Studies of endothelin-converting enzyme in bovine endothelial cells and vascular smooth-muscle cells: further characterization of the biosynthetic process.

Endothelin-1 (ET-1) is synthesized by a number of cell types, including endothelial, epithelial, and smooth muscle cells. Initial biosynthesis occurs as a protein precursor, preproendothelin-1 (preproET-1). This is processed intracellularly to the inactive intermediate big ET-1, which is hydrolyzed by endothelin-converting enzyme (ECE) to generate ET-1, but the precise identity of the physiologically relevant ECE has yet to be confirmed. Although ET-1 is synthesized in the constitutive secretory pathway, many features of the selective processing of proET-1 are comparable to those of peptide hormones. We describe here experimental investigations aimed at defining the regulation of ET-1 synthesis and its relationship to the biosynthesis of ECE.