| A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. | |
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MedLine Citation:
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PMID: 9751529 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Endocrinology Volume: 139 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 1998 Oct |
Date Detail:
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Created Date: 1998-10-08 Completed Date: 1998-10-08 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4428-31 Citation Subset: AIM; IM |
Affiliation:
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Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Agouti Signaling Protein Agouti-Related Protein Animals Dose-Response Relationship, Drug Eating / drug effects* Injections, Intraventricular Intercellular Signaling Peptides and Proteins* Male Peptide Fragments / pharmacology* Proteins / pharmacology* Rats Rats, Wistar Receptor, Melanocortin, Type 3 Receptors, Corticotropin / drug effects alpha-MSH / antagonists & inhibitors* |
| Chemical | |
Reg. No./Substance:
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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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