Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters.

Ecstasy samples often contain byproducts of the illegal, uncontrolled synthesis of N-methyl-3,4-methylenedioxy-amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). MDMA and eight chemically defined byproducts of MDMA synthesis were investigated for their interaction with the primary sites of action of MDMA, namely the human plasmalemmal monamine transporters for norepinephrine, serotonin, and dopamine [(norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT)]. SK-N-MC neuroblastoma and human embryonic kidney cells stably transfected with the transporter cDNA were used for uptake and release experiments.

Dopamine inhibits cell growth and cell cycle by blocking ribonucleotide reductase.

Dopamine (DA) is a classical neurotransmitter modulating various brain functions by acting on its specific receptors. In addition, DA is a reactive molecule that has been implicated in neurodegeneration, especially in Parkinson's disease. Here we show that DA inhibited cell growth of dopamine transporter transfected cells by intracellularly blocking cell cycle progression.

alpha-Synuclein selectively increases manganese-induced viability loss in SK-N-MC neuroblastoma cells expressing the human dopamine transporter.

The established or potentially toxic agents implicated in the nigral cell death in Parkinson's disease, dopamine, 1-methyl-4-phenylpyridinium (MPP(+)), iron, and manganese, were examined as to their effects on the viability of cells overexpressing alpha-synuclein. SK-N-MC neuroblastoma cells stably expressing the human dopamine transporter were transfected with human alpha-synuclein and cell clones with and without alpha-synuclein immunoreactivity were obtained. Cells were exposed for 24-72 h to 1-10 microM dopamine, 0.

Zn2+ modulates currents generated by the dopamine transporter: parallel effects on amphetamine-induced charge transfer and release.

The psychostimulant drug amphetamine increases extracellular monamines in the brain acting on neurotransmitter transporters, especially the dopamine transporter. Mediated by this plasmalemmal pump, amphetamine does not only induce release but also charge transfer which might be involved in the release mechanism. To study a potential link between the two phenomena, we used Zn(2+) as an acute regulatory agent which modulates dopamine uptake by a direct interaction with the transporter protein.

Cellular effects of dopamine--beyond oxidative mechanisms.

Cell cycle blockers inhibit growth in dividing cells, but promote survival of differentiated cells, including neurons. Low micromolar dopamine profoundly inhibited cell growth in dopamine transporter transfected SK-N-MC neuroblastoma cells by cell cycle arrest at G(1). This effect was independent of oxy radical formation, antagonized by transporter block, abolished by FeCl(3) and mimicked by the iron chelator deferoxamine.

Transporter-mediated release: a superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter.

HEK 293 cells stably expressing the human serotonin transporter (hSERT) were grown on coverslips, preincubated with [(3)H]5-hydroxytryptamine (5-HT), and superfused. Substrates of the hSERT [e.g.