Ueha T, Kuriyama K
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Alcohol Alcohol. 1991;26(1):17-24.
Effect of addition in vitro of ethanol on the functions of the GABAA receptor complex was investigated using synaptic membrane preparation obtained from mouse brain. Ethanol (50-200 mM) had no significant effect on the specific bindings of [3H]muscimol to GABAA receptor and [3H]flunitrazepam to benzodiazepine receptor in cerebral particulate preparations. However, ethanol induced an inhibition of [3H]TBOB binding to Cl- channel and a suppression of flunitrazepam-induced enhancement of [3H]muscimol binding and of salsolinol-induced accentuation of [3H]flunitrazepam binding to cerebral particulate fraction. In contrast, ethanol facilitated GABA-dependent 36Cl- influx but eliminated the stimulatory effects of flunitrazepam and salsolinol on GABA-dependent 36Cl- influx into cerebral membrane vesicles. These results suggest that ethanol may facilitate the function of GABA-gated chloride channel in spite of inducing deteriorations of antagonist binding capacity of chloride channel as well as of the functional coupling between GABAA receptor and benzodiazepine receptor in the brain.
利用从小鼠脑制备的突触膜，研究了体外添加乙醇对GABAA受体复合物功能的影响。乙醇（50 - 200 mM）对脑微粒体制剂中[3H]蝇蕈醇与GABAA受体的特异性结合以及[3H]氟硝西泮与苯二氮䓬受体的特异性结合均无显著影响。然而，乙醇可抑制[3H]TBOB与氯离子通道的结合，并抑制氟硝西泮诱导的[3H]蝇蕈醇结合增强以及鼠尾草碱诱导的[3H]氟硝西泮与脑微粒部分结合的增强。相反，乙醇促进了GABA依赖的36Cl-内流，但消除了氟硝西泮和鼠尾草碱对GABA依赖的36Cl-流入脑膜囊泡的刺激作用。这些结果表明，尽管乙醇会导致脑内氯离子通道拮抗剂结合能力以及GABAA受体与苯二氮䓬受体之间功能偶联的恶化，但它可能会促进GABA门控氯离子通道的功能。
