Olsen R W, Wong E H, Stauber G B, King R G
Fed Proc. 1984 Oct;43(13):2773-8.
The synaptic receptor sites for the neurotransmitter gamma-aminobutyric acid (GABA) can be assayed in vitro with several radiolabeled agonists and one antagonist. Numerous criteria of specificity have been met for these binding sites. All of the ligands show heterogeneity in binding affinities. The subpopulations thus defined have a remarkably similar specificity for GABA analogs, which suggests an intimate relationship and possible interconvertibility. Modulation of GABA receptor binding by barbiturates, anions, and other membrane treatments that affect agonists and antagonists in an opposite manner suggests a three-state model of interconvertible affinities. The complex of GABA receptor and chloride ion channel contains modulatory sites for barbiturates and benzodiazepines, drugs that enhance GABA responses in neurons. The receptor complex can be solubilized in detergent with the three mutually interacting receptor activities intact. The complex has an apparent molecular weight of 355,000 and has been partially purified. GABA agonist function has been assayed at the biochemical level by measuring the activation of 36Cl- efflux from preloaded hippocampal slices by GABA, muscimol, and barbiturates. This response is blocked by the antagonists of the GABA site (bicuculline) and the barbiturate site (picrotoxin). Comparison of binding and function on the same tissue should be useful in analyzing the mechanism of action of GABA.
神经递质γ-氨基丁酸（GABA）的突触受体位点可用几种放射性标记的激动剂和一种拮抗剂在体外进行测定。这些结合位点已满足众多特异性标准。所有配体在结合亲和力方面均表现出异质性。如此定义的亚群对GABA类似物具有非常相似的特异性，这表明它们之间存在密切关系且可能具有相互转换性。巴比妥类药物、阴离子以及其他以相反方式影响激动剂和拮抗剂的膜处理对GABA受体结合进行的调节表明存在一种亲和力可相互转换的三态模型。GABA受体与氯离子通道的复合物含有巴比妥类药物和苯二氮䓬类药物的调节位点，这些药物可增强神经元中的GABA反应。该受体复合物可用去污剂溶解，且三种相互作用的受体活性保持完整。该复合物的表观分子量为355,000，并且已得到部分纯化。通过测量GABA、蝇蕈醇和巴比妥类药物对预先加载的海马切片中36Cl-外流的激活，已在生化水平上测定了GABA激动剂的功能。这种反应被GABA位点拮抗剂（荷包牡丹碱）和巴比妥类药物位点拮抗剂（印防己毒素）阻断。在同一组织上比较结合与功能对于分析GABA的作用机制应该是有用的。
