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674th Meeting

Structure, function and regulation of the 5-hydroxytryptamine (serotonin) transporter

S. Horschitz, R. Hummerich, P. Schloss
Biochemical Society Transactions Nov 01, 2001, 29 (6) 728-732; DOI: 10.1042/bst0290728
S. Horschitz
Central Institute of Mental Health, Biochemical Laboratory, J5, 68159 Mannheim, Germany
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  • For correspondence: shorsch@as200.zi-mannheim.de
R. Hummerich
Central Institute of Mental Health, Biochemical Laboratory, J5, 68159 Mannheim, Germany
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P. Schloss
Central Institute of Mental Health, Biochemical Laboratory, J5, 68159 Mannheim, Germany
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Abstract

The serotonin transporter (SERT), which terminates serotonergic neurotransmission by rapid reuptake of 5-hydroxytryptamine (5-HT) back into the nerve terminal was the subject of two studies. First, the regulatory effects of antidepressants on the expression of SERT was investigated. After chronic exposure of SERT to antidepressants, substrate transport and antidepressant binding parameters were determined. Long-term exposure of SERT to a selective 5-HT-re-uptake inhibitor, citalopram, resulted in the down-regulation of the expression level. The observed effects depend on drug concentration and exposure time and are reversible. Basal uptake levels could be regained 48 h after cessation of the treatment. Secondly, in order to gain insight into the molecular mechanism of substrate transport, potential interactions of SERT with the noradrenaline transporter (NET) have been investigated. A chimeric concatameric transporter construct consisting of rat SERT and rat NET has been cloned and characterized pharmacologically in a heterologous expression system.

  • noradrenaline
  • antidepressant uptake
  • 5-HT, 5-hydroxytryptamine
  • HEK-SERT, human embryonic kidney 293 cells that stably express the serotonin transporter
  • HEK-SmycN, SERT-myc-NET construct stably expressed in human embryonic kidney 293 cells
  • NE, norepinephrine (noradrenaline)
  • NET, norepinephrine transporter
  • PKC, protein kinase C
  • SERT, serotonin (5-hydroxytryptamine) transporter
  • SSRI, selective serotonin re-uptake inhibitor
  • © 2001 Biochemical Society
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November 2001

Volume: 29 Issue: 6

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Structure, function and regulation of the 5-hydroxytryptamine (serotonin) transporter
S. Horschitz, R. Hummerich, P. Schloss
Biochemical Society Transactions Nov 2001, 29 (6) 728-732; DOI: 10.1042/bst0290728
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Structure, function and regulation of the 5-hydroxytryptamine (serotonin) transporter
S. Horschitz, R. Hummerich, P. Schloss
Biochemical Society Transactions Nov 2001, 29 (6) 728-732; DOI: 10.1042/bst0290728

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Keywords

noradrenaline
antidepressant uptake
5-HT, 5-hydroxytryptamine
HEK-SERT, human embryonic kidney 293 cells that stably express the serotonin transporter
HEK-SmycN, SERT-myc-NET construct stably expressed in human embryonic kidney 293 cells
NE, norepinephrine (noradrenaline)
NET, norepinephrine transporter
PKC, protein kinase C
SERT, serotonin (5-hydroxytryptamine) transporter
SSRI, selective serotonin re-uptake inhibitor

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