洛贝林抑制细胞膜多巴胺转运蛋白摄取  

Effects of lobeline on dopamine uptake by plasma membrane dopamine transporter

作　　者：栗超跃[1] 暨荀鹤[2] 惠国桢[3] 张建国[1] 周伟[1] 步星耀[1] 郭礼和[2] 

机构地区：[1]河南省人民医院神经外科,河南郑州450003 [2]中国科学院上海生命科学研究院生物化学与细胞生物学研究所基因工程组,上海210003 [3]苏州大学附一院神经外科,江苏苏州215006

出　　处：《中华神经外科疾病研究杂志》2007年第3期247-249,共3页Chinese Journal of Neurosurgical Disease Research

摘　　要：目的研究洛贝林调节多巴胺在细胞内外分布的作用位点及作用机制。方法利用六羟基多巴(6-OHDA)损伤偏侧部分多巴胺纹状体系统模型、Sprague-Dawley(SD)鼠纹状体突触体摄取实验和神经母细胞瘤细胞系(SK-N-SH)及永久转染细胞膜多巴胺转运蛋白的中国仓鼠卵巢细胞系(CHO)研究洛贝林作用位点及其机制。结果洛贝林可以有效降低6-OHDA损伤大鼠对阿朴吗啡的敏感性;洛贝林在细胞水平有效抑制多巴胺转运蛋白的转运活性,重新分布多巴胺在细胞内外浓度,而对多巴胺转运蛋白的释放功能没有影响。结论洛贝林通过有效抑制细胞膜多巴胺转运蛋白的摄取功能增加突触间隙内多巴胺浓度;洛贝林是多巴胺转运蛋白的有效抑制因子。Objective To explore the mechanism of lobeline on dopamine uptake by plasma membrane dopamine transporter. Methods 6-OHDA-induced hemiparkinsonism in medial forebrain bundle （MFB） was used to evaluate the effect of lobeline on nigraostriatal system from behavior in vivo; D8 cells and rat striatal synaptosomes were one model to study the effect of lobeline on DAT-mediated （ dopamine transporter protein, DAT） dopamine uptake and release. Results The results demonstrated that lobeline （3mg/kg） made a decrease in the emetomorphine-induced rotation rate and significantly inhibited 3H-dopamine uptake into D8 cells and tat striatal synaptosome~ in concentration- and time-dependent manner, but did not affect DAT-mediated release in D8 cells. Conclusion Lobeline is one inhibitor of DAT, which only inhibits dopamine uptake through DAT, but not affect DAT-mediated release.

关 键 词：洛贝林 多巴胺转运蛋白 抑制 

分 类 号：R730.246[医药卫生—肿瘤]