Integrative transporter-mediated release from cytoplasmic and vesicular 5-hydroxytryptamine stores in cultured neurons.
The direct effects of 3,4-methylenedioxymethamphetamine (MDMA) and p-chloroamphetamine (PCA) were studied in microculture of fetal 5-hydroxytryptamine (5-HT) neurons. Both MDMA and PCA released 5-HT with the potency of PCA > MDMA by a mechanism inhibited by fluoxetine, and inhibitor of the 5-HT transporter. The transporter-mediated release by MDMA and PCA reduced intracellular stores of 5-HT. Both MDMA and PCA inhibit MAO-A activities, which also contributes to the increase of extracellular 5-HT levels. Deprenyl (10(-7) M) increased the amount of intracellular 5-HT and potentiated the MDMA- or PCA-induced release of 5-HT. Conversely, reserpine (10(-9) M) reduced the intracellular 5-HT levels and attenuated the transporter-mediated release. In addition, MDMA- or PCA-mediated release was attenuated by nimodipine (10(-8) M), an L-type Ca2+ channel antagonist. Our results indicate that MDMA- or PCA-induced release of 5-HT occurs from the cytoplasm to the media through the 5-HT transporter, and that the release may incorporate 5-HT from the vesicular stores.
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Department of Biology, New York University, NY 10003.
Azmitia
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D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003010:Clorgyline / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D005473:Fluoxetine; D012642:Selegiline; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D009553:Nimodipine; D010133:p-Chloroamphetamine; D012110:Reserpine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003010:Clorgyline