STEROID-HORMONE METABOLITES ARE BARBITURATE-LIKE MODULATORS OF THE GABA RECEPTOR
STEROID-HORMONE METABOLITES ARE BARBITURATE-LIKE MODULATORS OF THE GABA RECEPTOR
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DOI：
10.1126/science.2422758
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发表时间：
1986-05-23
期刊：
影响因子：
56.9
通讯作者：
PAUL, SM
中科院分区：
文献类型：
--
作者：
MAJEWSKA, MD;HARRISON, NL;PAUL, SM
类固醇激素孕酮和脱氧皮质酮的两种代谢物，3α-羟基-5-α-二氢孕酮和3α，5α-四氢脱氧皮质酮，是γ-氨基丁酸(GABA)受体-氯离子通道复合物的有效巴比妥类配体。当浓度在 10-7 和 10-5M 之间时，两种类固醇都会抑制惊厥药叔丁基二环硫代磷酸酯与 GABA 受体复合物的结合，并增加苯二氮卓类药物氟硝西泮的结合。它们还刺激分离的脑囊泡吸收氯离子（通过吸收 36Cl- 来测量），并增强 GABA 在培养的大鼠海马和脊髓神经元中的抑制作用。这些数据可以解释某些类固醇激素快速改变神经元兴奋性的能力，并可以为天然存在和合成的麻醉类固醇的麻醉和催眠作用提供机制。
Two metabolites of the steroid hormones progresterone and deoxycorticosterone, 3.alpha.-hydroxy-5-.alpha.-dihydroprogesterone and 3.alpha.,5.alpha.-tetrahydrodeoxycorticosterone, are potent barbiturate-like ligands of the .gamma.-aminobutyric acid (GABA) receptor-chloride ion channel complex. At concentrations between 10-7 and 10-5M both steroids inhibited binding of the convulsant t-butylbicyclophosphorothionate to the GABA-receptor complex and increased the binding of the benzodiazepine flunitrazepam; they also stimulted chloride uptake (as measured by uptake of 36Cl-) into isolated brain vesicles, and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons. These data may explain the ability of certain steroid hormones to rapid alter neuronal excitability and may provide a mechanism for the anesthetic and hypnotic actions of naturally occurring and synthetic anesthetic steroids.