MOLECULAR, FUNCTIONAL AND BIOCHEMICAL CHARACTERISTICS OF THE DOPAMINE TRANSPORTER - REGIONAL DIFFERENCES AND CLINICAL RELEVANCE

被引:68
作者
HITRI, A
HURD, YL
WYATT, RJ
DEUTSCH, SI
机构
[1] DEPT VET AFFAIRS MED CTR, PSYCHIAT SERV, WASHINGTON, DC USA
[2] GEORGETOWN UNIV, SCH MED, DEPT PSYCHIAT, WASHINGTON, DC 20007 USA
[3] NIMH, CTR NEUROSCI, NEUROPSYCHIAT BRANCH, WASHINGTON, DC 20032 USA
[4] KAROLINSKA INST, DEPT PSYCHIAT & PSYCHOL, S-10401 STOCKHOLM, SWEDEN
关键词
DOPAMINE TRANSPORTER; COCAINE; H-3] GBR 12935; AGE; PARKINSONS DISEASE; SCHIZOPHRENIA; TOURETTES DISEASE;
D O I
10.1097/00002826-199402000-00001
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 [H-3]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.
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页码:1 / 22
页数:22
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