Document Detail

Nociceptin induces hypophagia in the perifornical and lateral hypothalamic area.
MedLine Citation:
PMID:  23028954     Owner:  NLM     Status:  MEDLINE    
Nociceptin/orphanin FQ (N/OFQ) is known to induce food intake when administered into the lateral ventricle or certain brain areas. This is somewhat contradictory to its reward-suppressing role, as food is a strong rewarding stimulus. This discrepancy may be due to the functional diversity of N/OFQ's target brain areas. N/OFQ has been shown to inhibit orexin and melanin-concentrating hormone (MCH) neurons, both of which are appetite-inducing cells. As the expression of these neurons is largely confined to the lateral hypothalamus/perifornical area (LH/PFA), we hypothesized that N/OFQ inhibits food intake by acting in this area. To test this hypothesis, we examined the effect of local N/OFQ infusion within the LH/PFA on food intake in the rat and found that N/OFQ decreased sugar pellet as well as chow intake. This effect was not seen when the injection site was outside of the LH/PFA, suggesting a site-specific effect. Next, to determine a possible cellular mechanism of N/OFQ action on food intake, whole cell patch clamp recordings were performed on rat orexin neurons. As previously reported in mice, N/OFQ induced a strong and long lasting hyperpolarization. Pharmacological study indicated that N/OFQ directly inhibited orexin neurons by activating ATP-sensitive potassium (KATP) channels. This effect was partially but significantly attenuated by the inhibitors of PI3K, PKC and PKA, suggesting that the N/OFQ signaling is mediated by these protein kinases. In summary, our results demonstrate a KATP channel-dependent N/OFQ signaling and that N/OFQ is a site-specific anorexic peptide.
Matthew P Parsons; Julia Burt; Amanda Cranford; Christian Alberto; Katrin Zipperlen; Michiru Hirasawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-17
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-25     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e45350     Citation Subset:  IM    
Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada.
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MeSH Terms
Eating / drug effects*
Hypothalamic Area, Lateral / drug effects*,  metabolism
KATP Channels / metabolism
Neurons / drug effects,  metabolism
Opioid Peptides / pharmacology*
Rats, Sprague-Dawley
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/KATP Channels; 0/Opioid Peptides; 0/nociceptin

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