Linked Life Data

16510483

Source:http://linkedlifedata.com/resource/pubmed/id/16510483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-3-2
pubmed:abstractText
There is much evidence from animal studies that the recreational drug MDMA is a selective toxin which damages serotonin nerve terminals and axons. These in vivo studies show that an interaction between MDMA and the serotonin transporter protein (SERT) is the .rst step in toxicity. To further our understanding of the biochemical processes of MDMA toxicity we wished to use an in vitro model for toxicity. We produced two COS-7 cell lines with different levels of expression of recombinant rat SERT, as determined by 5-HT uptake assays, and compared them to human SERT expressing JAR cells and to untransfected COS-7 cells which do not express SERT. Cultured cells were exposed to MDMA (0.1 microM-1 mM) for 24 or 48 h at 37 degrees C before assessing cytotoxicity by LDH release and MTT turnover. Only at the highest concentration used, 1 mM, was MDMA cytotoxic, and this toxicity was found in all cell lines. Cytotoxicity caused by 48 h exposure to 1 mM MDMA at 37 degrees C was not related to the level of SERT expression, not blocked by the SERT-blocking drugs paroxetine or fluoxetine and not enhanced, in JAR cells, by forskolin preincubation that increased 5-HT uptake capacity by 50%. We conclude that SERT expression is not sufficient to confer MDMA toxicity to cell lines. Therefore SERT-expressing cell lines do not offer a simple model system to elucidate the mechanisms underlying MDMA toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0269-8811
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
257-63
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Serotonin transporter expression is not sufficient to confer cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in vitro.
pubmed:affiliation
Laboratory of Molecular Signalling, The Babraham Institute, Cambridge, UK.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't