Whatley V J, Brozowski S J, Hadingham K L, Whiting P J, Harris R A
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
J Neurochem. 1996 Mar;66(3):1318-21. doi: 10.1046/j.1471-4159.1996.66031318.x.
We studied whether microtubule organization is important for actions of ethanol on GABAA ergic responses by testing the effects of microtubule depolymerization on ethanol enhancement of GABA action in mouse L(tk-) cells stably transfected with GABAA receptor alpha 1 beta 1 gamma 2L subunits. The microtubule-disrupting agents colchicine, taxol, and vinblastine completely blocked ethanol-induced enhancement of muscimol-stimulated chloride uptake. beta-Lumicolchicine, a colchicine analogue that does not disrupt microtubules, had no effect on ethanol action. Colchicin did not alter the potentiating actions of flunitrazeparn or pentobarbital on muscimol-stimulated chloride uptakes. Thus, colchicine specifically inhibited the potentiating action of ethanol. From these findings, we conclude that intact microtubules are required for ethanol-induced enhancement of GABAA responses and suggest that a mechanism involving microtubules produces posttranslational modifications that are necessary for ethanol sensitivity in this cell system.
我们通过检测微管解聚对稳定转染GABAA受体α1β1γ2L亚基的小鼠L(tk-)细胞中乙醇增强GABA作用的影响，研究了微管组织对于乙醇作用于GABAA能反应是否重要。微管破坏剂秋水仙碱、紫杉醇和长春碱完全阻断了乙醇诱导的蝇蕈醇刺激的氯离子摄取增强。β-光秋水仙碱是一种不破坏微管的秋水仙碱类似物，对乙醇作用没有影响。秋水仙碱不改变氟硝西泮或戊巴比妥对蝇蕈醇刺激的氯离子摄取的增强作用。因此，秋水仙碱特异性抑制了乙醇的增强作用。从这些发现中，我们得出结论，完整的微管是乙醇诱导增强GABAA反应所必需的，并表明涉及微管的一种机制产生了翻译后修饰，而这种修饰是该细胞系统中乙醇敏感性所必需的。
