3,4-Methylenedioxymethamphetamine ('Ecstasy') promotes the translocation of protein kinase C (PKC): requirement of viable serotonin nerve terminals.
The metabolic effects of the neurotoxic, ring-substituted amphetamine 3,4-methylenedioxy-methamphetamine (MDMA or 'Ecstasy') were examined in vivo. In this study, we focused on the ability of MDMA to induce a translocation of the calcium and phospholipid-dependent protein kinase C (PKC) from the cytosol to the cortical plasma membrane. Two injections of MDMA (20 mg/kg; 10 h apart; s.c.) increased the density of membrane bound PKC sites by 48.0% over saline treated animals without mediating a significant change in ligand ([3H]phorbol 12,13 dibutyrate; [3H]PDBu) affinity. Longer drug treatments (8 x 20 mg/kg) induced a lasting (up to 5 days post-treatment) increase in the density of membrane-bound PKC. Prior destruction of cortical 5-HT nerve terminals with p-chloroamphetamine (PCA) prevents this effect and suggests that viable 5-HT uptake sites are essential for MDMA-induced PKC translocation. These results demonstrate that MDMA-induced PKC translocation is mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase activation may contribute to MDMA-induced serotonergic neurotoxicity.
Kramer
H K
HK
Department of Biology, New York University, NY 10003, USA.
Poblete
J C
JC
Azmitia
E C
EC
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009410:Nerve Degeneration; D009411:Nerve Endings / Q000473:pathology / Q000502:physiology*; D017374:Paroxetine / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*
D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D017374:Paroxetine; D011493:Protein Kinase C; D018817:N-Methyl-3,4-methylenedioxyamphetamine