CLONING AND EXPRESSION OF A FUNCTIONAL SEROTONIN TRANSPORTER FROM RAT-BRAIN
CLONING AND EXPRESSION OF A FUNCTIONAL SEROTONIN TRANSPORTER FROM RAT-BRAIN
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DOI：
10.1038/354066a0
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发表时间：
1991-11-07
期刊：
影响因子：
64.8
通讯作者：
BRADLEY, CC
中科院分区：
文献类型：
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作者：
BLAKELY, RD;BERSON, HE;BRADLEY, CC
抗抑郁药对5-羟色胺（5-HT）和去甲肾上腺素转运的选择性拮抗作用是情感障碍“胺”假说的关键因素1。据报道，在患有抑郁症的患者的血小板中以及在抑郁症患者6和自杀受害者7的死后脑样品中，5 HT的摄取2、3和/或转运位点4-5减少。到目前为止，已经有很少的分子信息的结构和调节5 HT转运。使用聚合酶链反应8与简并寡核苷酸9来自两个高度保守的区域的转运去甲肾上腺素10和γ-氨基丁酸11（GABA），我们已经确定了一个大家族的相关基因产物在啮齿动物大脑中表达。其中一种产物与仅限于大鼠中脑和脑干的单个3.7-β-淀粉酶RNA杂交，在那里它高度富集在多巴胺能中缝复合体中。用单个2.3-腺苷酸酶脑干互补DNA克隆转染足以使Na+依赖性5 HT转运蛋白在非神经细胞上表达，其中转运蛋白被5 HT摄取特异性抗抑郁药（包括帕罗西汀、西酞普兰和氟西汀）选择性地和有效地拮抗。
SELECTIVE antagonism of serotonin (5-hydroxytryptamine, 5HT) and noradrenaline transport by antidepressants is a key element in the 'amine' hypothesis of affective disorders 1. Uptake 2,3 and/or transport sites 4-5 of 5HT have been reported to be reduced in platelets of patients suffering from depression and in post-mortem brain samples of depressed patients 6 and suicide victims 7. To date there has been little molecular information available on the structure and regulation of 5HT transporters. Using the polymerase chain reaction 8 with degenerate oligonucleotides 9 derived from two highly conserved regions of the transporters for noradrenaline 10 and gamma-aminobutyric acid 11 (GABA), we have identified a large family of related gene products expressed in rodent brain. One of these products hybridizes to a single 3.7-kilobase RNA restricted to rat midbrain and brainstem, where it is highly enriched within the serotonergic raphe complex. Transfection with a single 2.3-kilobase brainstem complementary DNA clone is sufficient to confer expression of a Na+-dependent 5HT transporter upon non-neural cells, with transport selectively and potently antagonized by 5HT uptake-specific antidepressants, including paroxetine, citalopram and fluoxetine.