The ρ1 GABA_A receptor is prominently expressed in the retina and is present at lower levels in several brain regions and other tissues. Although the ρ1 receptor is insensitive to many anesthetic drugs that modulate the heteromeric GABA_A receptor, it maintains a rich and multifaceted steroid pharmacology. The receptor is negatively modulated by 5β-reduced steroids, sulfated or carboxylated steroids, and β-estradiol, whereas many 5α-reduced steroids potentiate the receptor. In this study, we analyzed modulation of the human ρ1 GABA_A receptor by several neurosteroids, individually and in combination, in the framework of the coagonist concerted transition model. Experiments involving coapplication of two or more steroids revealed that the receptor contains at least three classes of distinct, nonoverlapping sites for steroids, one each for the inhibitory steroids pregnanolone (3α5βP), 3α5βP sulfate, and β-estradiol. The site for 3α5βP can accommodate the potentiating steroid 5αTHDOC. The findings are discussed with respect to receptor modulation by combinations of endogenous neurosteroids.

中文翻译：

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通过抑制性和增强性神经类固醇的组合对 ρ1 GABAA 受体的调节分析揭示了共享和不同的结合位点。

的ρ 1 GABA_甲受体在视网膜中显着表达和存在于较低水平在几个脑区域和其他组织。尽管ρ 1 受体对许多调节异聚 GABA _A受体的麻醉药物不敏感，但它保持着丰富和多方面的类固醇药理学。该受体受到 5 β-还原类固醇、硫酸化或羧化类固醇和β-雌二醇的负调节，而许多 5 α-还原类固醇增强受体。在这项研究中，我们分析了人类ρ 1 GABA _{A 的}调制在协同剂协调转换模型的框架内，通过几种神经类固醇单独和组合地调节受体。涉及两个或更多的类固醇coapplication实验表明，该受体包含至少三类不同的，非重叠位点的类固醇，分别用于抑制类固醇孕（3 α 5 β P），3 α 5 β P硫酸盐，和β -雌二醇。3 α 5 β P 的位置可以容纳增强类固醇 5αTHDOC。就通过内源性神经类固醇的组合进行的受体调节来讨论这些发现。