title: ART (protein product of agouti-related transcript) as an antagonist of MC-3 and MC-4 receptors.
abstract: 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.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065, USA. tung_fong@merck.com
authors.forename: T M
authors.initials: TM
authors.lastname: Fong
authors.forename: C
authors.initials: C
authors.lastname: Mao
authors.forename: T
authors.initials: T
authors.lastname: MacNeil
authors.forename: R
authors.initials: R
authors.lastname: Kalyani
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Weinberg
authors.forename: M R
authors.initials: MR
authors.lastname: Tota
authors.forename: L H
authors.initials: LH
authors.lastname: Van der Ploeg
mesh_terms: D054369:Agouti-Related Protein; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology*; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors*; D044101:Receptors, Melanocortin; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D014162:Transfection; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D018000:Receptors, Peptide; D011994:Recombinant Proteins; C086971:melanocortin 5 receptor; D000521:alpha-MSH; D000242:Cyclic AMP