Lüddens H, Korpi E R
Center for Molecular Biology, University of Heidelberg, Germany.
J Psychiatr Res. 1995 Mar-Apr;29(2):77-94. doi: 10.1016/0022-3956(94)00040-x.
gamma-Aminobutyric acid (GABA) is the most prominent of the inhibiting neurotransmitters in the brain. It exerts its main action through GABAA receptors. The receptors respond to the presence of GABA by the opening of an intrinsic anion channel. Hence, they belong to the molecular superfamily of ligand-gated ion channels. There exist in the brain multiple GABAA receptors that show differential distribution and developmental patterns. The receptors presumably form by the assembly of five proteins from at least three different subunits (alpha 1-6, beta 1-3 and gamma 1-3). The regulation of functional properties by benzodiazepine (BZ) receptor ligands, neurosteroids, GABA and its analogs differs dramatically with the alpha variant present in the complex. Additional variation of the GABAA receptors comes with the exchange of the gamma subunits. No clear picture exists for the role of the beta subunits, though they may play an important part in the sensitivity of the channel-receptor complex. The effects of BZ receptor ligands on animal behavior range from agonist effects, e.g. anxiolysis, sedation, and hypnosis, to inverse agonist effects, e.g. anxiety, alertness, and convulsions. The diversity of effects reflects the ubiquity of the GABAA/BZ receptors in the brain. Recent data provide some insight into the mechanism of action of BZ ligands, but no clear delineation can be drawn from a single ligand to a single behavioral effect. This may be due to the fact that intrinsic efficacies of the ligands differ between receptor subtypes, so that the diversity of native receptors is further complicated by the diversity of the mode the ligands act on GABAA receptor subtypes. The behavioral actions of alcohol (ethanol) are similar to those produced by GABAA receptor agonists. In agreement, alcohol-induced potentiation of GABAergic responses has often been observed at behavioral, electrophysiological and biochemical levels. Thus, there is clearly a GABAA-dependent component in the actions of alcohol. However, the site and mode of action of ethanol on GABAA/BZ receptors remain controversial.
γ-氨基丁酸（GABA）是大脑中最主要的抑制性神经递质。它通过GABAA受体发挥主要作用。这些受体通过开启一个内在的阴离子通道对GABA的存在做出反应。因此，它们属于配体门控离子通道的分子超家族。大脑中存在多种GABAA受体，它们表现出不同的分布和发育模式。这些受体可能由至少三种不同亚基（α1 - 6、β1 - 3和γ1 - 3）中的五种蛋白质组装而成。苯二氮䓬（BZ）受体配体、神经甾体、GABA及其类似物对功能特性的调节因复合物中存在的α变体而有显著差异。GABAA受体的额外变异来自γ亚基的交换。虽然β亚基可能在通道 - 受体复合物的敏感性中起重要作用，但关于其作用尚无清晰的认识。BZ受体配体对动物行为的影响范围从激动剂效应，如抗焦虑、镇静和催眠，到反向激动剂效应，如焦虑、警觉和惊厥。效应的多样性反映了GABAA/BZ受体在大脑中的广泛存在。最近的数据为BZ配体的作用机制提供了一些见解，但无法从单一配体明确推断出单一行为效应。这可能是由于配体的内在效能在受体亚型之间存在差异，因此天然受体的多样性因配体作用于GABAA受体亚型的模式多样性而进一步复杂化。酒精（乙醇）的行为作用与GABAA受体激动剂产生的作用相似。与此一致的是，在行为、电生理和生化水平上经常观察到酒精诱导的GABA能反应增强。因此，酒精的作用中显然存在GABAA依赖性成分。然而，乙醇对GABAA/BZ受体的作用位点和作用方式仍存在争议。
