Linked Life Data

21689106

Source:http://linkedlifedata.com/resource/pubmed/id/21689106

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-8-12
pubmed:abstractText
Dopamine (DA) is an important transmitter in both motor and limbic pathways. We sought to investigate the role of D(1)-receptor activation in axonal DA release regulation in dorsal striatum using a D(1)-receptor antagonist, SKF-83566. Evoked DA release was monitored in rat striatal slices using fast-scan cyclic voltammetry. SKF-83566 caused a concentration-dependent increase in peak single-pulse evoked extracellular DA concentration, with a maximum increase of ? 65% in 5 ?M SKF-83566. This was accompanied by a concentration-dependent increase in extracellular DA concentration clearance time. Both effects were occluded by nomifensine (1 ?M), a dopamine transporter (DAT) inhibitor, suggesting that SKF-83566 acted via the DAT. We tested this by examining [(3)H]DA uptake into LLc-PK cells expressing rat DAT, and confirmed that SKF-83566 is a competitive DAT inhibitor with an IC(50) of 5.7 ?M. Binding studies with [(3)H]CFT, a cocaine analog, showed even more potent action of SKF-83566 at the DAT cocaine binding site (IC(50) = 0.51 ?M). Thus, data obtained using SKF-83566 as a D(1) DA-receptor antagonist may be confounded by concurrent DAT inhibition. More positively, however, SKF-83566 might be a candidate to attenuate cocaine effects in vivo because of the greater potency of this drug at the cocaine versus DA binding site of the DAT.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1471-4159
pubmed:author
pubmed:copyrightInfo
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
pubmed:issnType
Electronic
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
714-20
pubmed:meshHeading
pubmed-meshheading:21689106-2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, pubmed-meshheading:21689106-Animals, pubmed-meshheading:21689106-Dopamine, pubmed-meshheading:21689106-Dopamine Antagonists, pubmed-meshheading:21689106-Dopamine Plasma Membrane Transport Proteins, pubmed-meshheading:21689106-Dopamine Uptake Inhibitors, pubmed-meshheading:21689106-Dose-Response Relationship, Drug, pubmed-meshheading:21689106-Drug Interactions, pubmed-meshheading:21689106-Electrochemistry, pubmed-meshheading:21689106-Male, pubmed-meshheading:21689106-Nomifensine, pubmed-meshheading:21689106-Prosencephalon, pubmed-meshheading:21689106-Protein Binding, pubmed-meshheading:21689106-Rats, pubmed-meshheading:21689106-Rats, Sprague-Dawley, pubmed-meshheading:21689106-Tritium, pubmed-meshheading:21689106-Tropanes
pubmed:year
2011
pubmed:articleTitle
SKF-83566, a D1-dopamine receptor antagonist, inhibits the dopamine transporter.
pubmed:affiliation
Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, N.I.H., Extramural