GABAA Receptors and the Diversity in their Structure and Pharmacology
GABAA Receptors and the Diversity in their Structure and Pharmacology
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DOI：
10.1016/bs.apha.2017.03.003
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Chebib, Mary
中科院分区：
文献类型：
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作者：
Chua, Han Chow;Chebib, Mary
GABA(A)受体（GABA(A)Rs）是一类具有高度生理和治疗意义的配体门控离子通道。在大脑中，这些五聚体受体以不同的亚基组成出现，这赋予了这类受体高度复杂的药理学。众所周知，临床使用的一系列治疗药物可以结合GABA(A)Rs上的不同位点来调节受体功能。多年来已经使用了许多实验方法来阐明这些药物的结合位点，但由于亚型和配体依赖的药理学，明确的鉴定是具有挑战性的。在这里，我们回顾了目前对GABAARs的结构和药理学理解，并强调了最近的证据，这些证据揭示了比以前预期的更大的复杂性。
GABA(A) receptors (GABA(A)Rs) are a class of ligand-gated ion channels with high physiological and therapeutic significance. In the brain, these pentameric receptors occur with diverse subunit composition, which confers highly complex pharmacology to this receptor class. An impressive range of clinically used therapeutics are known to bind to distinct sites found on GABA(A)Rs to modulate receptor function. Numerous experimental approaches have been used over the years to elucidate the binding sites of these drugs, but unequivocal identification is challenging due to subtype- and ligand-dependent pharmacology. Here, we review the current structural and pharmacological understanding of GABAARs, besides highlighting recent evidence which has revealed greater complexity than previously anticipated.