title: Relationship between soluble intracellular endothelin-converting enzyme and endothelin-1 synthesis: effect of inhibitors of the secretory pathway.
abstract: 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.
authors.affiliation: William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, UK.
authors.forename: R
authors.initials: R
authors.lastname: Corder
authors.forename: N Q
authors.initials: NQ
authors.lastname: Khan
authors.forename: V J
authors.initials: VJ
authors.lastname: Harrison
authors.forename: E G
authors.initials: EG
authors.lastname: Wood
authors.forename: D M
authors.initials: DM
authors.lastname: Lees
authors.forename: S
authors.initials: S
authors.lastname: Barker
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D000072396:Endothelin-Converting Enzymes; D008070:Lipopolysaccharides / Q000494:pharmacology; D008666:Metalloendopeptidases; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D019332:Endothelin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D003078:Colchicine