Phosphoramidon inhibits the intracellular conversion of big endothelin-1 to endothelin-1 in cultured endothelial cells.
Effects of various protease inhibitors on the conversion of big endothelin (ET)-1 to ET-1 in cultured endothelial cells were analyzed. A metal protease inhibitor, phosphoramidon, decreases the amount of ET-1 and increase that of big ET-1 released. This effect is dose-dependent and not nonspecific. When the contents of ET-1 and big ET-1 in the cells after culturing in the medium with or without phosphoramidon were measured, the ratio of ET-1: big ET-1 in the cells was 3.3 : 1 and phosphoramidon inverted the ratio in the cells to 1 : 3.5. These data strongly suggest that a phosphoramidon-sensitive protease converts big ET-1 to mature ET-1 intracellularly.
Sawamura
T
T
Department of Biochemistry, University of Tsukuba, Ibaraki, Japan.
Kasuya
Y
Y
Matsushita
Y
Y
Suzuki
N
N
Shinmi
O
O
Kishi
N
N
Sugita
Y
Y
Yanagisawa
M
M
Goto
K
K
Masaki
T
T
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019332:Endothelin-1; D016232:Endothelins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology*; D007700:Kinetics; D011480:Protease Inhibitors / Q000494:pharmacology*; D011498:Protein Precursors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011480:Protease Inhibitors; D011498:Protein Precursors; C008890:phosphoramidon