Document Detail


Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.
MedLine Citation:
PMID:  9854049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The new neuropeptide Y (NPY) Y5 receptor antagonist CGP 71683A displayed high affinity for the cloned rat NPY Y5 subtype, but > 1, 000-fold lower affinity for the cloned rat NPY Y1, Y2, and Y4 subtypes. In LMTK cells transfected with the human NPY Y5 receptor, CGP 71683A was without intrinsic activity and antagonized NPY-induced Ca2+ transients. CGP 71683A was given intraperitoneally (dose range 1-100 mg/kg) to a series of animal models of high hypothalamic NPY levels. In lean satiated rats CGP 71683A significantly antagonized the increase in food intake induced by intracerebroventricular injection of NPY. In 24-h fasted and streptozotocin diabetic rats CGP 71683A dose-dependently inhibited food intake. During the dark phase, CGP 71683A dose-dependently inhibited food intake in free-feeding lean rats without affecting the normal pattern of food intake or inducing taste aversion. In free-feeding lean rats, intraperitoneal administration of CGP 71683A for 28 d inhibited food intake dose-dependently with a maximum reduction observed on days 3 and 4. Despite the return of food intake to control levels, body weight and the peripheral fat mass remained significantly reduced. The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite.
Authors:
L Criscione; P Rigollier; C Batzl-Hartmann; H Rüeger; A Stricker-Krongrad; P Wyss; L Brunner; S Whitebread; Y Yamaguchi; C Gerald; R O Heurich; M W Walker; M Chiesi; W Schilling; K G Hofbauer; N Levens
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  102     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-02-01     Completed Date:  1999-02-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2136-45     Citation Subset:  AIM; IM    
Affiliation:
Metabolic and Cardiovascular Diseases Research, Novartis Pharma AG, CH-4002 Basel, Switzerland. Leoluca.criscione@pharma,novartis.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Appetite Regulation / physiology*
Binding, Competitive
Blood Glucose / metabolism
Body Composition / drug effects
Body Weight / drug effects
Calcium / metabolism
Cell Line
Conditioning (Psychology) / drug effects
Diabetes Mellitus, Experimental / physiopathology
Drinking / drug effects
Eating / drug effects
Humans
Hypothalamus / metabolism,  physiology
Insulin / blood,  pharmacology
Male
Mice
Naphthalenes / pharmacology*
Neuropeptide Y / metabolism*
Pyrimidines / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Neuropeptide Y / metabolism,  physiology*
Triglycerides / blood
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/CGP 71683 A; 0/Naphthalenes; 0/Neuropeptide Y; 0/Pyrimidines; 0/Receptors, Neuropeptide Y; 0/Triglycerides; 0/neuropeptide Y5 receptor; 11061-68-0/Insulin; 7440-70-2/Calcium
Comments/Corrections

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


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