导的胃粘膜损伤。中枢给药可乐定的胃保护作用被i.c.v或脑池内（i.c.）给予突触前α-2肾上腺素受体拮抗剂育亨宾;非选择性阿片受体拮抗剂纳洛酮;和δ阿片受体拮抗剂纳曲吲哚。这些结果表明，中枢α-2肾上腺素受体和内源性阿片系统之间的相互作用参与介导的粘膜保护作用。β-内啡肽抗血清（i.c.）也拮抗由脑室内注射可乐定诱导的胃保护作用，表明β-内啡肽释放可能是可乐定胃保护作用的关键因素。此外，i. c. v.或i.c.注射β-内啡肽产生皮摩尔范围的有效胃保护作用。迷走神经切断后可乐定的粘膜保护作用消失，表明中枢效应可能通过迷走神经传出传递到外周。由于阿托品（1 mg/kg i. v.）未能改变，但六甲铵（10 mg/kg i. v.）拮抗可乐定的胃保护作用，似乎在外周烟碱型而非毒蕈碱型胆碱能受体可能参与可乐定的粘膜保护作用。总之，可乐定（i. c. v.）通过释放内源性阿片样物质-最可能是β-内啡肽-在大鼠中诱导胃保护作用。可乐定的中枢胃保护作用需要迷走神经通路的完整性，外周胆碱能烟碱受体可能介导该作用，而非毒蕈碱受体。(C)2000爱思唯尔科技有限公司版权所有。
The possibility that the endogenous opioid system could be involved in the central nervous system (CNS)-mediated gastroprotective effect of clonidine was investigated. Intracerebroventricularly (i.c.v.) injected clonidine (470 pmol/rat) inhibited the gastric mucosal lesions induced by (orally administered) acidified ethanol in a significant manner in the rat. The gastroprotective effect of the centrally administered clonidine was antagonised by i.c.v, or intracisternally (i.c.) administered presynaptic alpha-2 adrenoceptor antagonist, yohimbine; the non-selective opioid receptor antagonist, naloxone; and the delta opioid receptor antagonist naltrindole. These results suggest that an interaction between central alpha-2 adrenoceptors and endogenous opioid systems is involved in mediating the mucosal protective effect. beta-endorphin antiserum (i.c.) also antagonised the gastroprotection induced by intracerebroventricularly injected clonidine indicating that beta-endorphin release is likely to be a key factor in the gastroprotective effect of clonidine. Furthermore, the i.c.v. or i.c. injection of beta-endorphin produced a potent gastroprotection in the picomolar range. The mucosal protective effect of clonidine was abolished after vagotomy indicating that the central effect may be conveyed to the periphery by vagal efferents. Since atropine (1 mg/kg i.v.) failed to modify, but hexamethonium (10 mg/kg i.v.) antagonised the gastroprotective effect of clonidine, it would appear that in the periphery nicotinic, but not muscarinic, cholinergic receptors are likely to be involved in the mucosal protective effect of clonidine. In conclusion, clonidine (i.c.v.) induces gastroprotective action by releasing an endogenous opioid substance - most likely beta-endorphin - in the rat. The clonidine-induced central gastroprotection requires the integrity of vagal pathway; cholinergic nicotinic - but not muscarinic - receptors might mediate the effect in the periphery. (C) 2000 Elsevier Science Ltd. All rights reserved.