Cited by 580Regulation of Appetite and ObesityNeuropeptides and Animal PhysiologyHypothalamic control of reproductive hormones

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A C-Terminal Fragment of Agouti-Related Protein Increases Feeding and Antagonizes the Effect of Alpha-Melanocyte Stimulating Hormone in Vivo

Rossi, M., Kim, M. S., Morgan, D. G. A., Small, C. J., Edwards, C. M. B., Sunter, D., Abusnana, S., Goldstone, A. P., Russell, S. H., Stanley, S. A., Smith, D. M., Yagaloff, K., Ghatei, M. A., Bloom, S. R.·1998·Endocrinology

DOI 10.1210/endo.139.10.6332

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Abstract

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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“AGRP is co-localised with NPY in the arcuate nucleus, and stimulates food intake by antagonistic action at melanocortin MC4 receptors in the hypothalamus ( Rossi et al. 1998 ).”
Background
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Assessing Interactions Between Ghsr and Mc3r Reveals a Role for AgRP in the Expression of Food Anticipatory Activity in Male Mice
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Background
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Authors: Rossi, M., Kim, M. S., Morgan, D. G. A., Small, C. J., Edwards, C. M. B., Sunter, D., Abusnana, S., Goldstone, A. P., Russell, S. H., Stanley, S. A., Smith, D. M., Yagaloff, K., Ghatei, M. A., & Bloom, S. R.
Affiliations: Hammersmith Hospital (GB)
ORCID: Abusnana, S.
Goldstone, A. P.
Stanley, S. A.
Smith, D. M.
Bloom, S. R.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1998-10
Volume: 139
Issue: 10
Pages: 4428-4431
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.139.10.6332
OpenAlex: W2171010063
Cited by: 576
References: 0
Citations by year: 2026: 2 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 11 · 2020: 7 · 2019: 16 · 2018: 8 · 2017: 13 · 2016: 16 · 2015: 15 · 2014: 16 · 2013: 22 · 2012: 29
FWCI: 11.74
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: agouti-related protein, C-terminal fragment, alpha-melanocyte-stimulating hormone, melanocortin 3 receptor, melanocortin-4 receptor, dietary intake, hyperphagia, SHU9119, obesity, hypothalamus, cAMP signaling, intracerebroventricular administration
MeSH terms: alpha-MSH, Animals, Dose-Response Relationship, Drug, Eating, Injections, Intraventricular, Male, Peptide Fragments, Proteins, Rats, Wistar, Receptors, Corticotropin, Intercellular Signaling Peptides and Proteins, Receptor, Melanocortin, Type 3, Rats, Agouti Signaling Protein, Agouti-Related Protein

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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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