Sulfatide and GM1 ganglioside modulate the high-affinity dopamine uptake in rat striatal synaptosomes: evidence for the involvement of their ionic charges
Sulfatide and GM1 ganglioside modulate the high-affinity dopamine uptake in rat striatal synaptosomes: evidence for the involvement of their ionic charges
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DOI：
10.1016/s0197-0186(02)00103-1
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发表时间：
2003-03-01
影响因子：
4.2
通讯作者：
Portoukalian, J
中科院分区：
文献类型：
--
作者：
Barrier, L;Page, G;Portoukalian, J
本研究观察了阴离子糖脂GM 1神经节苷脂和硫苷脂对大鼠纹状体突触体高亲和性多巴胺（DA）摄取的影响，结果表明，GM 1与突触体孵育1h后，可稳定结合于突触体，并改变神经元多巴胺转运体（DAT）的活性。在1.2和12 μ M GM 1时，Vmax分别降低了13%和23%，反映了功能性摄取位点数量的轻微减少，K-m降低了21%和33%，从而显示出亲和力的增加。用1.2 μ M的硫苷脂处理突触体，硫苷脂具有阴离子硫酸化基团，导致与GM 1相似的V-max降低（19%），但K-m降低显著更高（35%）。事实上，硫苷脂与突触体的结合程度是GM 1的3.5倍。相反，当GM 1和硫苷脂被GM 1酒精和半乳糖神经酰胺，分别取代时，没有修改的DA摄取发生，虽然这些中性糖脂纳入突触体的相关阴离子化合物在相同程度上，总之，这些结果表明连接到寡糖，糖脂链在调制DA跨突触体膜运输的负电荷的关键作用。(C)2002爱思唯尔科技有限公司。保留所有权利。
The present study was undertaken to examine the effects of the anionic glycolipids GM1 ganglioside and sulfatide on the high-affinity dopamine (DA) uptake in rat striatal synaptosomes.After 1 h of incubation, GM1 stably bound to synaptosomes and modified the activity of the neuronal dopamine transporter (DAT). With 1.2 and 12 muM GM1, V-max decreased by 13 and 23%, respectively, reflecting a slight reduction of the number of functional uptake sites and K-m was lowered by 21 and 33%, thus showing an increase of the affinity. Treatment of synaptosomes with 1.2 muM of sulfatide, which possesses an anionic sulfated group, led to a similar decrease of V-max (19%) than GM1, but to a significantly higher reduction of K-m (35%). In fact, sulfatide associated to synaptosomes in a 3.5-fold higher extent than GM1. Conversely, when GM1 and sulfatide were replaced by GM1 alcohol and galactosylceramide, respectively, no modification of the DA uptake occurred, although these neutral glycolipids incorporated into the synaptosomes to the same extent as the related anionic compounds.Altogether, these results demonstrate the key role of negative charges linked to the oligosaccharide, chains of glycolipids in the modulation of DA transport across the synaptosomal membrane. (C) 2002 Elsevier Science Ltd. All rights reserved.