Pharmacological characterization of the cloned human 5-hydroxytryptamine transporter

We performed an extensive pharmacological study of the 5-hydroxytryptamine (5-HT) transporter polypeptide cloned from human placenta. Transient expression of this 630 amino acid polypeptide in HeLa cells led to saturable 5-HT uptake activity ( K m = 858 nM). This 5-HT uptake was blocked by selective...

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Bibliographic Details
Published in:Biochemical pharmacology 1996-05, Vol.51 (9), p.1145-1151
Main Authors: Agnel, Magali, Esnaud, Huguette, Langer, Salomon Z., Graham, David
Format: Article
Language:English
Subjects:
5-hydroxytryptamine transporter
[ 3H]5-HT uptake
[ 3H]citalopram binding
Antidepressive Agents, Tricyclic - pharmacology
Binding, Competitive
Biological and medical sciences
Carrier Proteins - drug effects
Carrier Proteins - genetics
Carrier Proteins - metabolism
Citalopram - metabolism
Cloning, Molecular
DNA, Complementary
fluoxetine
HeLa Cells
human placenta
Humans
Medical sciences
Membrane Glycoproteins - drug effects
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Membrane Transport Proteins
Nerve Tissue Proteins
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Radioligand Assay
Recombinant Proteins - drug effects
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Serotonin - metabolism
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors - pharmacology
Serotoninergic system
transfection
Tritium
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Summary:We performed an extensive pharmacological study of the 5-hydroxytryptamine (5-HT) transporter polypeptide cloned from human placenta. Transient expression of this 630 amino acid polypeptide in HeLa cells led to saturable 5-HT uptake activity ( K m = 858 nM). This 5-HT uptake was blocked by selective 5-HT inhibitors, such as citalopram, litoxetine, sertraline, and indalpine, with K i values in the low nanomolar range, and it exhibited a pharmacological profile similar to that found in rat brain. [ 3H]Citalopram binding to membrane preparations of the transfected cells occurred to a single class of high-affinity binding sites ( K d = 5.3 nM) and was potently inhibited by selective 5-HT uptake inhibitors. The pharmacological profile of [ 3H]citalopram binding to these transfected cells showed a good correlation with that of [ 3H]paroxetine binding to the rat cerebral cortical 5-HT transporter ( r = 0.79). These data confirm that the full pharmacological characteristics of the 5-HT transport system are conferred by the expression of the 630 amino acid human placental 5-HT transporter polypeptide. [ 3H]Citalopram should, therefore, provide a useful probe for more insights at a molecular level into this cloned 5-HT transport system.
ISSN:0006-2952
1873-2968
DOI:10.1016/0006-2952(96)00028-7