PMID- 21502286
OWN - NLM
STAT- MEDLINE
DCOM- 20120413
LR  - 20231213
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 589
IP  - Pt 13
DP  - 2011 Jul 1
TI  - Nociceptin/orphanin FQ suppresses the excitability of neurons in the ventromedial 
      nucleus of the hypothalamus.
PG  - 3103-14
LID - 10.1113/jphysiol.2011.208819 [doi]
AB  - Nociceptin or orphanin FQ (N/OFQ) stimulates food intake when injected into the 
      ventromedial nucleus of the hypothalamus (VMN). The VMN negatively regulates 
      energy balance in part by tonically activating proopiomelanocortin arcuate 
      neurons, thereby suppressing food intake. However, it is not clear how orexigenic 
      neurotransmission within the VMN can stimulate food intake. We tested the 
      hypothesis that the orexigenic action of N/OFQ results from its inhibition of 
      anorexigenic VMN neurons. We studied the effects of N/OFQ on the electrical 
      properties of anorexigenic VMN neurons in acute brain slices. Ionic mechanisms 
      underlying the actions of N/OFQ were studied using whole cell patch-clamp 
      recordings from VMN neurons expressing the anorexigenic leptin receptor (LepRb). 
      Bath application of N/OFQ to LepRb-expressing VMN neurons elicited a robust, 
      reversible membrane hyperpolarization that suppressed neuronal excitability by 
      raising the action potential firing threshold and cell rheobase. N/OFQ activated 
      a postsynaptic, G-protein coupled, inwardly rectifying potassium (GIRK) current 
      that was sensitive to G-protein inactivation, blocked by the GIRK blocker 
      SCH23390, and occluded by the GABAB agonist and potent GIRK activator, baclofen. 
      Application of the selective N/OFQ receptor antagonist SB-612111 blocked the 
      inhibitory effects of N/OFQ. We concluded that N/OFQ directly inhibited VMN 
      neurons by activating a GIRK. These results implicate the site-specific 
      contributions of orexigenic neuropeptides at VMN neurons to suppress anorexigenic 
      output. This study thus advances our understanding regarding the contributions of 
      the VMN to hypothalamic regulation of energy balance.
FAU - Chee, Melissa J
AU  - Chee MJ
AD  - Centre for Neuroscience, University of Alberta, Edmonton, Alberta T6G 2H7, 
      Canada.
FAU - Price, Christopher J
AU  - Price CJ
FAU - Statnick, Michael A
AU  - Statnick MA
FAU - Colmers, William F
AU  - Colmers WF
LA  - eng
GR  - MT10520/Canadian Institutes of Health Research/Canada
GR  - OTG 88592/Canadian Institutes of Health Research/Canada
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110418
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Cycloheptanes)
RN  - 0 (Opioid Peptides)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, Leptin)
RN  - 0 
      (cis-1-methyl-7-((4-(2,6-dichlorophenyl)piperidin-1-yl)methyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol)
RN  - 0 (leptin receptor, mouse)
SB  - IM
MH  - Action Potentials/drug effects/*physiology
MH  - Animals
MH  - Cycloheptanes/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neurons/drug effects/*physiology
MH  - Opioid Peptides/antagonists & inhibitors/*physiology
MH  - Piperidines/pharmacology
MH  - Receptors, Leptin/biosynthesis
MH  - Ventromedial Hypothalamic Nucleus/drug effects/*physiology
MH  - Nociceptin
PMC - PMC3145927
EDAT- 2011/04/20 06:00
MHDA- 2012/04/14 06:00
PMCR- 2012/07/01
CRDT- 2011/04/20 06:00
PHST- 2011/04/20 06:00 [entrez]
PHST- 2011/04/20 06:00 [pubmed]
PHST- 2012/04/14 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - jphysiol.2011.208819 [pii]
AID - 10.1113/jphysiol.2011.208819 [doi]
PST - ppublish
SO  - J Physiol. 2011 Jul 1;589(Pt 13):3103-14. doi: 10.1113/jphysiol.2011.208819. Epub 
      2011 Apr 18.