Ivermectin:: A positive allosteric effector of the α7 neuronal nicotinic acetylcholine receptor

被引：250
作者：
Krause, RM
Buisson, B
Bertrand, S
Corringer, PJ
Galzi, JL
Changeux, JP
Bertrand, D [1 ]
机构：
[1] Univ Geneva, Ctr Med, Dept Physiol, CH-1211 Geneva 4, Switzerland
[2] Inst Pasteur, URA CNRS D1284, F-75724 Paris 15, France
来源：
MOLECULAR PHARMACOLOGY | 1998年 / 53卷 / 02期
关键词：
D O I：
10.1124/mol.53.2.283
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
We report that preapplication of ivermectin, in the micromolar range, strongly enhances the subsequent acetylcholine-evoked current of the neuronal chick or human alpha 7 nicotinic acetylcholine receptors reconstituted in Xenopus laevis oocytes and K-28 cells. This potentiation does not result from nonspecific Cl- currents. The concomitant increase in apparent affinity and cooperativity of the dose-response curve suggest that ivermectin acts as a positive allosteric effector. This interpretation is supported by the observation of an increase in efficiency of a partial agonist associated with the potentiation and by the differential effect of ivermectin on mutants within the M2 channel domain. Ivermectin effects reveal a novel allosteric site for pharmacological agents on neuronal alpha 7 nicotinic acetylcholine receptors.
引用
收藏
页码：283 / 294
页数：12
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