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• W1479662652 endingPage "129" @default.
• W1479662652 startingPage "117" @default.
• W1479662652 abstract "This report further characterizes the intermediate metabolic effects of the psychotropic amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”), on the activity of second messenger-dependent kinases. Previous work has demonstrated that two injections of MDMA (20 mg/kg) elicits a prolonged translocation of the calcium and phospholipid-dependent enzyme, protein kinase C (PKC) in rats. However, because MDMA has actions at the 5-HT transporter and 5-HT2A/2C receptors, our experiments were directed at uncovering which of these many sites may be involved in this second messenger-dependent response. A single injection of MDMA produced a time- and dose-dependent increase in the density of cortical and hippocampal PKC (as measured by 3H-phorbol 12,13-dibutyrate (PDBu)) binding sites. MDMA-mediated PKC translocation was long-lasting and remained above control (saline-treated rats) for up to 24 h after injection. This effect was mimicked by another substituted amphetamine, p-chloroamphetamine (pCA), but with a temporal-response curve that was to the left of MDMA’s. However, pure uptake inhibitors like fluoxetine, cocaine, and the selective 5-HT2A/2C agonist, DOB, were unable to produce a long-lasting translocation of PKC binding sites in rat cortex. Fluoxetine, a selective serotonin uptake inhibitor (SSRI) and ketanserin, a 5-HT2A antagonist, attenuated PKC translocation by MDMA with differing efficacies; however, both compounds completely prevented the loss of 5-HT uptake sties after multiple doses of MDMA. These results suggest that MDMA increases PKC translocation by two interrelated mechanisms that involve 5-HT2A/2C receptors and the 5-HT transporter. This pathway appears to include: (1) the drug binding to the 5-HT transporter, (2) the release of cytosolic 5-HT stores into the extracellular space, and (3) the activation of post-synaptic 5-HT2A/2C receptors linked to G-protein-mediated phospholipid hydrolysis." @default.
• W1479662652 created "2016-06-24" @default.
• W1479662652 creator A5013965489 @default.
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• W1479662652 date "1997-09-01" @default.
• W1479662652 modified "2023-10-16" @default.
• W1479662652 title "Activation of Protein Kinase C (PKC) by 3,4-Methylenedioxymethamphetamine (MDMA) Occurs Through the Stimulation of Serotonin Receptors and Transporter" @default.
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• W1479662652 doi "https://doi.org/10.1016/s0893-133x(97)00026-2" @default.
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• W1479662652 hasPublicationYear "1997" @default.
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