可的松：豚鼠离体回肠中一种有效的γ-氨基丁酸A型（GABAA）拮抗剂。

Cortisone: a potent GABAA antagonist in the guinea-pig isolated ileum.

作者信息

Ong J, Kerr D I, Capper H R, Johnston G A

机构信息

Department of Pharmacology, University of Sydney, N.S.W. Australia.

出版信息

J Pharm Pharmacol. 1990 Sep;42(9):662-4. doi: 10.1111/j.2042-7158.1990.tb06629.x.

DOI:10.1111/j.2042-7158.1990.tb06629.x

PMID:1981909

Abstract

In the guinea-pig isolated ileum, cortisone at 0.001-10 nM induced a non-competitive, dose-dependent antagonism of GABAA-receptor-mediated contractile responses to applied GABA, depressing the maximum contractile response to GABA (100 microM), without affecting contractile responses to acetylcholine or cholinergic twitch contractions. At higher concentrations (greater than 10 nM), cortisone depressed contractile responses to acetylcholine (10-100 nM) and cholinergic twitch responses to transmural stimulation. Cortisone is thus the most potent non-competitive antagonist at GABAA-receptor complexes in the guinea-pig ileum. From molecular modelling, sterically there appeared little difference between cortisone and cortisol, the latter being an enhancer of GABAA-receptor-mediated action in the ileum. However, there were significant differences in electrostatic potentials between the two steroids, due to the different levels of oxidation at C11 which may contribute to such opposing actions.

摘要

在豚鼠离体回肠中，0.001 - 10 nM的可的松对应用的GABA所介导的收缩反应产生非竞争性、剂量依赖性拮抗作用，抑制对GABA（100 microM）的最大收缩反应，而不影响对乙酰胆碱或胆碱能抽搐收缩的反应。在较高浓度（大于10 nM）时，可的松抑制对乙酰胆碱（10 - 100 nM）的收缩反应以及对跨壁刺激的胆碱能抽搐反应。因此，可的松是豚鼠回肠中GABAA受体复合物最有效的非竞争性拮抗剂。从分子模型来看，可的松和皮质醇在空间结构上差异不大，后者是回肠中GABAA受体介导作用的增强剂。然而，由于C11位氧化水平不同，这两种类固醇的静电势存在显著差异，这可能导致了这种相反的作用。