Temperature and 3,4-methylenedioxymethamphetamine alter human serotonin transporter-mediated dopamine uptake.
Although studies have suggested that dopamine can be transported by serotonin transporters (SERTs), such activity has not been characterized at the cloned SERTs. Dopamine and serotonin uptake by human SERT expressed in HEK-293 cells was compared at 37 and 40 degrees C. Elevated temperature was found to alter serotonin transport, but had no significant effect on dopamine transport. These effects led to a 10-fold increase in the serotonin:dopamine transport ratio reflecting an increased preference of SERTs for dopamine as opposed to serotonin at the higher temperature. The effects of 3,4-methylenedioxymethamphetamine (MDMA) on SERT-mediated dopamine transport were also evaluated by pre-incubating SERT-expressing cells with MDMA. The presence of intracellular MDMA caused a decrease in [3H]dopamine uptake but had no effect on [3H]serotonin transport suggesting that intracellular MDMA may be capable of inhibiting transporter function.
Saldaña
Shannon N
SN
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University School of Pharmacy, MCMP RHPH 202, 575 Stadium Mall Drive, West Lafayette, IN 47907-2091, USA.
Barker
Eric L
EL
D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D006801:Humans; D007668:Kidney; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D013696:Temperature; D014162:Transfection / Q000379:methods
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine