PMID- 16510483
OWN - NLM
STAT- MEDLINE
DCOM- 20060809
LR  - 20191210
IS  - 0269-8811 (Print)
IS  - 0269-8811 (Linking)
VI  - 20
IP  - 2
DP  - 2006 Mar
TI  - Serotonin transporter expression is not sufficient to confer cytotoxicity to 
      3,4-methylenedioxymethamphetamine (MDMA) in vitro.
PG  - 257-63
AB  - 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.
FAU - Hayat, Shaista
AU  - Hayat S
AD  - Laboratory of Molecular Signalling, The Babraham Institute, Cambridge, UK.
FAU - Williams, Robert J
AU  - Williams RJ
FAU - Rattray, Marcus
AU  - Rattray M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Hallucinogens)
RN  - 0 (Malonates)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - 9KX7ZMG0MK (malonic acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Survival/*drug effects
MH  - Chlorocebus aethiops
MH  - Dopamine/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Hallucinogens/*toxicity
MH  - Malonates/*toxicity
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurons/drug effects
MH  - Rats
MH  - Serotonin/metabolism
MH  - Serotonin Agents/*toxicity
MH  - Serotonin Plasma Membrane Transport Proteins/*drug effects/genetics
MH  - Transfection
EDAT- 2006/03/03 09:00
MHDA- 2006/08/10 09:00
CRDT- 2006/03/03 09:00
PHST- 2006/03/03 09:00 [pubmed]
PHST- 2006/08/10 09:00 [medline]
PHST- 2006/03/03 09:00 [entrez]
AID - 20/2/257 [pii]
AID - 10.1177/0269881106063273 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2006 Mar;20(2):257-63. doi: 10.1177/0269881106063273.