Phosphoramidon inhibits the intracellular conversion of big endothelin-1 to endothelin-1 in cultured endothelial cells

Biochem Biophys Res Commun. 1991 Jan 31;174(2):779-84. doi: 10.1016/0006-291x(91)91485-u.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Endothelin-1
  • Endothelins / genetics*
  • Endothelins / isolation & purification
  • Endothelins / metabolism*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Glycopeptides / pharmacology*
  • Kinetics
  • Protease Inhibitors / pharmacology*
  • Protein Precursors / genetics
  • Protein Precursors / isolation & purification
  • Protein Precursors / metabolism*
  • Protein Processing, Post-Translational / drug effects*

Substances

  • Endothelin-1
  • Endothelins
  • Glycopeptides
  • Protease Inhibitors
  • Protein Precursors
  • phosphoramidon