Serotonin-transporter mediated efflux: A pharmacological analysis of amphetamines and non-amphetamines
Serotonin-transporter mediated efflux: A pharmacological analysis of amphetamines and non-amphetamines
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DOI：
10.1016/j.neuropharm.2005.08.008
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发表时间：
2005-11-01
影响因子：
4.7
通讯作者：
Sitte, HH
中科院分区：
文献类型：
--
作者：
Hilber, B;Scholze, P;Sitte, HH
神经递质转运蛋白（如血清素转运蛋白（SERT））的生理功能是重摄取神经递质，终止突触胆碱能传递。SERT可以在相反方向上起作用，并由SERT底物诱导，包括5-HT、酪胺和带正电荷的甲基苯基吡啶（MPP+），以及苯丙胺衍生物对氯苯丙胺（pCA）和亚甲基二氧基甲基苯丙胺（MDMA）。这些底物还诱导主要由钠离子携带的内向钠电流。通过SERT的流出取决于这种钠通量，这被认为是向外运输的先决条件。然而，在最近的研究中，有人提出，底物可能是不同的属性，以诱导外排。因此，本研究的目的是在摄取实验中不同SERT底物的药理学表征，其诱导转运蛋白介导的外排和电流的能力。总之，在摄取和电生理学实验的亲和力的等级顺序相关性好，而安非他明衍生物的诱导外排的效力明显高于其他基板。这些差异只能用安非他明引起的机制来解释。因此，根据我们的药理学观察，我们得出结论，安非他明明显不同于非安非他明SERT底物。(c)2005爱思唯尔有限公司保留所有权利。
The physiological function of neurotransmitter transporter proteins like the serotonin transporter (SERT) is reuptake of neurotransmitter that terminates synaptic serotoninergic transmission. SERT can operate in reverse direction and be induced by SERT substrates including 5-HT, tyramine and the positively charged methyl-phenylpyridinium (MPP+), as well as the amphetamine derivatives para-chloroamphetamine (pCA) and methylene-dioxy-methamphetamine (MDMA). These substrates also induce inwardly directed sodium currents that are predominantly carried by sodium ions. Efflux via SERT depends on this sodium flux that is believed to be a prerequisite for outward transport. However, in recent studies, it has been suggested that substrates may be distinct in their properties to induce efflux. Therefore, the aim of the present study was a pharmacological characterization of different SERT substrates in uptake experiments, their abilities to induce transporter-mediated efflux and currents. In conclusion, the rank order of affinities in uptake and electrophysiological experiments correlate well, while the potencies of the amphetamine derivatives for the induction of efflux are clearly higher than those of the other substrates. These discrepancies can be only explained by mechanisms that can be induced by amphetamines. Therefore, based on our pharmacological observations, we conclude that amphetamines distinctly differ from non-amphetamine SERT substrates. (c) 2005 Elsevier Ltd. All rights reserved.