抑制剂巴比妥酸盐和妊娠类固醇对GABAA受体的调节。

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Peters JA, Kirkness EF, Callachan H, Lambert JJ, Turner AJ

抑制剂巴比妥酸盐和妊娠类固醇对GABAA受体的调节。

中华药物学杂志1988年8月;94(4):1257-69。

PubMed ID

2850060 (PubMed视图

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摘要

1.孕酮和脱氧皮质酮的还原代谢物对γ -氨基丁酸(GABAA)受体的调节与抑制剂巴比妥酸盐产生的调节进行了比较:(a)细胞培养中酶分离的牛嗜铬酸细胞的电压钳记录，以及(b) [3H]-肌酚与猪脑膜制剂的特异性结合试验。2.孕酮代谢物5 α -和5 β -pregnan-3 α -ol-20-one(大于或等于30 nM)可逆且剂量依赖地增强了局部GABA (100 microM)引起的膜电流振幅，并且在30 nM-100 microM的浓度范围内刺激了[3H]-muscimol的结合。相比之下，5 α -和5 β -pregnan-3 β -ol-20-one (30 nM-100 microM)在两种试验中几乎没有影响，表明类固醇作用具有显著的立体选择性。3.对配体结合数据的Scatchard分析表明，作为活性类固醇异构体的主要作用，可检测的[3H]-muscimol结合位点的数量明显增加，而不是亲和力。4.雄酮(1微米)和脱氧皮质酮代谢物5 α -孕烯-3 α，21-二醇-20- 1 (100 nM)也增强了gaba诱发电流。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.

引用本文的药物库数据

药物靶点

药物	目标	种类	生物	药理作用	行动
司可巴比妥	γ -氨基丁酸受体亚基α -1	蛋白质	人类	是的	电位器	细节