ANTIDEPRESSANT-SENSITIVE AND COCAINE-SENSITIVE HUMAN SEROTONIN TRANSPORTER - MOLECULAR-CLONING, EXPRESSION, AND CHROMOSOMAL LOCALIZATION
ANTIDEPRESSANT-SENSITIVE AND COCAINE-SENSITIVE HUMAN SEROTONIN TRANSPORTER - MOLECULAR-CLONING, EXPRESSION, AND CHROMOSOMAL LOCALIZATION
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DOI：
10.1073/pnas.90.6.2542
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发表时间：
1993-03-15
影响因子：
11.1
通讯作者：
BLAKELY, RD
中科院分区：
文献类型：
--
作者：
RAMAMOORTHY, S;BAUMAN, AL;BLAKELY, RD
5-羟色胺(5-羟色胺，5-羟色胺)转运蛋白是一种钠氯偶联的5-羟色胺转运体，表达于人的神经细胞、血小板、胎盘和肺膜上。大脑5-羟色胺转运体似乎是治疗抗抑郁药物的主要作用部位，并可能介导可卡因和苯丙胺的行为和/或毒性效应。来自共同转运体序列的寡核苷酸被用来鉴定与大鼠脑5HT载体高度相关的人胎盘cDNAs。将其中一个cDNA导入HeLa细胞产生高亲和力(K(M)=463nM)、依赖Na+和Cl-的5HT转运活性，该活性可被选择性的5HT转运抑制剂帕罗西汀、氟西汀和丙咪嗪所阻断，并被可卡因和苯丙胺所拮抗。序列分析显示，一个630个氨基酸的开放阅读框与克隆的大鼠脑内5HT转运蛋白具有92%的同源性，具有相同的预测拓扑特征和翻译后修饰的保守位点。与啮齿类动物不同，在啮齿类动物中，似乎只有一种mRNA编码5-羟色胺转运体，而在人类胎盘和肺中观察到多个杂交RNA。然而，体细胞杂交和原位杂交研究是一致的，编码人类5HT转运蛋白的单个基因定位于染色体17q11.1-17q12。
A Na+- and Cl--coupled serotonin (5-hydroxytryptamine, 5HT) transporter is expressed on human neuronal, platelet, placental, and pulmonary membranes. The brain 5HT transporter appears to be a principal site of action of therapeutic antidepressants and may mediate behavioral and/or toxic effects of cocaine and amphetamines. Oligonucleotides derived from consensus transporter sequences were used to identify human placental cDNAs highly related to the rat brain 5HT carrier. Transfection of one of these cDNAs into HeLa cells yields a high-affinity (K(m) = 463 nM), Na+- and Cl--dependent 5HT transport activity which can be blocked by selective 5HT transport inhibitors, including paroxetine, fluoxetine, and imipramine, and which is antagonized by cocaine and amphetamine. Sequence analysis reveals a 630-amino acid open reading frame bearing 92% identity to the cloned rat brain 5HT transporter, with identical predicted topological features and conserved sites for posttranslational modifications. Unlike the rodent, where a single mRNA appears to encode 5HT transporters, multiple hybridizing RNAs are observed in human placenta and lung. Somatic cell hybrid and in situ hybridization studies are consistent, however, with a single gene encoding the human 5HT transporter, localized to chromosome 17q11.1-17q12.