Understanding the GABAA receptor: a chemically gated ion channel.
Understanding the GABAA receptor: a chemically gated ion channel.
复制标题
了解 GABAA 受体：化学门控离子通道。
作者：
F A Stephenson
γ-氨基丁酸（GABA）是哺乳动物中枢神经系统中主要的抑制性神经递质。 GABA 的主要作用是与特定受体蛋白相互作用，导致突触后膜的氯离子电导增加，从而抑制神经元放电。近年来，这种特殊受体——GABAA受体受到了广泛的关注，其原因有两个。首先，受体的药理学极其丰富，并且已知在同一受体寡聚物中至少存在三个相互作用的变构药物结合位点。这些包括镇静剂药物、苯二氮卓类药物和中枢神经系统抑制剂巴比妥类药物作用部位的药物。其次，也是独特的，相反的药理作用似乎是通过这种受体蛋白介导的。因此，在苯二氮卓位点相互作用的化合物可以具有抗焦虑作用，例如常用的安定，或者相反，它们可以具有引起焦虑和惊厥的特性；这种现象导致了“反向激动剂”这一非正统概念的产生（Haefely & Polc，1986）。本综述的目的是提出基于生化研究的 GABAA 受体分子结构的最新观点。还包括该领域令人兴奋的新进展，表明作为配体门控离子通道的神经递质受体蛋白，即烟碱乙酰胆碱受体、GABAA受体、甘氨酸受体以及可能的兴奋性氨基酸受体，属于化学门控离子通道超家族。
y-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system. The predominant effect of GABA is the interaction with a specific receptor protein which results in an increase of the chloride ion conductance of the post-synaptic membrane to produce an inhibition of neuronal firing. In recent years, much attention has been focused on this specific receptor, the GABAA receptor, and the reasons for this are two-fold. Firstly, the pharmacology of the receptor is extremely rich and a minimum of three interacting allosteric drug binding sites are known to occur within the same receptor oligomer. These include those for the site of action of the tranquillizer drugs, the benzodiazepines, and the central nervous system depressant barbiturates. Secondly, and uniquely, opposing pharmacological actions appear to be mediated through this one receptor protein. Thus compounds which interact at the benzodiazepine site can be anxiolytic, as exemplified by the often-prescribed valium, or conversely they can have anxiogenic and convulsant properties; this phenomenon has led to the unorthodox concept of the 'inverse agonist' (Haefely & Polc, 1986). The purpose of this review is to present current views on the molecular structure of the GABAA receptor, as derived from biochemical investigations. Included also will be an exciting new development in this field, the indication that the neurotransmitter receptor proteins that are ligand-gated ion channels, that is the nicotinic acetylcholine receptor, the GABAA receptor, the glycine receptor and possibly the receptors for the excitatory amino acids, belong to a superfamily of chemically gated ion channels.