title: Conversion of big endothelin isopeptides to mature endothelin isopeptides by cultured bovine endothelial cells.
abstract: Both the soluble and membrane fractions prepared from cultured bovine endothelial cells (ECs) possessed the converting activities to metabolize big endothelin-1 (big ET-1) to endothelin-1 (ET-1) at neutral pH. Metal chelators inhibited the activities of both fractions, whereas phosphoramidon, a metalloprotease inhibitor, strongly inhibited only the activity of the membrane fraction. Phosphoramidon reduced the secretion of ET-1 and concomitantly enhanced the release of big ET-1 from cultured ECs. The incubations of big ET-1, big ET-2, and big ET-3 with cultured ECs resulted in their conversions to mature ETs. Phosphoramidon also abolished these conversions. These results indicate that vascular endothelium can convert not only endogenous big ET-1 but also exogenous big ET isopeptides to their mature ETs through a phosphoramidon-sensitive neutral metalloprotease.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohnaka
authors.forename: R
authors.initials: R
authors.lastname: Takayanagi
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.forename: H
authors.initials: H
authors.lastname: Nawata
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism*; D004727:Endothelium / Q000201:enzymology / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008666:Metalloendopeptidases; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011480:Protease Inhibitors; D011498:Protein Precursors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon