单个丝氨酸残基控制大鼠血清素转运体底物转运的阳离子依赖性。
A single serine residue controls the cation dependence of substrate transport by the rat serotonin transporter.
作者信息
Sur C, Betz H, Schloss P
机构信息
Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse, 46, 60528 Frankfurt am Main, Germany.
出版信息
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7639-44. doi: 10.1073/pnas.94.14.7639.
Abstract
The serotonin transporter (SERT) is a member of the Na+/Cl--dependent neurotransmitter transporter family and constitutes the target of several clinically important antidepressants. Here, replacement of serine-545 in the recombinant rat SERT by alanine was found to alter the cation dependence of serotonin uptake. Substrate transport was now driven as efficiently by LiCl as by NaCl without significant changes in serotonin affinity. Binding of the antidepressant [3H]imipramine occurred with 1/5th the affinity, whereas [3H]citalopram binding was unchanged. These results indicate that serine-545 is a crucial determinant of both the cation dependence of serotonin transport by SERT and the imipramine binding properties of SERT.
摘要
血清素转运体（SERT）是Na⁺/Cl⁻依赖性神经递质转运体家族的成员，是几种临床上重要的抗抑郁药的作用靶点。在此，发现将重组大鼠SERT中的丝氨酸-545替换为丙氨酸会改变血清素摄取的阳离子依赖性。现在，LiCl驱动底物转运的效率与NaCl相同，而血清素亲和力无显著变化。抗抑郁药[³H]丙咪嗪的结合亲和力降低至原来的1/5，而[³H]西酞普兰的结合未改变。这些结果表明，丝氨酸-545是SERT转运血清素的阳离子依赖性和SERT丙咪嗪结合特性的关键决定因素。
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