Mixed antagonistic effects of bilobalide at ρ1 GABAC receptor

被引：9

作者：

Huang, SH

Duke, RK ^{[1
]}

Chebib, M

Sasaki, K

Wada, K

Johnston, GAR

机构：

[1] Univ Sydney, Dept Pharmacol D06, Fac Med, Adrien Albert Lab Med Chem, Sydney, NSW 2006, Australia

[2] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia

[3] Hlth Sci Univ Hokkaido, Dept Hyg Chem, Fac Pharmaceut Sci, Ishikari, Hokkaido 0610293, Japan

来源：

NEUROSCIENCE | 2006年 / 137卷 / 02期

基金：

英国医学研究理事会;

关键词：

picrotoxinin; bilobalide; mixed antagonist; use-dependent action; GABAc receptors; two-electrode voltage clamp;

D O I：

10.1016/j.neuroscience.2005.08.071

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Bilobalide was found to be a moderately potent antagonist with a weak use-dependent effect at recombinant human rho(1) GABA(C) receptors expressed in Xenopus oocytes using two-electrode voltage clamp methodology. Antagonism of bilobalide at homomeric rho(1) GABA(C) receptors appeared to be mixed. At low concentration, bilobalide (3 mu M) caused a parallel right shift and surmountable GABA maximal response of the GABA dose-response curve characteristic of a competitive antagonist. At high concentrations, bilobalide (10-100 mu M) caused nonparallel right shifts and reduced maximal GABA responses of GABA dose-response curves characteristic of a noncompetitive antagonist. The potency of bilobalide appears to be dependent on the concentrations of GABA and was more potent at lower GABA concentrations. The mechanism of action of bilobalide at p, GABA(C) receptors appears to be similar to that of the chloride channel blocker picrotoxinin. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.

引用

页码：607 / 617

页数：11

共 49 条

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