Document Detail


The role of the NOP receptor in regulating food intake, meal pattern, and the excitability of proopiomelanocortin neurons.
MedLine Citation:
PMID:  20510254     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We evaluated the role of the nociceptin/orphanin FQ (NOP) receptor in regulating food intake, meal pattern and the activity of hypothalamic arcuate (ARC) neurons. The microstructural analysis of food intake and meal pattern was performed under both food-deprived and ad libitum conditions. Whole-cell patch clamp recordings were obtained using the in vitro hypothalamic slice preparation and biocytin-filled electrodes. NOP receptor knockout mice exhibited significantly reduced body weight. Fasting-induced hyperphagia was diminished for the first 2h of a 6-h re-feeding period, and was associated with decreased meal duration and size, as well as a biphasic effect on meal frequency. The genotype effect observed under ad libitum conditions was comparatively unremarkable. Orphanin FQ/nociceptin (OFQ/N) was able to decrease evoked excitatory postsynaptic current amplitude, increase the S(2):S(1) ratio via the paired-pulse paradigm, and decrease miniature excitatory postsynaptic current frequency in ARC neurons from wild type animals but not NOP receptor knockouts. In addition OFQ/N activated a reversible outward current that was antagonized by the G-protein activated, inwardly-rectifying K(+) (GIRK) channel blocker tertiapin in wild type but not NOP knockout animals. Both the presynaptic and postsynaptic actions of OFQ/N were observed in ARC neurons subsequently determined to be immunopositive for characteristic phenotypic markers of anorexigenic proopiomelanocortin (POMC) neurons. Taken together, these results demonstrate the contribution of the NOP receptor in controlling food intake and meal pattern, as well as glutamate release and GIRK1 channel activity at POMC synapses.
Authors:
Borzoo Farhang; Lindsay Pietruszewski; Kabirullah Lutfy; Edward J Wagner
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-25
Journal Detail:
Title:  Neuropharmacology     Volume:  59     ISSN:  1873-7064     ISO Abbreviation:  Neuropharmacology     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-10-14     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  190-200     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Appetite Regulation / drug effects,  genetics*
Biophysics
Electric Stimulation / methods
Excitatory Postsynaptic Potentials / drug effects,  genetics*
Feeding Behavior / drug effects,  physiology*
G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism
Hypothalamus / cytology
Mice
Mice, Knockout
Neurons / drug effects,  physiology*
Opioid Peptides / pharmacology
Patch-Clamp Techniques / methods
Pro-Opiomelanocortin / metabolism*
Receptors, Opioid / deficiency,  metabolism*
Sodium Channel Blockers / pharmacology
Tetrodotoxin / pharmacology
Grant Support
ID/Acronym/Agency:
DA016882/DA/NIDA NIH HHS; HD058638/HD/NICHD NIH HHS; R01 HD058638/HD/NICHD NIH HHS; R01 HD058638-02/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/G Protein-Coupled Inwardly-Rectifying Potassium Channels; 0/Opioid Peptides; 0/Receptors, Opioid; 0/Sodium Channel Blockers; 0/nociceptin; 0/nociceptin receptor; 4368-28-9/Tetrodotoxin; 66796-54-1/Pro-Opiomelanocortin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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