PMID- 17995929
OWN - NLM
STAT- MEDLINE
DCOM- 20080214
LR  - 20131121
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 104
IP  - 4
DP  - 2008 Feb
TI  - Minoxidil prevents 3,4-methylenedioxymethamphetamine-induced serotonin 
      depletions: role of mitochondrial ATP-sensitive potassium channels, Akt and ERK.
PG  - 914-25
AB  - Preconditioning has emerged as a valid strategy against different neurotoxic 
      insults. Although the mechanisms underlying preconditioning are not fully 
      understood, the activation of ATP-sensitive potassium (KATP) channels has been 
      proposed to play a pivotal role in neuronal preconditioning. In the present work 
      we examine whether minoxidil a KATP channel activator protects against the 
      long-term toxicity caused by the amphetamine derivative 
      3,4-methylenedioxymethamphetamine (MDMA) in rats. Our data show that 
      intrastriatal administration of minoxidil prevents MDMA-induced long-term indole 
      depletions in the rat striatum. This effect was not related to an effect on core 
      temperature, as pre-treatment with minoxidil did not significantly alter 
      MDMA-induced hyperthermia. Taking into account that minoxidil opens both 
      sarcolemmal and mitochondrial KATP channels, we examined the role of each type of 
      channels in the protective effects of minoxidil using specific inhibitors. The 
      administration of HMR-1098, a blocker of the sarcolemmal KATP channels, along 
      with minoxidil did not affect the protection afforded by the latter. On the 
      contrary the selective mitochondrial KATP channel blocker 5-hydroxydecanoic acid 
      completely reversed the protection afforded by minoxidil, thereby implicating the 
      involvement of mitochondrial (but not sarcolemmal) KATP channels. Furthermore our 
      data show the participation of Akt and extracellular signal-regulated kinases in 
      minoxidil-afforded protection. Intrastriatal administration of wortmannin or 
      PD98059 (inhibitors of phosphatidylinositol-3-kinase and mitogen-activated 
      protein kinase/extracellular regulated protein kinase, respectively), along with 
      minoxidil abolished the protective effect of minoxidil against the serotonergic 
      toxicity caused by MDMA. These results demonstrate that minoxidil by opening 
      mitochondrial KATP channels completely prevents MDMA toxicity and that Akt and 
      MAP kinases are involved in minoxidil-afforded neuroprotection.
FAU - Goni-Allo, Beatriz
AU  - Goni-Allo B
AD  - Department of Pharmacology, School of Medicine, University of Navarra, Spain.
FAU - Puerta, Elena
AU  - Puerta E
FAU - Ramos, Maria
AU  - Ramos M
FAU - Lasheras, Berta
AU  - Lasheras B
FAU - Jordan, Joaquin
AU  - Jordan J
FAU - Aguirre, Norberto
AU  - Aguirre N
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071106
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (KATP Channels)
RN  - 0 (Potassium Channels)
RN  - 0 (mitochondrial K(ATP) channel)
RN  - 333DO1RDJY (Serotonin)
RN  - 5965120SH1 (Minoxidil)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Extracellular Signal-Regulated MAP Kinases/*physiology
MH  - KATP Channels/*physiology
MH  - Male
MH  - Minoxidil/*pharmacology
MH  - Mitochondria/drug effects/physiology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/antagonists & inhibitors/*pharmacology
MH  - Potassium Channels/physiology
MH  - Proto-Oncogene Proteins c-akt/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/*deficiency/metabolism
EDAT- 2007/11/13 09:00
MHDA- 2008/02/15 09:00
CRDT- 2007/11/13 09:00
PHST- 2007/11/13 09:00 [pubmed]
PHST- 2008/02/15 09:00 [medline]
PHST- 2007/11/13 09:00 [entrez]
AID - JNC5042 [pii]
AID - 10.1111/j.1471-4159.2007.05042.x [doi]
PST - ppublish
SO  - J Neurochem. 2008 Feb;104(4):914-25. doi: 10.1111/j.1471-4159.2007.05042.x. Epub 
      2007 Nov 6.