Cloning and expression of a functional serotonin transporter from rat brain.

Blakely RD, Berson HE, Fremeau RT, Caron MG, Peek MM, Prince HK, Bradley CC
Nature. 1991 354 (6348): 66-70

PMID: 1944572 · DOI:10.1038/354066a0

Selective antagonism of serotonin (5-hydroxytryptamine, 5HT) and noradrenaline transport by antidepressants is a key element in the 'amine' hypothesis of affective disorders. Uptake and/or transport sites of 5HT have been reported to be reduced in platelets of patients suffering from depression and in post-mortem brain samples of depressed patients and suicide victims. To date there has been little molecular information available on the structure and regulation of 5HT transporters. Using the polymerase chain reaction with degenerate oligonucleotides derived from two highly conserved regions of the transporters for noradrenaline and gamma-aminobutyric acid (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 nonneural cells, with transport selectively and potently antagonized by 5HT uptake-specific antidepressants, including paroxetine, citalopram and fluoxetine.

MeSH Terms (13)

Amino Acid Sequence Animals Base Sequence Brain Carrier Proteins Cloning, Molecular Molecular Sequence Data Oligonucleotides, Antisense Open Reading Frames Polymerase Chain Reaction Rats RNA, Messenger Serotonin

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