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Titolo:
MOLECULAR, FUNCTIONAL AND BIOCHEMICAL CHARACTERISTICS OF THE DOPAMINETRANSPORTER - REGIONAL DIFFERENCES AND CLINICAL RELEVANCE
Autore:
HITRI A; HURD YL; WYATT RJ; DEUTSCH SI;
Indirizzi:
DEPT VET AFFAIRS MED CTR,NIDA,RES UNIT,50 IRVING ST NW WASHINGTON DC 20422 DEPT VET AFFAIRS MED CTR,PSYCHIAT SERV WASHINGTON DC 00000 GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT WASHINGTON DC 20007 NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH WASHINGTON DC 20032 KAROLINSKA INST,DEPT PSYCHIAT & PSYCHOL S-10401 STOCKHOLM SWEDEN
Titolo Testata:
Clinical neuropharmacology
fascicolo: 1, volume: 17, anno: 1994,
pagine: 1 - 22
SICI:
0362-5664(1994)17:1<1:MFABCO>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; BRAIN GABA TRANSPORTER; COCAINE BINDING-SITES; H-3 GBR-12935 BINDING; RAT NUCLEUS-ACCUMBENS; PARKINSONS-DISEASE; )H-3>GBR-12935 BINDING; TOURETTE SYNDROME; NEURONAL UPTAKE; CHRONIC-SCHIZOPHRENIA;
Keywords:
DOPAMINE TRANSPORTER; COCAINE; [H-3] GBR 12935; AGE; PARKINSONS DISEASE; SCHIZOPHRENIA; TOURETTES DISEASE;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
141
Recensione:
Indirizzi per estratti:
Citazione:
A. Hitri et al., "MOLECULAR, FUNCTIONAL AND BIOCHEMICAL CHARACTERISTICS OF THE DOPAMINETRANSPORTER - REGIONAL DIFFERENCES AND CLINICAL RELEVANCE", Clinical neuropharmacology, 17(1), 1994, pp. 1-22

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 theaction 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 compoundsthat inhibit the binding of cocaine without affecting DA uptake couldpotentially 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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Documento generato il 04/04/20 alle ore 09:50:39