B16 흑색종세포에서 싸이클로스포린 A에 의한 멜라닌 합성 촉진효과에 미치는 칼슘-활성 염소 통로의 역할

Role of Ca2+-activated Cl− Channels in the Stimulation of Melanin Synthesis Induced by Cyclosporin A in B16 Melanoma Cells

The mechanism of melanogenesis induced by cyclosporin A (CsA) was investigated in B16 melanoma cells. CsA stimulated the production of melanin in a dose-dependent manner in the cells. In addition, CsA increased intracellular Ca2+ concentration in a dose-related fashion. Treatment with BAPTA/AM, an intracellular Ca2+ chelator significantly inhibited the CsA-induced intracellular melanin synthesis. CsA profoundly induced Cl- efflux, which was significantly blocked by niflumic acid (NFA) and flufenamic acid (FFA), specific and nonspecific inhibitors of Ca2+-activated Cl− channels (CaCCs), respectively. Furthermore, these inhibitors of CaCCs significantly inhibited the CsA-induced stimulation of melanin synthesis. Taken together, these results suggest that the activation of CaCCs may play an important role in the CsA-induced stimulation of melanin synthesis in B16 cells. These results further suggest that CaCCs may be a good target for the management of hyperpigmentation of the skin reported in the patients treated with CsA.