PMID- 21886598
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20111110
LR  - 20211020
IS  - 1875-6190 (Electronic)
IS  - 1570-159X (Print)
IS  - 1570-159X (Linking)
VI  - 9
IP  - 1
DP  - 2011 Mar
TI  - Inhibition of g protein-activated inwardly rectifying k channels by 
      phencyclidine.
PG  - 244-6
LID - 10.2174/157015911795017407 [doi]
AB  - Addictive drugs, such as opioids, ethanol, cocaine, amphetamine, and 
      phencyclidine (PCP), affect many functions of the nervous system and peripheral 
      organs, resulting in severe health problems. G protein-activated inwardly 
      rectifying K(+) (GIRK, Kir3) channels play an important role in regulating 
      neuronal excitability through activation of various Gi/o protein-coupled 
      receptors including opioid and CB(1) cannabinoid receptors. Furthermore, the 
      channels are directly activated by ethanol and inhibited by cocaine at toxic 
      levels, but not affected by methylphenidate, methamphetamine, and 
      3,4-methylenedioxymethamphetamine (MDMA) at toxic levels. The primary 
      pharmacological action of PCP is blockade of N-methyl-D-aspartate (NMDA) receptor 
      channels that are associated with its psychotomimetic effects. PCP also interacts 
      with several receptors and channels at relatively high concentrations. However, 
      the molecular mechanisms underlying the various effects of PCP remain to be 
      clarified. Here, we investigated the effects of PCP on GIRK channels using the 
      Xenopus oocyte expression system. PCP weakly but significantly inhibited GIRK 
      channels at micromolar concentrations, but not Kir1.1 and Kir2.1 channels. The 
      PCP concentrations effective in inhibiting GIRK channels overlap clinically 
      relevant brain concentrations in severe intoxication. The results suggest that 
      partial inhibition of GIRK channels by PCP may contribute to some of the toxic 
      effects after overdose.
FAU - Kobayashi, Toru
AU  - Kobayashi T
AD  - Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, 
      Setagaya-ku, Tokyo 156-8585, Japan.
FAU - Nishizawa, Daisuke
AU  - Nishizawa D
FAU - Ikeda, Kazutaka
AU  - Ikeda K
LA  - eng
PT  - Journal Article
PL  - United Arab Emirates
TA  - Curr Neuropharmacol
JT  - Current neuropharmacology
JID - 101157239
PMC - PMC3137191
OTO - NOTNLM
OT  - GIRK channel
OT  - Kir channel
OT  - Phencyclidine
OT  - Xenopus oocyte.
OT  - intoxication
EDAT- 2011/09/03 06:00
MHDA- 2011/09/03 06:01
PMCR- 2011/09/01
CRDT- 2011/09/03 06:00
PHST- 2009/10/01 00:00 [received]
PHST- 2010/04/17 00:00 [revised]
PHST- 2010/05/26 00:00 [accepted]
PHST- 2011/09/03 06:00 [entrez]
PHST- 2011/09/03 06:00 [pubmed]
PHST- 2011/09/03 06:01 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - CN-9-244 [pii]
AID - 10.2174/157015911795017407 [doi]
PST - ppublish
SO  - Curr Neuropharmacol. 2011 Mar;9(1):244-6. doi: 10.2174/157015911795017407.