ART (protein product of agouti-related transcript) as an antagonist of MC-3 and MC-4 receptors

Biochem Biophys Res Commun. 1997 Aug 28;237(3):629-31. doi: 10.1006/bbrc.1997.7200.


The mRNA encoding an agouti related protein (ART) of unknown biochemical function was previously reported to be up-regulated in the hypothalamus of two genetically obese mouse strains. We have expressed human ART as a secreted protein in COS-7 cells, and show that recombinant ART is functionally active in inhibiting the binding of a radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analog to the human melanocortin-3 (MC-3) and melanocortin-4 (MC-4) receptors, while it is not a potent inhibitor of the human melanocortin-5 (MC-5) receptor. ART is an antagonist of the human MC-3 and MC-4 receptors as determined in functional assay. ART appears to be approximately 100-fold more potent than agouti with reference to the MC-3R and MC-4R binding affinity. These data suggest that ART may be a physiological regulator of feeding behavior.

MeSH terms

  • Agouti-Related Protein
  • Animals
  • Base Sequence
  • COS Cells
  • Cyclic AMP / metabolism
  • DNA Primers
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Proteins / pharmacology*
  • Receptor, Melanocortin, Type 3
  • Receptor, Melanocortin, Type 4
  • Receptors, Corticotropin / antagonists & inhibitors*
  • Receptors, Melanocortin
  • Receptors, Peptide / antagonists & inhibitors*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology
  • Transfection
  • alpha-MSH / metabolism*


  • AGRP protein, human
  • Agouti-Related Protein
  • Agrp protein, mouse
  • DNA Primers
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • Receptor, Melanocortin, Type 3
  • Receptor, Melanocortin, Type 4
  • Receptors, Corticotropin
  • Receptors, Melanocortin
  • Receptors, Peptide
  • Recombinant Proteins
  • melanocortin 5 receptor
  • alpha-MSH
  • Cyclic AMP