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| CLONING AND EXPRESSION OF A FUNCTIONAL SEROTONIN TRANSPORTER FROM RAT-BRAIN |
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| Author(s): BLAKELY RD, BERSON HE, FREMEAU RT, CARON MG, PEEK MM, PRINCE HK, BRADLEY CC |
| Source: NATURE Volume: 354 Issue: 6348 Pages: 66-70 Published: NOV 7 1991 |
| Times Cited: 575 References: 39 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: BLAKELY, RD (reprint author), EMORY UNIV, SCH MED, DEPT ANAT & CELL BIOL, ATLANTA, GA 30322 USA |
Addresses:
1. EMORY UNIV, SCH MED, PROGRAM NEUROSCI, ATLANTA, GA 30322 USA
2. DUKE UNIV, SCH MED, DEPT NEUROBIOL, DURHAM, NC 27710 USA
3. DUKE UNIV, SCH MED, DEPT CELL BIOL & MED, DURHAM, NC 27710 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: GN829 |
| ISSN: 0028-0836 |
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