Nagata K, Huang C S, Hamilton B J, Carter D B, Narahashi T
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
Brain Res. 1996 Oct 28;738(1):131-7. doi: 10.1016/0006-8993(96)00775-5.
We have recently demonstrated by patch clamp experiments that the four isomers of hexachlorocyclohexane (HCH), alpha-, beta-, gamma- and delta-HCH insecticides, modulated the kinetics of the GABAA receptor-chloride channel complex of rat dorsal root ganglion neurons. The present paper reports the differential effects of HCH isomers of the GABA-induced chloride currents in three combinations of alpha, beta and gamma subunits of GABAA receptor expressed in human embryonic kidney cells. When co-applied with GABA, gamma-HCH strongly suppressed the peak amplitude of GABA-induced current, and delta-HCH strongly enhanced it in the alpha 1 beta 2 gamma 2s, alpha 1 beta 2, alpha 6 beta 2 gamma 2s combinations in a dose-dependent manner. There was little or no difference in the dose dependence of the effects between gamma- and delta-HCH in any of the three subunit combinations. However, alpha- and beta-HCH showed differential effects on GABA-induced chloride currents in the three subunit combinations tested. alpha-HCH showed enhancing effects on the peak current in alpha 1 beta 2 gamma 2s, small enhancing effects on alpha 1 beta 2, and biphasic effects on alpha 6 beta 2 gamma 2s subunit combinations. beta-HCH had little or no effect on the peak current in alpha 1 beta 2 gamma 2s and alpha 1 beta 2 combinations, but suppressed currents in the alpha 6 beta2 gamma 2s subunit combination in a dose-dependent manner. The differential actions of HCH isomers may produce variable effects on different regions of the nervous systems and in different species of animals.
我们最近通过膜片钳实验证明，六氯环己烷（HCH）的四种异构体，即α-、β-、γ-和δ-HCH杀虫剂，可调节大鼠背根神经节神经元GABAA受体-氯离子通道复合物的动力学。本文报道了HCH异构体对人胚肾细胞中表达的GABAA受体α、β和γ亚基三种组合中GABA诱导的氯离子电流的不同影响。当与GABA共同应用时，γ-HCH强烈抑制GABA诱导电流的峰值幅度，而δ-HCH在α1β2γ2s、α1β2、α6β2γ2s组合中以剂量依赖性方式强烈增强该电流。在三种亚基组合中的任何一种中，γ-和δ-HCH之间的效应剂量依赖性几乎没有差异。然而，α-和β-HCH在测试的三种亚基组合中对GABA诱导的氯离子电流表现出不同的影响。α-HCH对α1β2γ2s中的峰值电流有增强作用，对α1β2有小的增强作用，对α6β2γ2s亚基组合有双相作用。β-HCH对α1β2γ2s和α1β2组合中的峰值电流几乎没有影响，但在α6β2γ2s亚基组合中以剂量依赖性方式抑制电流。HCH异构体的不同作用可能会对神经系统的不同区域和不同动物物种产生不同的影响。
