Agouti protein inhibits growth of B16 melanoma cells in vitro by acting through melanocortin receptors.
Agouti protein is known to antagonize cAMP formation, tyrosinase activation and melanogenesis in mouse B16-F1 melanoma cells induced by alpha-melanocyte-stimulating hormone (alpha-MSH). We now demonstrate that although agouti binds to the melanocortin receptor MC1-R with an almost identical affinity to that of alpha-MSH, it does not antagonize the inhibitory action of alpha-MSH on the growth of B16-F1 cells. Instead it has a similar antiproliferative action with a half-maximal effective concentration of 13 nM. In G4F cells lacking MC1-R, agouti is without effect. Agouti was also found to induce MC1-R down-regulation with identical kinetics and magnitude as alpha-MSH. Thus, the different effects of agouti on B16-F1 cells proceed via interaction with MC1-R but are not exclusively antagonistic.
Siegrist
W
W
Department of Research, University Hospital, Basel, Switzerland.
Willard
D H
DH
Wilkison
W O
WO
Eberle
A N
AN
D054366:Agouti Signaling Protein; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008543:Melanins / Q000096:biosynthesis; D008546:Melanoma, Experimental; D051379:Mice; D011506:Proteins / Q000494:pharmacology*; D018043:Receptors, Corticotropin / Q000187:drug effects / Q000502:physiology*; D044101:Receptors, Melanocortin; D014407:Tumor Cells, Cultured; D000521:alpha-MSH / Q000494:pharmacology
D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D011506:Proteins; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C515183:a protein, mouse; D000521:alpha-MSH