调制GABAA受体的抑制剂巴比妥酸盐和孕烷类固醇。

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彼得斯是的,Kirkness EF, Callachan H,兰伯特JJ,特纳AJ

调制GABAA受体的抑制剂巴比妥酸盐和孕烷类固醇。

Br J杂志。1988年8月,94 (4):1257 - 69。

PubMed ID

2850060 (在PubMed

]

文摘

1。的调制gamma-aminobutyric acidA (GABAA)受体减少孕酮和去氧皮质酮的代谢产物所产生的价格相比有镇静作用的巴比妥酸盐:(a)电压钳记录从牛保持酶的分离嗜铬细胞在细胞培养,和(b)的特定绑定的测定[3 h] -muscimol猪脑膜的制备。2。孕酮代谢物5α-和5 beta-pregnan-3 alpha-ol-20-one(大于或等于30 nM)可逆和剂量依赖性增强振幅膜电流引起的局部应用GABA (100 microM)和浓度范围30 nM - 100 microM刺激[3 h] -muscimol的绑定。相比之下,5α-和5 beta-pregnan-3 beta-ol-20-one (30 nm - 100 microM)几乎没有效果分析,表明类固醇行动的立体选择性。3所示。Scatchard配体结合的分析数据表明一个数量显著增加,而不是亲和力,可检测[3 h] -muscimol结合位点的原则行动活跃类固醇同分异构体。4所示。GABA-evoked电流也会使雄甾酮(1 microM)和去氧皮质酮代谢物5 alpha-pregnane-3α,21-diol-20-one(100海里)。5。 Secobarbitone (10-100 microM), pentobarbitone (10-300 microM) and phenobarbitone (100-500 microM) reversibly and dose-dependently potentiated the amplitude of GABA-evoked currents in the absence of any change in their reversal potential. 6. At relatively high concentrations (greater than or equal to 30 microM) secobarbitone and pentobarbitone directly elicited a membrane current. It is concluded that such currents result from GABAA receptor-channel activation since they share a common reversal potential with GABA-evoked responses (approximately 0 mV), are reversibly antagonized by bicuculline (3 microM), and potentiated by either diazepam (1 microM) or 5 beta-pregnan-3 alpha-ol-20-one (500 nM). 7. Secobarbitone (1 microM-1 mM) dose-dependently enhanced the binding of [3H]-muscimol. In common with the active steroids, an increase in the apparent number of binding sites was responsible for this effect. 8. A saturating concentration (1 mM) of secobarbitone in the ligand binding assay did not suppress the degree of enhancement of control binding produced by 5 beta-pregnan-3 alpha-ol-20-one (30 nM-100 microM). Similarly the steroid, at a concentration of 100 microM, did not influence the enhancement of [3H]-muscimol binding by secobarbitone (1 microM-1 mM). In all combinations of concentrations tested, the effects of secobarbitone and 5#-pregnan-3a-ol-20-one on [3H]-muscimol binding were additive. 9. In conjunction with previously published observations, the present data indicate close similarities in the GABA-mimetic and potentiating actions of barbiturates and steroids. However, the results obtained with combinations of steroids and barbiturates in the ligand binding assay appear inconsistent with the two classes of compound interacting with a common site to modulate the GABAA receptor activity.

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药物靶点

药物	目标	类	生物	药理作用	行动
司可巴比妥	γ-氨基丁酸受体亚基alpha -	蛋白质	人类	是的	电位器	细节