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中枢γ-氨基丁酸A型(GABAA)兴奋性受体和γ-氨基丁酸B型(GABAB)抑制性受体调节大鼠胃酸分泌。

Central GABAA excitatory and GABAB inhibitory receptors regulate gastric acid secretion in rats.

作者信息

Del Tacca M, Blandizzi C, Bernardini M C

机构信息

Laboratory of Molecular Pharmacology, University of Pisa, Italy.

出版信息

Eur J Pharmacol. 1990 Feb 27;177(3):189-94. doi: 10.1016/0014-2999(90)90269-c.

Abstract

The present study investigates the effects of GABAA- and GABAB-receptor agonists and antagonists on gastric secretion after their i.c.v. administration to conscious pylorus-ligated rats and anaesthetized stomach lumen-perfused rats. Muscimol was without effect in pylorus-ligated rats, whereas baclofen produced a significant decrease in acid secretion, which was fully prevented by phaclofen. Under these conditions, a significant decrease in acid secretion was also obtained with bicuculline. In stomach lumen-perfused rats, muscimol caused a marked, dose-dependent increase in acid secretion, which was antagonized by bicuculline. Under the same conditions, baclofen induced a moderate, but significant, bicuculline-sensitive increase in acid secretion. Overall, our results suggest the presence of two central GABA pathways which mediate opposite effects: (a) a bicuculline-sensitive GABAA-receptor, the stimulation of which increases acid secretion under pharmacological depression of central vagal tone (anaesthetized rats); (b) a phaclofen-sensitive GABAB-receptor, the activation of which decreases vagally stimulated acid secretion (pylorus-ligated rats).

摘要

本研究调查了γ-氨基丁酸A型(GABAA)和γ-氨基丁酸B型(GABAB)受体激动剂及拮抗剂经脑室内注射给予清醒的幽门结扎大鼠和麻醉的胃腔灌注大鼠后对胃液分泌的影响。蝇蕈醇对幽门结扎大鼠没有作用,而巴氯芬可使胃酸分泌显著减少,这种作用可被氯苯氨丁酸完全阻断。在这些条件下,荷包牡丹碱也可使胃酸分泌显著减少。在胃腔灌注大鼠中,蝇蕈醇可引起胃酸分泌显著的、剂量依赖性增加,这种作用可被荷包牡丹碱拮抗。在相同条件下,巴氯芬可诱导胃酸分泌适度但显著增加,且对荷包牡丹碱敏感。总体而言,我们的结果表明存在两条介导相反作用的中枢γ-氨基丁酸途径:(a)对荷包牡丹碱敏感的GABAA受体,在中枢迷走神经张力受药物抑制的情况下(麻醉大鼠),刺激该受体可增加胃酸分泌;(b)对氯苯氨丁酸敏感的GABAB受体,激活该受体可减少迷走神经刺激引起的胃酸分泌(幽门结扎大鼠)。

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