Characterization of endothelin converting enzyme in rat lung.
An enzyme activity which converts human big endothelin (1-38) to endothelin (1-21) and a C-terminal fragment (CTF, 22-38) was identified in a plasma membrane fraction prepared from rat lung. The conversion activity was optimal at pH 4.0, was inhibited by Pepstatin-A (IC50 = 20 nM), but was not affected by TLCK, Aprotinin, PMSF, E-64, Bestatin, Phosphoramidon or Thiorphan at 40 microM. Metal ions activated the activity by 1.5 - 2.5 fold in the order of Mn+2 greater than Zn+2 = Ca+2 greater than Ba+2. These data suggest that a Pepstatin-A inhibitable, metal ion related aspartic protease may be involved in the conversion of big endothelin to endothelin in rat lung.
Wu-Wong
J R
JR
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064.
Budzik
G P
GP
Devine
E M
EM
Opgenorth
T J
TJ
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D002413:Cations, Divalent; D002462:Cell Membrane / Q000201:enzymology; D002712:Chlorides; D002851:Chromatography, High Pressure Liquid; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D008666:Metalloendopeptidases; D051381:Rats
D002413:Cations, Divalent; D002712:Chlorides; D016232:Endothelins; D017895:Manganese Compounds; D008345:Manganese; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C025340:manganese chloride