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

Since endothelin was found to be expressed in epithelial cells as well as in vascular endothelial cells, the functional regulation of melanocytes with endothelin has been actively investigated. In particular, it has been suggested that endothelin may influence pigmentation and depigmentation, which are mediated by melanocytes. In the present study, we investigated the regulation of melanocyte function and tyrosinase expression by endothelin from the point of view of tyrosinase protein expression and enzyme activity. The influence of endothelins on melanocyte function was assessed. Melanocytes showed a dose-dependent increase in cell proliferation with the addition of endothelin-1. When the confluence of melanocytes was cultured with endothelin-1 for 72 h, tyrosinase activity in melanocytes was significantly and dose-dependently decreased. In contrast, there was no significant change with endothelin-3. However, tyrosinase protein expression of melanocytes was significantly and dose-dependently increased by endothelin-1, but endothelin-3 had no effect. Both the suppression of enzyme activity and the enhanced protein expression were regulated by the ETA receptor antagonist, BQ123. In view of these observations, we conclude that endothelin-1-induced tyrosinase is mediated by ETA receptors. 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.