Melanocortin-1 수용체 길항제의 배양된 인간 멜라노사이트에 대한 효과

Effects of Potential Melanocortin-1 Receptor Antagonists on Cultured Normal Human Melanocytes

We have developed 8 peptide derivatives as potential MC1R antagonists and their inhibitory effects on α-MSH induced cell growth in cultured normal human melanocytes (NHM) were investigated. From these experiments, the two most potent peptide derivatives, 5-phenylvaleric acid-(D)His-Arg-Trp-(Lys)6NH2 (P 6) and 5-phenylvaleric acid-(D)His-Arg-Trp-(Lys)9NH2 (P 7) were selected for further studies. In α-MSH depleted NHM cells, we have found that the treatment with 1 µM of these two peptide derivatives, P 6 and P 7, inhibited the cell proliferation induced by the addition of 1 nM α-MSH by 70% and 72%, respectively. In NHM cells without previous α-MSH depletion, 1 µM treatment in the presence of 10 nM α-MSH resulted in 70% (P 6) and 80% (P 7) decrease in cell growth and 64% (P 6) and 71% (P 7) reduction in mel-anin synthesis, respectively. The peptide derivatives P 6 and P 7 were proved to have no apparent cytotoxicity and inhibited the elevation of intracellular cAMP concentration triggered by α-MSH. In conclusion, our data suggest that the peptide derivatives reported in this study, 5-phenylvaleric acid-(D)His-Arg-Trp-(Lys)6NH2 (P 6) and 5-phenylvaleric acid-(D)His-Arg-Trp-(Lys)9NH2 (P 7) strongly antagonize α-MSH, inhibit cell proliferation and melanin synthesis, and lower the intra-cellular cAMP concentration, hence have a promising potential as a novel skin lightening agent.