Yu R, Ticku M K
Department of Pharmacology, University of Texas Health Science Center at San Antonio, USA.
J Pharmacol Exp Ther. 1995 Dec;275(3):1442-6.
In this study we examined the binding characteristics of the gamma-aminobutyric acid (GABAA) receptor complex after chronic pentobarbital sodium treatment in cultured mammalian cortical neurons. Chronic pentobarbital sodium treatment (200 microM, 5 days) did not alter the basal binding of ligands like [3H]flunitrazepam, [3H]ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5 alpha][1,4]-BZ-3-carboxylate and [3H]ethyl-8-azido-5,6-dihydro- 5-methyl-6-oxo-4H-imidazo [1,5 alpha][1,4]BZ-3-carboxylate that bind to the benzodiazepine (BZ) recognition site of the GABAA receptor complex. Similarly, chronic pentobarbital sodium treatment did not alter the basal binding of [3H]GABA and t-butylbicyclophosphoro[35S]thionate. However, chronic pentobarbital sodium treatment produced uncoupling between GABA, barbiturate and neurosteroid sites with the BZ site. The efficacy (Emax) values of GABA, pentobarbital and neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one, on [3H]flunitrazepam binding were significantly decreased, whereas their potency (EC50) values were not altered after chronic pentobarbital sodium treatment. Taken together, these results suggest that chronic pentobarbital sodium treatment produces heterologous uncoupling of the GABA-BZ receptor ionophore complex.
在本研究中，我们检测了在培养的哺乳动物皮层神经元中，慢性戊巴比妥钠处理后γ-氨基丁酸（GABAA）受体复合物的结合特性。慢性戊巴比妥钠处理（200微摩尔，5天）并未改变诸如[3H]氟硝西泮、[3H]乙基-8-氟-5,6-二氢-5-甲基-6-氧代-4H-咪唑并[1,5α][1,4]-BZ-3-羧酸盐和[3H]乙基-8-叠氮基-5,6-二氢-5-甲基-6-氧代-4H-咪唑并[1,5α][1,4]BZ-3-羧酸盐等与GABAA受体复合物的苯二氮䓬（BZ）识别位点结合的配体的基础结合。同样，慢性戊巴比妥钠处理也未改变[3H]GABA和叔丁基双环磷硫代[35S]酸盐的基础结合。然而，慢性戊巴比妥钠处理导致GABA、巴比妥酸盐和神经甾体位点与BZ位点之间发生解偶联。GABA、戊巴比妥和神经甾体5α-孕烷-3α-醇-20-酮对[3H]氟硝西泮结合的效能（Emax）值显著降低，而在慢性戊巴比妥钠处理后它们的效价（EC50）值未改变。综上所述，这些结果表明慢性戊巴比妥钠处理导致GABA-BZ受体离子通道复合物发生异源解偶联。
