Integrative transporter-mediated release from cytoplasmic and vesicular 5-hydroxytryptamine stores in cultured neurons

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Abstract

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, an 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 level 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.

Original languageEnglish (US)
Pages (from-to)51-57
Number of pages7
JournalEuropean Journal of Pharmacology
Volume235
Issue number1
DOIs
StatePublished - Apr 22 1993

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Keywords

  • Clorgyline
  • Deprenyl
  • Fluoxetine
  • MDMA (3,4-methylenedioxymethamphetamine)
  • Nimodipine
  • Parachloroamphetamine
  • Reserpine

ASJC Scopus subject areas

  • Pharmacology

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