3,4-methylenedioxymethamphetamine ('Ecstasy') promotes the translocation of protein kinase C (PKC): requirement of viable serotonin nerve terminals

H. Kenneth Kramer, Jose C P Poblete, Efrain C. Azmitia

Research output: Contribution to journalArticle

Abstract

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 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 × 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 to mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase activation may contribute to MDMA-induced serotonergic neurotoxicity.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBrain Research
Volume680
Issue number1-2
DOIs
StatePublished - May 22 1995

Fingerprint

N-Methyl-3,4-methylenedioxyamphetamine
Protein Kinase C
Serotonin
Membrane Proteins
p-Chloroamphetamine
Phorbol 12,13-Dibutyrate
Methamphetamine
Amphetamine
Cytosol
Phosphotransferases
Cell Membrane
Ligands
Injections
Therapeutics
Pharmaceutical Preparations

Keywords

  • Calcium
  • Degeneration
  • Release
  • Second messenger
  • Serotonin
  • Serotonin receptor

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

3,4-methylenedioxymethamphetamine ('Ecstasy') promotes the translocation of protein kinase C (PKC) : requirement of viable serotonin nerve terminals. / Kramer, H. Kenneth; Poblete, Jose C P; Azmitia, Efrain C.

In: Brain Research, Vol. 680, No. 1-2, 22.05.1995, p. 1-8.

Research output: Contribution to journalArticle

@article{407c6fd9c96e48e1903ec95ccb338b8b,
title = "3,4-methylenedioxymethamphetamine ('Ecstasy') promotes the translocation of protein kinase C (PKC): requirement of viable serotonin nerve terminals",
abstract = "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 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 × 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 to mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase activation may contribute to MDMA-induced serotonergic neurotoxicity.",
keywords = "Calcium, Degeneration, Release, Second messenger, Serotonin, Serotonin receptor",
author = "Kramer, {H. Kenneth} and Poblete, {Jose C P} and Azmitia, {Efrain C.}",
year = "1995",
month = "5",
day = "22",
doi = "10.1016/0006-8993(95)00199-Z",
language = "English (US)",
volume = "680",
pages = "1--8",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - 3,4-methylenedioxymethamphetamine ('Ecstasy') promotes the translocation of protein kinase C (PKC)

T2 - requirement of viable serotonin nerve terminals

AU - Kramer, H. Kenneth

AU - Poblete, Jose C P

AU - Azmitia, Efrain C.

PY - 1995/5/22

Y1 - 1995/5/22

N2 - 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 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 × 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 to mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase activation may contribute to MDMA-induced serotonergic neurotoxicity.

AB - 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 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 × 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 to mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase activation may contribute to MDMA-induced serotonergic neurotoxicity.

KW - Calcium

KW - Degeneration

KW - Release

KW - Second messenger

KW - Serotonin

KW - Serotonin receptor

UR - http://www.scopus.com/inward/record.url?scp=0029013304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029013304&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(95)00199-Z

DO - 10.1016/0006-8993(95)00199-Z

M3 - Article

C2 - 7663965

AN - SCOPUS:0029013304

VL - 680

SP - 1

EP - 8

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -