The relationship between soluble and membranebound endothelin-converting enzyme (ECE) activity with the level of endothelin-1 (ET-1) synthesis was investigated in cultured endothelial cells. Escherichia coli lipopolysaccharide (LPS) was used to stimulate ET-1 synthesis, and brefeldin A, monensin, colchicine or cytochalasin B, which disrupt peptide biosynthetic pathways in a variety of ways, were tested for their ability to modify changes in ET-1 synthesis and ECE levels. LPS increased ET-1 secretion by more than twofold. Levels of soluble ECE activity, but not those of membrane-bound ECE activity, correlated with ET-1 synthesis. These results suggest the soluble ECE activity is likely to play a role in ET-1 biosynthesis.
Address correspondence and reprint requests to Roger Corder, William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, U.K.
© 2000 Lippincott Williams & Wilkins, Inc.