Contributions of various rat plasma peptidases to kinin hydrolysis.
The relative contribution of plasma carboxypeptidase N (kininase I), angiotensin-converting enzyme (ACE) (kininase II), neutral endopeptidase 24.11 (enkephalinase A) and postproline cleaving enzyme to total kininase activity in rat plasma was determined by measuring bradykinin hydrolysis with and without various concentrations of inhibitors of these enzymes. We used DL-2-mercaptomethyl-3-guanidinoethyl-thiopropanoic acid to inhibit kininase I, enalaprilat for ACE, phosphoramidon for neutral endopeptidase 24.11 and N-benzyloxycarbonyl-Pro-prolinal for postproline cleaving enzyme. Bradykinin was added to rat plasma and incubated at 37 degrees C. Kininase activity was evaluated based on the decrease in bradykinin during incubation. Bradykinin was measured by radioimmunoassay, using an antibody that recognizes its carboxyl group. Of the total plasma kininase activity, carboxypeptidase N was responsible for 11.0 +/- 2.5% (N = 5; P less than .05) and ACE for 46.8 +/- 1.5% (N = 5; P less than .001), whereas the contribution of neutral endopeptidase 24.11 and postproline cleaving enzyme turned out to be negligible. Of the kininase activity in rat plasma, 42% could not be explained by any of these four enzymes. We concluded that ACE is responsible for most of the kininase activity in rat plasma; carboxypeptidase N contributes to a slight degree. The fact that 42% of total plasma kininase activity could not be explained by any of the enzymes tested suggests that there are still other kininases in rat plasma which remain to be discovered.
Ishida
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H
Hypertension Research Division, Henry Ford Hospital, Detroit, Michigan.
Scicli
A G
AG
Carretero
O A
OA
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism; D002268:Carboxypeptidases / Q000097:blood*; D006868:Hydrolysis; D007705:Kinins / Q000378:metabolism*; D001121:Lysine Carboxypeptidase / Q000037:antagonists & inhibitors / Q000097:blood*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains
D007705:Kinins; C024626:bradykinin, des-Arg(9)-; C029729:2-mercaptomethyl-3-guanidinoethylthiopropionic acid; D015097:3-Mercaptopropionic Acid; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D001920:Bradykinin