Muscimol is a psychoactive isoxazole derived from the mushroom Amanita muscaria, and a potent orthosteric agonist of the GABA_A receptor. The binding of [³H]muscimol has been used to evaluate the distribution of GABA_A receptors in the brain, and studies of modulation of [³H]muscimol binding by allosteric GABAergic modulators such as barbiturates and steroid anesthetics have provided insight into the modes of action of these drugs on the GABA_A receptor. It has, however, not been feasible to directly apply interaction parameters derived from functional studies to describe the binding of muscimol to the receptor. Here, we employed the Monod-Wyman-Changeux concerted transition model to analyze muscimol binding isotherms. We show that the binding isotherms from recombinant α1β3 GABA_A receptors can be qualitatively predicted using electrophysiological data pertaining to properties of receptor activation and desensitization in the presence of muscimol. The model predicts enhancement of [³H]muscimol binding in the presence of the steroids allopregnanolone and pregnenolone sulfate, although the steroids interact with distinct sites and either enhance (allopregnanolone) or reduce (pregnenolone sulfate) receptor function. We infer that the concerted transition model can be used to link radioligand binding and electrophysiological data.

中文翻译：

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GABAA 受体变构调节剂增强蕈醇结合和门控：将占用与状态功能联系起来。


Muscimol 是一种从蘑菇伞菌中提取的精神活性异恶唑，也是 GABA _A受体的有效正构激动剂。 [ ³ H]蕈醇的结合已用于评估 GABA _A受体在大脑中的分布，并且通过变构 GABA 能调节剂（例如巴比妥类和类固醇麻醉剂）对 [ ³ H]蕈醇结合的调节研究提供了对该模式的深入了解这些药物对 GABA _A受体的作用。然而，直接应用源自功能研究的相互作用参数来描述蝇蕈醇与受体的结合还不可行。在这里，我们采用 Monod-Wyman-Changeux 协同转变模型来分析蝇蕈醇结合等温线。我们表明，可以使用与存在蝇蕈醇时受体激活和脱敏特性有关的电生理学数据来定性预测重组α1β3 GABA _A受体的结合等温线。该模型预测，在类固醇四氢孕酮和硫酸孕烯醇酮存在下，[ ³ H]蕈醇结合增强，尽管类固醇与不同位点相互作用并增强（四氢孕烯醇酮）或降低（硫酸孕烯醇酮）受体功能。我们推断协同转变模型可用于连接放射性配体结合和电生理学数据。