Soluble endothelin degradation enzyme activities in various rat tissues.
From soluble extract of rat kidney we have previously identified an endothelin degradation enzyme that rapidly and specifically cleaves off the C-terminal tryptophan of endothelin-1, resulting in a peptide that is three orders of magnitude weaker in potency than endothelin-1 in causing smooth muscle contraction. The tissue distribution of this enzyme was examined, and the soluble extracts of rat kidney were found to contain the highest enzyme activity, followed by the spleen and the liver. In contrast, no enzyme activity was detected in the soluble extracts of brain, heart, and lung. The biochemical properties of the partially purified enzyme from kidney were further investigated. The optimal pH of the enzyme was between 5 and 7. The endothelin degrading activity was effectively blocked by thiol protease inhibitors such as benzyloxycarbonyl-Phe-Ala-diazomethyl ketone and p-hydroxymercuribenzoic acid, as well as by phenylmethylsulfonyl fluoride, but not by metalloprotease and other serine protease inhibitors. This enzyme displayed a clear difference in substrate specificity when compared with other thiol proteases such as cathepsin B, cathepsin H, and cathepsin L, known to be present in the kidney. These results suggest that a novel protease with endothelin degrading activity is widely distributed in a number of tissues.
Deng
Y
Y
Research Department, CIBA-GEIGY Corporation, Summit, NJ 07901.
Jeng
A Y
AY
D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D010450:Endopeptidases; D016232:Endothelins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009928:Organ Specificity; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000201:enzymology*; D013379:Substrate Specificity; D014364:Tryptophan / Q000378:metabolism
D016232:Endothelins; D011480:Protease Inhibitors; D014364:Tryptophan; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D056655:Cathepsin H; C534128:Ctsh protein, rat