PMID- 21497613
OWN - NLM
STAT- MEDLINE
DCOM- 20120417
LR  - 20181201
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 61
IP  - 1-2
DP  - 2011 Jul-Aug
TI  - High concentrations of MDMA ('ecstasy') and its metabolite MDA inhibit calcium 
      influx and depolarization-evoked vesicular dopamine release in PC12 cells.
PG  - 202-8
LID - 10.1016/j.neuropharm.2011.03.028 [doi]
AB  - The popular synthetic drug of abuse 3,4-methylenedioxymethampetamine (MDMA) and 
      its metabolite 3,4-methylenedioxyamphetamine (MDA) act mainly on the serotonergic 
      system, though they also increase the amount of extracellular dopamine (DA) in 
      the brain, presumably via reversal of the membrane dopamine transporter (DAT). As 
      the involvement of exocytotic DA release is debated, we investigated if these 
      drugs alter the intracellular calcium concentration ([Ca(2+)](i)) and subsequent 
      DA exocytosis in single PC12 cells using respectively Fura-2 imaging and 
      amperometry. MDMA and MDA did not change basal [Ca(2+)](i) or exocytosis, but 
      inhibited depolarization-evoked increases in [Ca(2+)](i) and exocytosis following 
      15 min exposure to high concentrations of drugs (1 mM). Surprisingly, MDA was 
      more potent in inhibiting exocytosis than MDMA and already inhibited exocytosis 
      at concentrations that did not inhibit depolarization-evoked Ca(2+) influx 
      (10-100 muM). Without 15 min pre-exposure, both drugs failed to inhibit 
      depolarization-evoked Ca(2+) influx. These results indicate that at high 
      concentrations both MDMA and MDA inhibit exocytosis via indirect inhibition of 
      Ca(2+) influx, whereas at lower concentrations MDA may also reduce vesicle 
      cycling. Our data suggest that the DAT-independent increase in extracellular DA 
      in vivo is not due to direct stimulation of exocytosis, but rather to effects of 
      these drugs on other neurotransmitter systems that innervate the dopaminergic 
      system.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Hondebrink, Laura
AU  - Hondebrink L
AD  - Neurotoxicology Research Group, Institute for Risk Assessment Sciences (IRAS), 
      Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht, The Netherlands. 
      l.hondebrink@uu.nl
FAU - Meulenbelt, Jan
AU  - Meulenbelt J
FAU - Meijer, Marieke
AU  - Meijer M
FAU - van den Berg, Martin
AU  - van den Berg M
FAU - Westerink, Remco H S
AU  - Westerink RH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110407
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - SY7Q814VUP (Calcium)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*administration & dosage/metabolism
MH  - Animals
MH  - Calcium/*antagonists & inhibitors/*metabolism
MH  - Cell Survival/drug effects/physiology
MH  - Dopamine/*metabolism
MH  - Exocytosis/drug effects/physiology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage/metabolism
MH  - PC12 Cells
MH  - Rats
MH  - Synaptic Vesicles/drug effects/*metabolism
EDAT- 2011/04/19 06:00
MHDA- 2012/04/18 06:00
CRDT- 2011/04/19 06:00
PHST- 2010/10/22 00:00 [received]
PHST- 2011/01/28 00:00 [revised]
PHST- 2011/03/25 00:00 [accepted]
PHST- 2011/04/19 06:00 [entrez]
PHST- 2011/04/19 06:00 [pubmed]
PHST- 2012/04/18 06:00 [medline]
AID - S0028-3908(11)00145-6 [pii]
AID - 10.1016/j.neuropharm.2011.03.028 [doi]
PST - ppublish
SO  - Neuropharmacology. 2011 Jul-Aug;61(1-2):202-8. doi: 
      10.1016/j.neuropharm.2011.03.028. Epub 2011 Apr 7.