AGOUTI PROTEIN INHIBITS GROWTH OF B16 MELANOMA-CELLS IN-VITRO BY ACTING THROUGH MELANOCORTIN RECEPTORS

Agouti protein is known to antagonize cAMP formation, tyrosinase activ ation and melanogenesis in mouse B16-F1 melanoma cells induced by alph a-melanocyte-stimulating hormone (alpha-MSH). We now demonstrate that although agouti binds to the melanocortin receptor MC1-R with an almos t 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 effectiv e concentration of 13 nM. In G4F cells lacking MC1-R, agouti is withou t effect. Agouti was also found to induce MC1-R down-regulation with i dentical kinetics and magnitude as alpha-MSH. Thus, the different effe cts of agouti on B16-F1 cells proceed via interaction with MC1-R but a re not exclusively antagonistic. (C) 1996 Academic Press, Inc.