Molecular, functional and biochemical characteristics of the dopamine transporter: Regional differences and clinical relevance

A. Hitri, Y. L. Hurd, R. J. Wyatt, S. I. Deutsch

Research output: Contribution to journalReview articlepeer-review

67 Scopus citations

Abstract

The carrier molecule that transports dopamine (DA) across the synaptic membrane is known as the dopamine transporter (DAT). Depending on the ionic conditions, DAT may function as a mediator of both the inward directed DA transport known as the 'reuptake' and the outward directed DA transport known as the 'release.' The functional significance of DAT is in the regulation of DA neurotransmission by terminating the action of DA in the synapse via reuptake. With use of DAT binding as a presynaptic marker to measure altered DA innervation, abnormalities of the DAT binding have been demonstrated in idiopathic Parkinson's disease, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity, and progressive supranuclear palsy. Moreover, the identification of DAT as the neuronal element that mediates the addictive properties of cocaine highlights its significance in cocaine addiction. Cocaine binding in the brain is heterogeneous, and there is an uneven distribution of the high- and low-affinity binding sites across the anatomical regions. Regional differences in ligand binding are observed by using both [3H]cocaine and the diphenyl-substituted piperazine derivatives known as the 'GBR series' of ligands. The identification of compounds that inhibit the binding of cocaine without affecting DA uptake could potentially lead to development of medications for cocaine abuse. Furthermore, clarification of the various binding domains that may be relevant to transporter function in human neuropsychiatric disorders may lead to the development of new medications for schizophrenia, Tourette's disease, and drug addiction.

Original languageEnglish
Pages (from-to)1-22
Number of pages22
JournalClinical Neuropharmacology
Volume17
Issue number1
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • Age
  • Cocaine
  • Dopamine transporter
  • Parkinson's disease
  • Schizophrenia
  • Tourette's disease
  • [H]GBR 12935

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