Linked Life Data

11160629

Source:http://linkedlifedata.com/resource/pubmed/id/11160629

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-2-22
pubmed:abstractText
Although several model systems have been developed to characterize the function of the dopamine transporter (DAT), there is a relative lack of data regarding dopamine (DA) uptake by human caudate, as contrasted to binding studies. Cryopreserved human brain tissue can be used for functional as well as radioligand binding studies of neuronal proteins. The drug-induced inhibition of [125I]RTI-55 binding to, and [3H]DA uptake by, cryopreserved human caudate preparations has now been characterized. Using human caudate membranes, a single site for [125I]RTI-55 binding was observed in association and saturation experiments. The relative potencies of 22 drugs for inhibition of [125I]RTI-55 binding to membranes prepared from cryopreserved human caudate, fresh rat striatum, and HEK293 cells expressing the recombinant human DAT (HEK-hDAT) were highly correlated. The affinity of DA for the DAT, as measured by [3H]DA uptake experiments, was higher in both the cryopreserved human caudate and freshly prepared rat striatum than in HEK-hDAT cells. Although affinities were similar in rat and human brain tissue preparations, the maximal uptake rate in the cryopreserved human caudate was approximately 1 to 4% and 7% of the rate in fresh and cryopreserved rat striatal preparations, respectively. The relative potencies of 22 drugs for inhibition of [3H]DA uptake were similar for tissue prepared from cryopreserved human caudate, nonfrozen rat striatum, and intact HEK-hDAT cells. These data suggest that cryopreserved human caudate can be used to characterize drug interactions with the DAT, and that HEK-hDAT cells provide a comparable system for modeling the initial interaction of drugs with native hDAT.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
442-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11160629-Animals, pubmed-meshheading:11160629-Carrier Proteins, pubmed-meshheading:11160629-Caudate Nucleus, pubmed-meshheading:11160629-Cocaine, pubmed-meshheading:11160629-Cryopreservation, pubmed-meshheading:11160629-Dopamine, pubmed-meshheading:11160629-Dopamine Agonists, pubmed-meshheading:11160629-Dopamine Antagonists, pubmed-meshheading:11160629-Dopamine Plasma Membrane Transport Proteins, pubmed-meshheading:11160629-Humans, pubmed-meshheading:11160629-Kinetics, pubmed-meshheading:11160629-Male, pubmed-meshheading:11160629-Membrane Glycoproteins, pubmed-meshheading:11160629-Membrane Transport Proteins, pubmed-meshheading:11160629-Membranes, pubmed-meshheading:11160629-Nerve Tissue Proteins, pubmed-meshheading:11160629-Radioligand Assay, pubmed-meshheading:11160629-Rats, pubmed-meshheading:11160629-Rats, Sprague-Dawley, pubmed-meshheading:11160629-Synaptosomes
pubmed:year
2001
pubmed:articleTitle
Drug interactions with the dopamine transporter in cryopreserved human caudate.
pubmed:affiliation
Research Service, Veterans Affairs Medical Center, Portland, Oregon, 97201, USA. eshleman@ohsu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.