Flux coupling in the human serotonin transporter
Flux coupling in the human serotonin transporter
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DOI：
10.1016/s0006-3495(02)75328-9
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发表时间：
2002-12-01
影响因子：
3.4
通讯作者：
DeFelice, LJ
中科院分区：
文献类型：
--
作者：
Adams, SV;DeFelice, LJ
血清素（5-羟色胺；5HT）转运蛋白 (SERT) 催化 5HT 穿过细胞膜的运动。在大脑中，SERT 清除细胞外空间中的 5HT，调节血清素信号的强度和持续时间。 SERT 也是抗抑郁药和滥用药物的重要药理学靶点。我们研究了放射性标记的 5HT 通过 HEK-293 细胞中稳定表达的转运蛋白的通量。对净转运的时间过程、持续的平衡 5HT 梯度以及 5HT 单向流入与流出的比率的分析表明，从机制上讲，人类 SERT 充当 5HT 通道而不是经典载体。这在相对较高的[5HT](out)（大于或等于10μM）下尤其明显，但不限于外部5HT的这种状态。
The serotonin (5-hydroxytryptamine; 5HT) transporter (SERT) catalyzes the movement of 5HT across cellular membranes. In the brain, SERT clears 5HT from extracellular spaces, modulating the strength and duration of serotonergic signaling. SERT is also an important pharmacological target for antidepressants and drugs of abuse. We have studied the flux of radio-labeled 5HT through the transporter stably expressed in HEK-293 cells. Analysis of the time course of net transport, the equilibrium 5HT gradient sustained, and the ratio of the unidirectional influx to efflux of 5HT indicate that mechanistically, human SERT functions as a 5HT channel rather than a classical carrier. This is especially apparent at relatively high [5HT](out) (greater than or equal to10 muM), but is not restricted to this regime of external 5HT.