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The Journal of Neuroscience, 1999, 19:RC26:1-7
RAPID COMMUNICATION
Anatomy of an Endogenous Antagonist: Relationship between Agouti-Related Protein and Proopiomelanocortin in BrainDidier Bagnol1, 4, Xin-Yun Lu1, Christopher B. Kaelin3, Heidi E. W. Day1, Michael Ollmann3, Ira Gantz2, Huda Akil1, Gregory S. Barsh3, and Stanley J. Watson1 1 Mental Health Research Institute and 2 Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109-0720, 3 Departments of Pediatrics and Genetics, Howard Hughes Medical Institute, Stanford, California 94305, and 4 Centre National de la Recherche Scientifique, Neurobiologie des Fonctions Végétatives, Université d'Aix-Marseille, Marseille 3, Cedex 20, France
Agouti-related protein (AGRP) is a recently discovered orexigenic neuropeptide that inhibits the binding and action of
-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.
Key words: Agouti-related protein; proopiomelanocortin; ingestive behavior; MC3R; MC4R; arcuate nucleus
Copyright © 0000 Society for Neuroscience 0270-6474/0/$05.00/0
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