Integrative transporter-mediated release from cytoplasmic and vesicular 5-hydroxytryptamine stores in cultured neurons.
X F Gu, E C Azmitia
European Journal of Pharmacology April 22, 1993 DOI: 10.1016/0014-2999(93)90819-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro microculture study Peer reviewed |
|---|---|
| Population | Fetal serotonin (5-HT) neurons in microculture |
| Interventions | MDMA p-chloroamphetamine (PCA) fluoxetine deprenyl reserpine nimodipine |
| Dose | Deprenyl 10(-7) M; reserpine 10(-9) M; nimodipine 10(-8) M |
| Key points | MDMA and PCA release serotonin from cultured fetal serotonin neurons via the serotonin transporter, a process blocked by fluoxetine and attenuated by reserpine and nimodipine. Both compounds also inhibit MAO-A, and deprenyl potentiates their release. The authors conclude the release draws serotonin from the cytoplasm and may incorporate vesicular stores. |
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, 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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- The mechanisms involved in the long‐lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy’)‐induced degeneration of 5‐HT nerve endings in rat brain British Journal of Pharmacology September 1, 2001
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- Release of serotonin induced by 3,4-methylenedioxymethamphetamine (MDMA) and other substituted amphetamines in cultured fetal raphe neurons: further evidence for calcium-independent mechanisms of release Brain Research October 1, 1995
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- The substituted amphetamines 3,4-methylenedioxymethamphetamine, methamphetamine, p-chloroamphetamine and fenfluramine induce 5-hydroxytryptamine release via a common mechanism blocked by fluoxetine and cocaine European Journal of Pharmacology May 1, 1992
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