To elucidate the role of endothelin-1 (ET-1) as an autocrine growth factor for vascular endothelial cells (ECs), we studied the effects of phosphoramidon, an inhibitor of ET-l-converting enzyme, on the production of ET-1-like immunoreactivity (LI),[125 I] ET-1 binding activity, ET B receptor mRNA expression, phosphoinositide breakdown, and DNA synthesis in cultured bovine carotid artery ECs. Phosphoramidon dose-dependently decreased ET-1-LI production but reciprocally increased [125 I] ET-1 binding capacity. ET-1 and ET-3 equipotently inhibited the binding of [125 I] ET-1 only in the presence of phosphoramidon. Northern blot analysis revealed that