Comparative Biological Activities of α-MSH Antagonists in Vertebrate Pigment Cells

Abstract

We have previously reported that melatonin was an effective lightening agonist in the teleostSynbranchus marmoratus,the amphibiansRana pipiensandBufo ictericus,and in the lizardAnolis carolinensis.The hormone, previously applied to the preparations, effectively inhibited α-MSH darkening activity in a dose-independent manner, and was also able to reverse MSH-induced darkening. We presently describe the inhibitory effect of the indoleamine on the murine melanoma cell proliferation. Interestingly, the hormone also stimulated tyrosinase activity, with a correlated increase in melanin content. We also demonstrate that in a diverse lizard species,Urosaurus ornatus,the indoleamine was totally ineffective. The competitive MSH antagonistic activity of H-His-d-Arg-Ala-Trp-d-Phe-Lys-NH2has been demonstrated previously inR. pipiensandU. ornatus.Herein, its inhibitory activity is also reported in another lizard species,A. carolinensis.However, this MSH analogue was inactive inS. marmoratus,and in murine melanoma cells. On the other hand, the 7 thru 10 α-MSH fragment, Ac-Phe-Arg-Trp-Gly-NH2, although ineffective inS. marmoratusandR. pipiens,was an α-MSH antagonist inA. carolinensis.Surprisingly, in the melanoma cell line, the MSH fragment exhibited no agonist or antagonist activity, but dramatically potentiated the MSH-induced increase in tyrosinase activity. These data might suggest that the fragment is participating either in the process of facilitation or in positive cooperativity. The present results, taken together with our previously reported data, demonstrate a major interspecies diversity of the MC1 subtype of melanocortin receptor, and point out the relevance of the membrane microenvironment for the final receptor configuration.