Document Detail


Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246 attenuates the effect of endogenous and exogenous peptide YY(3-36) on food intake.
MedLine Citation:
PMID:  15862527     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The gastrointestinal-derived hormone peptide YY (PYY) is released from intestinal L-cells post-prandially in proportion to calorie intake, and modulates food intake. Peripheral administration of PYY((3-36)) reduces food intake and body weight in rodents and suppresses appetite and food intake in humans. PYY((3-36)) is hypothesised to inhibit food intake via activation of the auto-inhibitory pre-synaptic neuropeptide Y (NPY) Y2 receptor (Y2R) present on arcuate (ARC) NPY neurons. We aimed to investigate the feeding effect of PYY((3-36)) following blockade of ARC Y2R, using the specific receptor antagonist BIIE0246, in the rat. We found that pre-treatment with BIIE0246 (1 nmol) into the ARC attenuated the reduction in feeding observed following intraperitoneal injection of PYY((3-36)) (7.5 nmol/kg) (0-1 h food intake: BIIE0246/PYY((3-36)): 3.8 +/- 0.4 g; vs. Vehicle/PYY((3-36)): 2.7 +/- 0.2 g; P < 0.05). We found plasma PYY levels to be maximal at 120 min post-initiation of feeding. On investigation of the endogenous role of the Y2R, we found that ARC administration of BIIE0246 alone significantly increased feeding in satiated rats compared to vehicle-injected controls (0-1 h food intake: BIIE0246: 4.1 +/- 0.7 g; vs. vehicle: 1.7 +/- 0.7 g; P < 0.05), suggesting that Y2R antagonism disinhibits the NPY neuron thus stimulating feeding in otherwise satiated rats. These studies suggest that the Y2R plays an important role in post-prandial satiety and provide further insight into the mechanisms of action of PYY((3-36)).
Authors:
Caroline R Abbott; Caroline J Small; Adam R Kennedy; Nicola M Neary; Arshia Sajedi; Mohammad A Ghatei; Stephen R Bloom
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  1043     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-05-02     Completed Date:  2005-07-08     Revised Date:  2007-08-13    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  139-44     Citation Subset:  IM    
Affiliation:
Endocrine Unit, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 ONN, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Appetite / drug effects,  physiology
Arcuate Nucleus / cytology,  drug effects,  physiology
Arginine / analogs & derivatives*,  pharmacology*
Benzazepines / pharmacology*
Dose-Response Relationship, Drug
Drug Interactions
Eating / drug effects*,  physiology
Male
Neurons / drug effects,  physiology
Peptide YY / blood*,  pharmacology*
Rats
Rats, Wistar
Receptors, Neuropeptide Y / antagonists & inhibitors*
Satiation / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/BIIE 0246; 0/Benzazepines; 0/Receptors, Neuropeptide Y; 0/neuropeptide Y2 receptor; 106388-42-5/Peptide YY; 123583-37-9/peptide YY (3-36); 74-79-3/Arginine

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


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