Regulation of dopamine and MPP + transport by catecholamine transporters

George R. Uhl, Toshihiro Dohi, Shigeo Kitayama, Norimitsu Morioka, Kei Kumagai, Chieko Mitsuhata, Katsuya Morita, Katsuyuki Kozai, Zhicheng Lin

Research output: Contribution to journalArticlepeer-review

Abstract

Following exocytotic release of the biogenic amine neurotransmitters, norepinephrine and dopamine, are removed from the synaptic cleft by the respective transporter, norepinephrine transporter (NET) and dopamine transporter (DAT) located on the plasma membrane. The catecholamine transporters are the molecular targets for psychoactive drugs as well as drugs of abuse such as cocaine and amphetamine and the Parkinsonism-inducing neurotoxin, MPP +. Nicotine regulates the transport of catecholamines and MPP + and may exert self-medicating effects for depression, schizophrenia and attention deficit hyperactivity disorder, and neuroprotective effects against MPP + through the regulation of the transporters. The availability of cDNAs of these transporters has permitted detailed pharmacological studies in heterologous expression systems for determining the mechanisms of action of nicotine on transporters. Moreover, functional analysis of the effect of single amino acid substitution suggests that specific residues in DAT molecules may play a significant role in interaction with MPP + and cocaine, and thus would promise a development of novel drugs with diverse chemical structures.

Original languageEnglish (US)
Pages (from-to)43-47
Number of pages5
JournalJapanese Journal of Neuropsychopharmacology
Volume24
Issue number2
StatePublished - Apr 2004
Externally publishedYes

Keywords

  • Cocaine
  • Dopamine transporter
  • MPP
  • Nicotine
  • Norepinephrine transporter

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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