YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

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

Melanocortin-1 수용체 길항제의 배양된 인간 멜라노사이트에 대한 효과

  • 이상화 (LG생활건강기술연구원) ;
  • 장윤희 (LG생활건강기술연구원) ;
  • 이설훈 (LG생활건강기술연구원) ;
  • 이증훈 (충남대학교 의과대학 의학과 피부과학교실)
  • Received : 2014.01.14
  • Accepted : 2014.01.24
  • Published : 2014.02.28
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Abstract

We have developed 8 peptide derivatives as potential MC1R antagonists and their inhibitory effects on ${\alpha}$-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-$(Lys)_6NH_2$ (P 6) and 5-phenylvaleric acid-(D)His-Arg-Trp-$(Lys)_9NH_2$ (P 7) were selected for further studies. In ${\alpha}$-MSH depleted NHM cells, we have found that the treatment with 1 ${\mu}M$ of these two peptide derivatives, P 6 and P 7, inhibited the cell proliferation induced by the addition of 1 nM ${\alpha}$- MSH by 70% and 72%, respectively. In NHM cells without previous ${\alpha}$-MSH depletion, 1 ${\mu}M$ treatment in the presence of 10 nM ${\alpha}$-MSH resulted in 70% (P 6) and 80% (P 7) decrease in cell growth and 64% (P 6) and 71% (P 7) reduction in melanin 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 ${\alpha}$-MSH. In conclusion, our data suggest that the peptide derivatives reported in this study, 5-phenylvaleric acid-(D)His-Arg-Trp-$(Lys)_6NH_2$ (P 6) and 5-phenylvaleric acid-(D)His- Arg-Trp-$(Lys)_9NH_2$ (P 7) strongly antagonize ${\alpha}$-MSH, inhibit cell proliferation and melanin synthesis, and lower the intracellular cAMP concentration, hence have a promising potential as a novel skin lightening agent.

Keywords

References

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