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.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.