Krause R M, Buisson B, Bertrand S, Corringer P J, Galzi J L, Changeux J P, Bertrand D
Department of Physiology, University Medical Center, 1211 Geneva 4, Switzerland.
Mol Pharmacol. 1998 Feb;53(2):283-94. doi: 10.1124/mol.53.2.283.
We report that preapplication of ivermectin, in the micromolar range, strongly enhances the subsequent acetylcholine-evoked current of the neuronal chick or human alpha7 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 alpha7 nicotinic acetylcholine receptors.
我们报告称，在微摩尔范围内预先应用伊维菌素，可强烈增强随后由乙酰胆碱诱发的、重构于非洲爪蟾卵母细胞和K - 28细胞中的鸡或人神经元α7烟碱型乙酰胆碱受体的电流。这种增强作用并非由非特异性氯离子电流导致。剂量反应曲线的表观亲和力和协同性同时增加，表明伊维菌素作为一种正变构效应剂发挥作用。与增强作用相关的部分激动剂效率增加的观察结果以及伊维菌素对M2通道结构域内突变体的差异效应，均支持这一解释。伊维菌素的作用揭示了一种新型的药物变构位点，存在于神经元α7烟碱型乙酰胆碱受体上。
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