Document Detail

A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo.
MedLine Citation:
PMID:  9751529     Owner:  NLM     Status:  MEDLINE    
Agouti-related protein (Agrp) is present in rat and human hypothalamus and is structurally related to agouti protein. Overexpression of either of these proteins results in obesity. However the effect of exogenous Agrp and its in vivo interaction with alpha-melanocyte stimulating hormone (alphaMSH), the likely endogenous melanocortin 3 and 4 receptor (MC3-R and MC4-R) agonist, have not been demonstrated. We report that 1 nmol of Agrp(83-132), a C-terminal fragment of Agrp, when administered intracerebroventricularly (ICV) into rats, increased food intake over a 24-h period (23.0+/-1.4 g saline vs 32.9+/-2.3 g Agrp, p<0.05). The hyperphagia was similar to that seen when 1 nmol of the synthetic MC3-R and MC4-R antagonist SHU9119 was given i.c.v. (19.6+/-1.8 g saline vs 32.5+/-1.7 g SHU9119, p<0.001). Both Agrp(83-132) and SHU9119 blocked the reduction in 1-h food intake of i.c.v. alphaMSH at the beginning of the dark phase. This effect occurred independently of whether the antagonists were administered simultaneously, or nine hours prior, to the alphaMSH. We have also shown Agrp(83-132) is an antagonist at the MC3-R and MC4-R, with similar inhibition of cAMP activation to that previously reported for the full length peptide. In conclusion, Agrp(83-132) administered i.c.v. increases feeding with long lasting effects and is able to inhibit the action of alphaMSH. This interaction may be mediated by the MC3-R and/or MC4-R.
M Rossi; M S Kim; D G Morgan; C J Small; C M Edwards; D Sunter; S Abusnana; A P Goldstone; S H Russell; S A Stanley; D M Smith; K Yagaloff; M A Ghatei; S R Bloom
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Endocrinology     Volume:  139     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-10-08     Completed Date:  1998-10-08     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4428-31     Citation Subset:  AIM; IM    
Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
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MeSH Terms
Agouti Signaling Protein
Agouti-Related Protein
Dose-Response Relationship, Drug
Eating / drug effects*
Injections, Intraventricular
Intercellular Signaling Peptides and Proteins*
Peptide Fragments / pharmacology*
Proteins / pharmacology*
Rats, Wistar
Receptor, Melanocortin, Type 3
Receptors, Corticotropin / drug effects
alpha-MSH / antagonists & inhibitors*
Reg. No./Substance:
0/AGRP protein, human; 0/AGRP protein, rat; 0/ASIP protein, human; 0/Agouti Signaling Protein; 0/Agouti-Related Protein; 0/Asip protein, rat; 0/Intercellular Signaling Peptides and Proteins; 0/Peptide Fragments; 0/Proteins; 0/Receptor, Melanocortin, Type 3; 0/Receptors, Corticotropin; 581-05-5/alpha-MSH

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