Olsen R W, Tobin A J
Department of Pharmacology, School of Medicine, University of California, Los Angeles 90024.
FASEB J. 1990 Mar;4(5):1469-80. doi: 10.1096/fasebj.4.5.2155149.
The major type of receptor for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), called the GABAA receptor, is a member of a gene superfamily of ligand-gated ion channels. This receptor is a hetero-oligomeric protein composed of several distinct polypeptide types (alpha, beta, gamma, and delta). Molecular cloning of these polypeptides reveals that they show 20-40% identity with each other, and 10-20% identity with polypeptides of the nicotinic acetylcholine receptors and strychnine-sensitive glycine receptor. Each polypeptide type is also represented by a family of genes whose members have 60-80% amino acid sequence identity. Regions of conserved and variable amino acid sequence suggest structural and functional domains within each polypeptide. All of the polypeptides when expressed in heterologous cells produce GABA-activated chloride channels, and the different subtypes express different pharmacological properties. The distributions of mRNAs for the different GABAA receptor polypeptides and their subtypes show significant brain regional variation consistent with pharmacological and biochemical evidence for receptor heterogeneity. Subpopulations of GABAA receptors with different cellular and regional locations show differential sensitivity to GABA, to modulators like steroids, to physiological regulation, to disease processes, and to pharmacological manipulation by drugs such as benzodiazepines. The properties of the different subpopulations of GABAA receptors are determined by which one or more of the different polypeptides and their subtypes are expressed in a given cell to produce a variety of different oligomeric protein structures. Molecular cloning techniques have produced rapid advances in understanding the GABAA receptor protein family.
抑制性神经递质γ-氨基丁酸（GABA）的主要受体类型称为GABAA受体，它是配体门控离子通道基因超家族的成员。该受体是一种异源寡聚蛋白，由几种不同的多肽类型（α、β、γ和δ）组成。这些多肽的分子克隆显示它们彼此之间有20%-40%的同源性，与烟碱型乙酰胆碱受体和士的宁敏感型甘氨酸受体的多肽有10%-20%的同源性。每种多肽类型也由一个基因家族代表，其成员具有60%-80%的氨基酸序列同源性。保守和可变氨基酸序列区域表明每个多肽内的结构和功能域。所有多肽在异源细胞中表达时都会产生GABA激活的氯离子通道，不同的亚型表现出不同的药理学特性。不同GABAA受体多肽及其亚型的mRNA分布显示出明显的脑区差异，这与受体异质性的药理学和生化证据一致。具有不同细胞和区域定位的GABAA受体亚群对GABA、对类固醇等调节剂、对生理调节、对疾病过程以及对苯二氮䓬类药物等药物的药理操作表现出不同的敏感性。GABAA受体不同亚群的特性取决于在给定细胞中表达的是哪一种或多种不同的多肽及其亚型，以产生各种不同的寡聚蛋白结构。分子克隆技术在理解GABAA受体蛋白家族方面取得了快速进展。
