Tyrosinase induction in normal human cultured melanocytes by endothelin-1.

Since endothelin was found to be expressed epithelium as well as vascular enothelium, the functional regulation of various cells with endothelin have been actively investigated. Especially, it is suggested that endothelin may influence pigmentation and depigmentation, which are mediated by melanocytes. In the present study, we investigated the regulation of melanocyte functions and tyrosinase expression by endothelin from the aspects of tyrosinase protein expression and enzyme activity. The influence of endothelins on melanocyte functions was fundamentally assessed. Melanocytes showed a dose-dependent increase in cell proliferation with the addition of endothelin-1. When the confluence melanocytes were cultured with endothelin-1 for 72 hours, the tyrosinase activity in melanocytes was significantly decreased dose-dependently. In contrast, there was no significant change with endothelin-3. However, the tyrosinase protein expression of melanocytes was significantly increased by endothelin-1 dose-dependently, but endothelin-3 had no effect. Either the suppression of tyrosinase activity or the tyrosinase expression was regulated by endothelin-A receptor antagonists (e.g. BQ123). From these observations, endothelin-1-induced tyrosinase was considered to be mediated by endothelin-A receptors. In actuality, however, the reason for the decrease in the specific activity of tyrosinase remains unknown, and our results suggest that another mechanism underlying the activation of tyrosinase is present in addition to the inductive action of endothelin-1 on tyrosinase.