Agouti-related protein (AGRP) is a naturally occurring antagonist of the brain melanocortin receptors (MC3R and MC4R) and is physiologically implicated as participating in feeding behavior and energy homeostasis. The human AGRP decapeptide Yc[CRFFNAFC]Y has been previously reported as binding to the human MC3 and MC4 receptors and antagonizing the MC4 receptor. We have synthesized this decapeptide and pharmacologically characterized it at the murine melanocortin receptors and found it to possess MC4R antagonist activity (pA2 = 6.8) and, unexpectedly, MC1R agonist activity (EC50 = 2.89 μM). This study characterizes the first AGRP-based peptide agonist at the melanocortin receptors. Copyright (C) 2000 Elsevier Science Inc.
Bibliographical noteFunding Information:
This work has been funded by the Howard Hughes Medical Institute Research Resources Program, University of Florida. C.H.-L. is a recipient of a Burroughs Wellcome fund Career Award in the Biomedical Sciences.
- Agouti-related protein
- α-Melanocyte stimulating hormone