Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain.

D. Bagnol, Xinyun Lu, C. B. Kaelin, H. E. Day, M. Ollmann, I. Gantz, H. Akil, G. S. Barsh, S. J. Watson

Research output: Contribution to journalArticle

267 Scopus citations

Abstract

Agouti-related protein (AGRP) is a recently discovered orexigenic neuropeptide that inhibits the binding and action of alpha-melanocyte-stimulating hormone derived from proopiomelanocortin (POMC) at the melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) and has been proposed to function primarily as an endogenous melanocortin antagonist. To better understand the interplay between the AGRP and melanocortin signaling systems, we compared their nerve fiber distributions with each other by immunohistochemistry and their perikarya distribution with MC3R and MC4R by double in situ hybridization. Although deriving from distinct cell groups, AGRP and melanocortin terminals project to identical brain areas. Both AGRP and melanocortin neurons selectively express the MC3R, which provides a neuroanatomical basis for a dual-input circuit with biological amplification and feedback inhibition. These studies highlight a broader complexity in POMC-mediated behavior in the brain.

Original languageEnglish (US)
Pages (from-to)RC26
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume19
Issue number18
DOIs
StatePublished - Sep 15 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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