Ceramide-induced alterations in dopamine transporter function.
Ceramide-induced alterations in dopamine transporter function.
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DOI：
10.1016/s0014-2999(02)02727-9
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发表时间：
2003
影响因子：
5
通讯作者：
Evan L. Riddle;Kristi S. Rau;M. Topham;G. Hanson;A. Fleckenstein
中科院分区：
文献类型：
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作者：
Evan L. Riddle;Kristi S. Rau;M. Topham;G. Hanson;A. Fleckenstein
本研究的目的是确定神经酰胺对多巴胺和5-羟色胺（5-HT，5-羟色胺）转运体的影响。大鼠纹状体突触体暴露于C2-神经酰胺引起质膜多巴胺摄取可逆的，浓度依赖性的减少。相反，神经酰胺暴露增加纹状体5-HT突触体摄取。这种增加似乎不是由于5-HT转运蛋白的摄取增加。相反，这种增加似乎是由于通过多巴胺转运蛋白的5-HT转运增加所致，这一结论由以下发现证明：（1）不发生在海马突触体中（即，基本上不含多巴胺转运蛋白的制剂），（2）发生在从对氯苯丙胺处理的大鼠制备的纹状体突触体中（即，缺乏5-HT转运蛋白的制剂），（3）通过用哌甲酯预处理而减弱（即，相对选择性的多巴胺再摄取抑制剂）和（4）通过暴露于外源性多巴胺而被抑制（即，其可能与5-HT竞争摄取）。总之，这些结果表明，神经酰胺是一种新的单胺转运功能的调节剂，并可能改变多巴胺转运蛋白的亲和力，其主要底物。
The purpose of this study was to determine the effects of ceramide on dopamine and serotonin (5-HT, 5-hydroxytryptamine) transporters. Exposure of rat striatal synaptosomes to C2-ceramide caused a reversible, concentration-dependent decrease in plasmalemmal dopamine uptake. In contrast, ceramide exposure increased striatal 5-HT synaptosomal uptake. This increase did not appear to be due to an increased uptake by the 5-HT transporter. Rather, the increase appeared to result from an increase in 5-HT transport through the dopamine transporter, an assertion evidenced by findings that this increase: (1) does not occur in hippocampal synaptosomes (i.e., a preparation largely devoid of dopamine transporters), (2) occurs in striatal synaptosomes prepared from para-chloroamphetamine-treated rats (i.e., a preparation lacking 5-HT transporters), (3) is attenuated by pretreatment with methylphenidate (i.e., a relatively selective dopamine reuptake inhibitor) and (4) is inhibited by exposure to exogenous dopamine (i.e., which presumably competes for uptake with 5-HT). Taken together, these results reveal that ceramide is a novel modulator of monoamine transporter function, and may alter the affinity of dopamine transporters for its primary substrate.