Ethanol regulation of gamma-aminobutyric acid A receptors: genomic and nongenomic mechanisms.
Ethanol regulation of gamma-aminobutyric acid A receptors: genomic and nongenomic mechanisms.
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发表时间：
2004
影响因子：
13.5
通讯作者：
Sandeep Kumar;Rebekah L. Fleming;A. Morrow
中科院分区：
文献类型：
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作者：
Sandeep Kumar;Rebekah L. Fleming;A. Morrow
γ -氨基丁酸(A) （GABA(A)）受体是配体门控离子通道，主要介导中枢神经系统的抑制性突触传递。这些受体是五聚体复合物，由几个亚基组成（α, β, γ, δ,），每个亚基由几个同工异构体组成。慢性乙醇消耗改变GABA(A)受体功能，产生细胞对GABA和乙醇的耐受性，对苯二氮卓类药物和巴比妥类药物的交叉耐受性，以及对反向激动剂的敏化。近年来的研究清楚地表明，GABA(A)受体在乙醇依赖中起重要作用，长期给药后GABA(A)受体的功能特性发生改变。然而，长期给药后GABA(A)受体功能改变的确切机制尚未得到解决。GABA(A)受体对慢性乙醇暴露的适应机制可能涉及乙醇诱导的细胞表面表达、亚细胞定位、突触定位、受体磷酸化、神经类固醇和/或GABA(A)受体亚基组成的变化。在这篇综述中，我们提供了最近的数据有关的机制，可能负责改变GABA(A)受体的性质和表达在慢性乙醇管理的概述。
gamma-Aminobutyric acid(A) (GABA(A)) receptors are ligand-gated ion channels that, predominantly, mediate inhibitory synaptic transmission in the CNS. These receptors are pentameric complexes that are comprised of subunits from several classes (alpha, beta, gamma, delta, ), with each class consisting of several isoforms. Chronic ethanol consumption alters GABA(A) receptor function producing cellular tolerance to GABA and ethanol, cross-tolerance to benzodiazepines and barbiturates, and sensitization to inverse agonists. Recent studies have clearly demonstrated that GABA(A) receptors play an important role in ethanol dependence and functional properties of GABA(A) receptor are altered following chronic ethanol administration. However, the exact mechanisms that account for alterations in GABA(A) receptor function following chronic ethanol administration have not been resolved. The mechanisms responsible for adaptation of GABA(A) receptors to chronic ethanol exposure may involve ethanol-induced changes in cell surface expression, subcellular localization, synaptic localization, receptor phosphorylation, neurosteroids, and/or changes in GABA(A) receptor subunit composition. In this review, we provide an overview of recent data pertaining to mechanisms that could be responsible for altered properties and expression of GABA(A) receptors following chronic ethanol administration.