PMID- 9272479
OWN - NLM
STAT- MEDLINE
DCOM- 19980108
LR  - 20221207
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 17
IP  - 3
DP  - 1997 Sep
TI  - Activation of protein kinase C (PKC) by 3,4-methylenedioxymethamphetamine (MDMA) 
      occurs through the stimulation of serotonin receptors and transporter.
PG  - 117-29
AB  - 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.
FAU - Kramer, H K
AU  - Kramer HK
AD  - Department of Psychiatry, New York University Medical Center, NY 10016, USA.
FAU - Poblete, J C
AU  - Poblete JC
FAU - Azmitia, E C
AU  - Azmitia EC
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0 (Slc6a4 protein, rat)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 37558-16-0 (Phorbol 12,13-Dibutyrate)
RN  - 97F9DE4CT4 (Ketanserin)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Brain/*drug effects/metabolism
MH  - Brain Stem/drug effects/metabolism
MH  - Carrier Proteins/*metabolism
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Enzyme Activation
MH  - Female
MH  - Fluoxetine/pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Ketanserin/pharmacology
MH  - Membrane Glycoproteins/*metabolism
MH  - *Membrane Transport Proteins
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - *Nerve Tissue Proteins
MH  - Phorbol 12,13-Dibutyrate/metabolism
MH  - Protein Kinase C/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/drug effects/*metabolism
MH  - Serotonin Agents/*pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
EDAT- 1997/09/01 00:00
MHDA- 1997/09/01 00:01
CRDT- 1997/09/01 00:00
PHST- 1997/09/01 00:00 [pubmed]
PHST- 1997/09/01 00:01 [medline]
PHST- 1997/09/01 00:00 [entrez]
AID - S0893133X97000262 [pii]
AID - 10.1016/S0893-133X(97)00026-2 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 1997 Sep;17(3):117-29. doi: 
      10.1016/S0893-133X(97)00026-2.