In vitro studies of striatal vesicles containing the vesicular monoamine transporter (VMAT2): Rat versus mouse differences in sequestration of 1-methyl-4-phenylpyridinium

作     者：Staal, RGW Hogan, KA Liang, CL German, DC Sonsalla, PK 

作者机构：Univ Med & Dent New Jersey Robert Wood Johnson Med Sch Dept Neurol Piscataway NJ 08854 USA Univ Texas SW Med Ctr Dept Psychiat Dallas TX USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：2000年第293卷第2期

页      面：329-335页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：NIA NIH HHS [AG08479, AG08671] Funding Source: Medline NIEHS NIH HHS [ES07148] Funding Source: Medline 

主　　题：1-甲基-4-苯基吡啶/代谢 可卡因/类似物和衍生物 可卡因/代谢 多巴胺药/代谢 多巴胺摄取抑制剂/代谢 指示剂和试剂 动力学 膜糖蛋白类/代谢 膜转运蛋白质类 显微镜检查 电子 新纹状体/药物作用 新纹状体/代谢 新纹状体/超微结构 神经肽类 神经毒素类/代谢 神经递质药/代谢 大鼠 Sprague-Dawley 种特异性 突触小泡/药物作用 突触小泡/代谢 突触小泡/超微结构 囊泡生物胺转运蛋白质类 囊泡单胺转运蛋白质类 动物 男(雄)性 小鼠 大鼠 

摘      要：Significant differences exist in the sensitivity of mice and rats to the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that cannot be explained by differences in exposure to or uptake of 1-methyl-4-phenylpyridinium (MPP+) into dopamine (DA) neurons. MPP+ is also a substrate for the brain vesicular monoamine transporter (VMAT2), and sequestration into synaptic vesicles may be one mechanism of protection against MPP+ toxicity. A greater sequestration of MPP+ into vesicles of DA neurons in rats versus mice could explain the lower vulnerability of DA neurons in the rat to MPP+ toxicity. To test this hypothesis, the kinetics of uptake for [H-3]MPP+ and [H-3]DA as well as [H-3]dihydrotetrabenazine binding to VMAT2 were compared in vesicles isolated from the striata of rats and mice. The K-m value of [H-3]MPP+ transport was similar in the two species. In contrast, the maximal transport rate (V-max) was 2-fold greater in vesicles from rats than in those from mice. Likewise, the K-m value for [H-3]DA transport was similar in both preparations, but the V-max value was 2-fold greater in rat than in mouse vesicles. The B-max value for [H-3]dihydrotetrabenazine binding was also 2-fold greater in striatal vesicles from rats than in those from mice. Electron micrographs demonstrated that vesicles isolated from rats and mice were approximately the same size. Based on these observations, we propose that striatal vesicles from rats have more VMAT2 than vesicles from mice and that this species difference in VMAT2 density may help explain the reduced vulnerability of rat DA neurons to MPP+ neurotoxicity.