Debler E A, Hashim A, Lajtha A, Sershen H
Nathan S. Kline Institute for Psychiatric Research, Center for Neurochemistry, Ward's Island, New York, NY 10035.
Life Sci. 1988;42(25):2553-9. doi: 10.1016/0024-3205(88)90323-2.
The inhibition of uptake of [3H] dopamine and [3H] 1-methyl-4-phenylpyridine (MPP+) was examined in mouse striatal synaptosomal preparations. Kinetic analysis indicated that ascorbic acid is a noncompetitive inhibitor of [3H] MPP+ uptake. No inhibition of [3H] dopamine uptake is observed. The dopamine uptake blockers, GBR-12909, cocaine, and mazindol strongly inhibit (IC50 less than 1 uM) both [3H] dopamine and [3H] MPP+ transport. Nicotine, its metabolites, and other tobacco alkaloids are weak inhibitors (IC50 greater than 1 mM) except 4-phenylpyridine and lobeline, which are moderate inhibitors (IC50 = 3 to 40 uM) of both [3H] dopamine and [3H] MPP+ uptake. These similarities in potencies are in agreement with the suggestion that [3H] MPP+ and [3H] dopamine are transported by the same carrier. The differences observed in the alteration of dopaminergic transport and mazindol binding by ascorbic acid suggest that ascorbic acid's effects on [3H] MPP+ transport are related to translocation and/or dissociation processes occurring subsequent to the initial binding event.
在小鼠纹状体突触体标本中检测了[3H]多巴胺和[3H] 1-甲基-4-苯基吡啶（MPP+）摄取的抑制情况。动力学分析表明，抗坏血酸是[3H] MPP+摄取的非竞争性抑制剂。未观察到对[3H]多巴胺摄取的抑制作用。多巴胺摄取阻滞剂GBR-12909、可卡因和吗茚酮强烈抑制（IC50小于1 μM）[3H]多巴胺和[3H] MPP+的转运。尼古丁及其代谢产物以及其他烟草生物碱是弱抑制剂（IC50大于1 mM），但4-苯基吡啶和洛贝林除外，它们是[3H]多巴胺和[3H] MPP+摄取的中度抑制剂（IC50 = 3至40 μM）。这些效能上的相似性与[3H] MPP+和[3H]多巴胺由同一载体转运的观点一致。抗坏血酸在多巴胺能转运改变和吗茚酮结合方面观察到的差异表明，抗坏血酸对[3H] MPP+转运的影响与初始结合事件后发生的易位和/或解离过程有关。
