酒精对γ-氨基丁酸转运蛋白Ⅰ(GAT1)功能调节方式的初步研究  

ETHANOL AFFECTS THE FUNCTION OF γ-AMINOBUTYRIC ACID TRANSPORTER I IN MICE BRAIN

作　　者：姜杰[1] 胡佳华[2] 吴敏[1] 郭礼和[2] 费俭[2] 

机构地区：[1]浙江大学生命科学院,杭州310027 [2]中国科学院上海生命科学院生物化学与细胞生物学研究所,上海200031

出　　处：《实验生物学报》2004年第4期315-320,共6页Acta Biologiae Experimentalis Sinica

基　　金：国家自然科学基金资助(30370447)~~

摘　　要：已有报道GABA能系统参与酒精耐受和成瘾。我们实验室先前的研究表明急性和慢性酒精处理能快速增强小鼠中枢神经系统γ-氨基丁酸转运蛋白(GATs)的功能,但不影响中枢神经系统GAT1的基因表达水平;GABA 转运蛋白对底物的亲和性也未发生变化在本文中,我们用免疫荧光实验发现酒精处理后,GAT1蛋白向突触体质膜一侧聚集。蛋白磷酸化检测实验显示突触体内GAT1蛋白上丝氨酸、苏氨酸及酪氨酸的磷酸化水平降低。这些结果提示酒精通过刺激GAT1蛋白从胞内转位到突触质膜上而提高GABA 重摄取的功能,GAT1蛋白去磷酸化可能在此过程中发挥了重要作用。It has been suggested that GABAergie system was involved in ethanol toleranceand addiction.Our previous work indicated both acute and chronic ethanol treatment enhancedthe activity of GABA transporters in mouse brain.However,the expression level of CAT1 in CNSdoes not change,neither does the affinity of GABA transporters.In the present study,we demon-strated that CAT1 distribution on presynaptic membrane was altered after acute and chronicethanol administration.Furthermore,the phosphorylation levels of GAT1 on three sites includingSet,Tyr and Thr were decreased.These data suggested that ethanol enhanced the function ofGATs by means of inducing GAT1 redistribution in the cell and dephosphorylation may play arole in this process.

关 键 词：酒精 γ-氨基丁酸转运蛋白I 功能调节 转位 去磷酸化 GABA 中枢神经系统 神经递质 

分 类 号：R749.6[医药卫生—神经病学与精神病学]