Relationship between soluble intracellular endothelin-converting enzyme and endothelin-1 synthesis: effect of inhibitors of the secretory pathway

• Published in: Journal of cardiovascular pharmacology Vol. 36; no. 5 Suppl 1; p. S19
• Main Authors: Corder, R, Khan, N Q, Harrison, V J, Wood, E G, Lees, D M, Barker, S
• Format: Journal Article
• Language: English
• Published: United States 2000
• Subjects: Animals; Aspartic Acid Endopeptidases - metabolism; Cattle; Cells, Cultured; Colchicine - pharmacology; Endothelin-1 - biosynthesis; Endothelin-1 - genetics; Endothelin-Converting Enzymes; Lipopolysaccharides - pharmacology; Metalloendopeptidases; RNA, Messenger - analysis
• DOI: 10.1097/00005344-200036001-00008
• ISSN: 0160-2446

The relationship between soluble and membrane-bound 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.