Nicotine stimulates transcriptional activity of the human dopamine transporter gene

K. Ohyama, Chiharu Sogawa, N. Sogawa, K. Morita, T. Dohi, S. Kitayama

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 languageEnglish
Pages (from-to)34-37
Number of pages4
JournalNeuroscience Letters
Volume471
Issue number1
DOIs
Publication statusPublished - Feb 26 2010

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Nicotine
Human Activities
Genes
Transcriptional Silencer Elements
Gene Expression
Hexamethonium
Transcription Initiation Site
COS Cells
Nicotinic Receptors
Cholinergic Antagonists
Luciferases
Genetic Promoter Regions
Introns
Cholinergic Agents
Up-Regulation
Central Nervous System
Cell Line

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 journalArticle

Ohyama, K. ; Sogawa, Chiharu ; Sogawa, N. ; Morita, K. ; Dohi, T. ; Kitayama, S. / Nicotine stimulates transcriptional activity of the human dopamine transporter gene. In: Neuroscience Letters. 2010 ; Vol. 471, No. 1. pp. 34-37.
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