Abstract
Nicotine modulates dopaminergic activity in the central nervous system by acting on the reuptake system, including the dopamine transporter (DAT), although precisely remains unclear. Here we investigated the effect of nicotine on the transcriptional regulation of the human DAT (hDAT) gene by conducting luciferase reporter assays. Nicotine enhanced the transcription of hDAT gene constructs in transiently transfected SK-N-SH cells. Hexamethonium, a neuronal (ganglionic) nicotinic acetylcholine receptor antagonist, blocked the action of nicotine. Functional analyses placed the nicotine-responsive region -3.5 to -1.0 kb (from the transcription start site) upstream of the core promotor region. Deletion of intron 1, known as a silencer element of the hDAT gene, abolished nicotine's stimulatory effect. Nicotine failed to stimulate DAT promotor activity in non-neuronal CHO or COS-7 cells or in SK-N-AS cells, another neuronal cell line recently reported as a model for investigating DAT gene expression. These results suggest a nicotinic cholinergic mechanism to be involved in the nicotine-induced up-regulation of DAT gene expression.
| Original language | English |
|---|---|
| Pages (from-to) | 34-37 |
| Number of pages | 4 |
| Journal | Neuroscience Letters |
| Volume | 471 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Feb 26 2010 |
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Keywords
- Cholinergic receptor
- Dopamine
- Nicotine
- Transporter
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Nicotine stimulates transcriptional activity of the human dopamine transporter gene. / Ohyama, K.; Sogawa, Chiharu; Sogawa, N.; Morita, K.; Dohi, T.; Kitayama, S.
In: Neuroscience Letters, Vol. 471, No. 1, 26.02.2010, p. 34-37.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nicotine stimulates transcriptional activity of the human dopamine transporter gene
AU - Ohyama, K.
AU - Sogawa, Chiharu
AU - Sogawa, N.
AU - Morita, K.
AU - Dohi, T.
AU - Kitayama, S.
PY - 2010/2/26
Y1 - 2010/2/26
N2 - Nicotine modulates dopaminergic activity in the central nervous system by acting on the reuptake system, including the dopamine transporter (DAT), although precisely remains unclear. Here we investigated the effect of nicotine on the transcriptional regulation of the human DAT (hDAT) gene by conducting luciferase reporter assays. Nicotine enhanced the transcription of hDAT gene constructs in transiently transfected SK-N-SH cells. Hexamethonium, a neuronal (ganglionic) nicotinic acetylcholine receptor antagonist, blocked the action of nicotine. Functional analyses placed the nicotine-responsive region -3.5 to -1.0 kb (from the transcription start site) upstream of the core promotor region. Deletion of intron 1, known as a silencer element of the hDAT gene, abolished nicotine's stimulatory effect. Nicotine failed to stimulate DAT promotor activity in non-neuronal CHO or COS-7 cells or in SK-N-AS cells, another neuronal cell line recently reported as a model for investigating DAT gene expression. These results suggest a nicotinic cholinergic mechanism to be involved in the nicotine-induced up-regulation of DAT gene expression.
AB - Nicotine modulates dopaminergic activity in the central nervous system by acting on the reuptake system, including the dopamine transporter (DAT), although precisely remains unclear. Here we investigated the effect of nicotine on the transcriptional regulation of the human DAT (hDAT) gene by conducting luciferase reporter assays. Nicotine enhanced the transcription of hDAT gene constructs in transiently transfected SK-N-SH cells. Hexamethonium, a neuronal (ganglionic) nicotinic acetylcholine receptor antagonist, blocked the action of nicotine. Functional analyses placed the nicotine-responsive region -3.5 to -1.0 kb (from the transcription start site) upstream of the core promotor region. Deletion of intron 1, known as a silencer element of the hDAT gene, abolished nicotine's stimulatory effect. Nicotine failed to stimulate DAT promotor activity in non-neuronal CHO or COS-7 cells or in SK-N-AS cells, another neuronal cell line recently reported as a model for investigating DAT gene expression. These results suggest a nicotinic cholinergic mechanism to be involved in the nicotine-induced up-regulation of DAT gene expression.
KW - Cholinergic receptor
KW - Dopamine
KW - Nicotine
KW - Transporter
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U2 - 10.1016/j.neulet.2010.01.004
DO - 10.1016/j.neulet.2010.01.004
M3 - Article
C2 - 20074615
AN - SCOPUS:75749102650
VL - 471
SP - 34
EP - 37
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -