Suzdak P D, Schwartz R D, Skolnick P, Paul S M
Proc Natl Acad Sci U S A. 1986 Jun;83(11):4071-5. doi: 10.1073/pnas.83.11.4071.
The effects of ethanol on Cl- uptake were studied using a cell-free subcellular preparation from brain that contains a gamma-aminobutyric acid (GABA)/barbiturate receptor-sensitive Cl- transport system. In isolated vesicles prepared from rat cerebral cortex, ethanol, at concentrations that are present during acute intoxication (20-50 mM), stimulated 36Cl- uptake in a concentration-dependent and biphasic manner. The ethanol-stimulated uptake of 36Cl- was markedly inhibited by the GABA antagonists picrotoxin and bicuculline but not by a variety of other neurotransmitter receptor antagonists. The effects of ethanol in stimulating 36Cl- uptake in isolated brain vesicles were qualitatively and quantitatively similar to that of pentobarbital. Ethanol also markedly potentiated both muscimol- and pentobarbital-stimulated 36Cl- uptake at concentrations below those that directly stimulate 36Cl- uptake. Under our incubation conditions, ethanol did not release GABA, suggesting that it interacts with the postsynaptic GABA/barbiturate receptor complex. The ability of ethanol to stimulate GABA/barbiturate receptor-mediated Cl- transport may explain many of its pharmacological properties and provides a mechanism for the common psychopharmacological actions of ethanol, barbiturates, and benzodiazepines.
利用含有γ-氨基丁酸（GABA）/巴比妥酸盐受体敏感性氯离子转运系统的无细胞脑亚细胞制剂，研究了乙醇对氯离子摄取的影响。在从大鼠大脑皮层制备的分离囊泡中，急性中毒时存在的浓度（20 - 50 mM）的乙醇以浓度依赖性和双相方式刺激36Cl-摄取。乙醇刺激的36Cl-摄取被GABA拮抗剂苦味毒和荷包牡丹碱显著抑制，但不被多种其他神经递质受体拮抗剂抑制。乙醇在分离的脑囊泡中刺激36Cl-摄取的作用在定性和定量上与戊巴比妥相似。在低于直接刺激36Cl-摄取的浓度下，乙醇还显著增强了蝇蕈醇和戊巴比妥刺激的36Cl-摄取。在我们的孵育条件下，乙醇不释放GABA，这表明它与突触后GABA/巴比妥酸盐受体复合物相互作用。乙醇刺激GABA/巴比妥酸盐受体介导的氯离子转运的能力可能解释了其许多药理特性，并为乙醇、巴比妥酸盐和苯二氮卓类药物常见的精神药理作用提供了一种机制。
