人类血清素转运体中的通量偶联
Flux coupling in the human serotonin transporter.
作者信息
Adams Scott V, DeFelice Louis J
机构信息
Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37232, USA.
出版信息
Biophys J. 2002 Dec;83(6):3268-82. doi: 10.1016/S0006-3495(02)75328-9.
Abstract
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 (> or =10 microM), but is not restricted to this regime of external 5HT.
摘要
血清素（5-羟色胺；5HT）转运体（SERT）催化5HT跨细胞膜的转运。在大脑中，SERT清除细胞外空间中的5HT，调节血清素能信号传导的强度和持续时间。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通过稳定表达于HEK-293细胞中的转运体的通量。对净转运的时间进程、维持的平衡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作为一个5HT通道发挥作用，而不是经典的载体。这在相对较高的细胞外5HT浓度（≥10 microM）时尤为明显，但并不局限于这种细胞外5HT浓度范围。
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