GABA(A) receptors: structure, function, pharmacology, and related disorders.
GABA(A) receptors: structure, function, pharmacology, and related disorders.
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GABA（A）受体：结构、功能、药理学及相关疾病。
DOI：
10.1186/s43141-021-00224-0
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发表时间：
2021-08-21
期刊：
影响因子：
--
通讯作者：
Hussein DEE
中科院分区：
文献类型：
--
作者：
Ghit A;Assal D;Al-Shami AS;Hussein DEE
γ-氨基丁酸A亚型受体（GABAARs）是中枢神经系统中最重要的抑制性神经递质受体。它们是具有重要生理和治疗意义的配体门控离子通道家族。GABAAR是由19个亚基组成的杂五聚体：6个α（α 1 -6）、3个β（β 1 -3）、3个γ（γ 1 -3）、3个ρ（ρ 1 -3），以及δ（δ）、ε（π）、π（π）和θ（θ）中的每一个，这些亚基导致产生相当数量的受体亚型。每种亚型都表现出不同的药理学和生理学特性。但大多数GABAARs是由两个α亚基、两个β亚基和一个γ亚基组成的，它们以γ2β2α1β2α1的形式围绕中心逆时针排列。成熟受体具有由GABA神经递质门控并由多种不同药物调节的中央氯离子通道。GABA合成或释放的变化可能对正常的脑功能有显着影响。此外，药物的分子相互作用和药理作用极为复杂。这是由于受体的结构异质性，以及存在多个变构结合位点以及可以与之结合的多种配体。值得注意的是，GABA能系统的功能障碍有助于几种疾病的发展。因此，了解GABAA受体缺陷与CNS疾病之间的关系对发现疾病发病机制和药物开发具有重要影响。迄今为止，很少有评论详细讨论GABAA受体。因此，本文就GABAARs的结构、生理和药理学特性进行综述，并对GABAARs最常见的相关疾病进行阐述。
γ-Aminobutyric acid sub-type A receptors (GABAARs) are the most prominent inhibitory neurotransmitter receptors in the CNS. They are a family of ligand-gated ion channel with significant physiological and therapeutic implications. GABAARs are heteropentamers formed from a selection of 19 subunits: six α (alpha1-6), three β (beta1-3), three γ (gamma1-3), three ρ (rho1-3), and one each of the δ (delta), ε (epsilon), π (pi), and θ (theta) which result in the production of a considerable number of receptor isoforms. Each isoform exhibits distinct pharmacological and physiological properties. However, the majority of GABAARs are composed of two α subunits, two β subunits, and one γ subunit arranged as γ2β2α1β2α1 counterclockwise around the center. The mature receptor has a central chloride ion channel gated by GABA neurotransmitter and modulated by a variety of different drugs. Changes in GABA synthesis or release may have a significant effect on normal brain function. Furthermore, The molecular interactions and pharmacological effects caused by drugs are extremely complex. This is due to the structural heterogeneity of the receptors, and the existence of multiple allosteric binding sites as well as a wide range of ligands that can bind to them. Notably, dysfunction of the GABAergic system contributes to the development of several diseases. Therefore, understanding the relationship between GABAA receptor deficits and CNS disorders thus has a significant impact on the discovery of disease pathogenesis and drug development. To date, few reviews have discussed GABAA receptors in detail. Accordingly, this review aims to summarize the current understanding of the structural, physiological, and pharmacological properties of GABAARs, as well as shedding light on the most common associated disorders.
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影响因子：
7.6
作者：
Bloss, Cinnamon S.;Berrettini, Wade;Kaye, Walter H.
通讯作者：
Kaye, Walter H.
DOI：
10.1073/pnas.1424958112
发表时间：
2015-03-17
影响因子：
11.1
作者：
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影响因子：
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作者：
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通讯作者：
Wafford, KA