Document Detail

Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin.
MedLine Citation:
PMID:  23348063     Owner:  NLM     Status:  MEDLINE    
The opioid system is well recognized as an important regulator of appetite and energy balance. We now hypothesized that the hypothalamic opioid system might modulate the orexigenic effect of ghrelin. Using pharmacological and gene silencing approaches, we demonstrate that ghrelin utilizes a hypothalamic κ-opioid receptor (KOR) pathway to increase food intake in rats. Pharmacological blockade of KOR decreases the acute orexigenic effect of ghrelin. Inhibition of KOR expression in the hypothalamic arcuate nucleus is sufficient to blunt ghrelin-induced food intake. By contrast, the specific inhibition of KOR expression in the ventral tegmental area does not affect central ghrelin-induced feeding. This new pathway is independent of ghrelin-induced AMP-activated protein kinase activation, but modulates the levels of the transcription factors and orexigenic neuropeptides triggered by ghrelin to finally stimulate feeding. Our novel data implicate hypothalamic KOR signaling in the orexigenic action of ghrelin.
Amparo Romero-Picó; Maria J Vázquez; David González-Touceda; Cintia Folgueira; Karolina P Skibicka; Mayte Alvarez-Crespo; Margriet A Van Gestel; Douglas A Velásquez; Christoph Schwarzer; Herbert Herzog; Miguel López; Roger A Adan; Suzanne L Dickson; Carlos Diéguez; Rubén Nogueiras
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  38     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-15     Completed Date:  2014-01-24     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1296-307     Citation Subset:  IM    
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MeSH Terms
Agouti-Related Protein / metabolism
Arcuate Nucleus / drug effects,  metabolism,  physiology*
Conditioning, Operant / drug effects,  physiology*
Drug Interactions
Eating / drug effects,  physiology*
Enkephalins / metabolism
Gene Silencing
Ghrelin / antagonists & inhibitors,  physiology*
Infusions, Intraventricular
Intracellular Signaling Peptides and Proteins / metabolism
Narcotic Antagonists / administration & dosage,  pharmacology
Neuropeptide Y / metabolism
Neuropeptides / metabolism
Protein Precursors / metabolism
Receptors, Ghrelin / metabolism,  physiology
Receptors, Opioid, kappa / antagonists & inhibitors,  genetics,  metabolism,  physiology*
Reinforcement Schedule
Signal Transduction / drug effects,  physiology
Ventral Tegmental Area / drug effects,  metabolism,  physiology
Reg. No./Substance:
0/Agouti-Related Protein; 0/Enkephalins; 0/Ghrelin; 0/Intracellular Signaling Peptides and Proteins; 0/Narcotic Antagonists; 0/Neuropeptide Y; 0/Neuropeptides; 0/Protein Precursors; 0/Receptors, Ghrelin; 0/Receptors, Opioid, kappa; 0/orexins; 93443-35-7/preproenkephalin

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

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