THROMBIN AND DEXAMETHASONE UPREGULATE EXPRESSION OF ENDOTHELIN-CONVERTING ENZYME-1 IN RAT ENDOTHELIAL CELLS

Endothelin (ET)-1, a potent endothelium-derived vasoconstrictive peptide, is proteolytically processed from an intermediate form (big ET-1) by an endothelin-converting enzyme (ECE)-1. In the present study, we have studied the effects of thrombin, phorbol ester and glucocorticoids on the gene expression and the enzyme activity of ECE in cultured rat endothelial cells (ECs). Both thrombin and tetradecanoylphorbol acetate increased the steady-state levels of ECE-1 mRNA and the enzymatic activity, whose effects were completely abolished by calphostin C, a protein kinase C (PKC) inhibitor. Dexamethasone also upregulated ECE-1 mRNA levels as well as ECE activity. These data suggest that thrombin upregulates ECE-1 gene expression in ECs via PKC-dependent mechanism, and that glucocorticoids have stimulatory effect on the induction of ECE-1.