Degradation of bradykinin in human urine by carboxypeptidase Y-like exopeptidase and neutral endopeptidase and their inhibition by ebelactone B and phosphoramidon.
Incubation of bradykinin with human urine resulted in a successive degradation of bradykinin-(1-8), bradykinin-(1-7), bradykinin-(1-6), and bradykinin-(1-5). Although D,L-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (100 microM) and captopril (100 microM) did not have any significant effect on bradykinin degradation in human urine, the neutral endopeptidase inhibitor phosphoramidon (100 microM), a carboxypeptidase Y-like exopeptidase inhibitor ebelactone B (100 microM), and o-phenanthroline (100 microM) significantly inhibited bradykinin degradation by 36%, 38% and 48% respectively. The combination of phosphoramidon and ebelactone B completely (by 95%) inhibited bradykinin degradation in human urine. At pH 5, bradykinin degradation was performed by carboxypeptidase Y-like exopeptidase; at pH 7, this degradation was performed by neutral endopeptidase in addition to carboxypeptidase Y-like exopeptidase. From these results, it can be concluded that carboxypeptidase Y-like exopeptidase and/or neutral endopeptidase certainly have a role in kinin degradation in human urine under neutral and acid pH conditions.
Saito
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Majima
M
M
Katori
M
M
Sanjou
Y
Y
Suyama
I
I
Shiokawa
H
H
Koshiba
K
K
Aoyagi
T
T
D000328:Adult; D000368:Aged; D001920:Bradykinin / Q000652:urine*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043402:Cathepsin A; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*
D006020:Glycopeptides; D007783:Lactones; D011480:Protease Inhibitors; C030795:ebelactone B; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A; D015260:Neprilysin; D001920:Bradykinin; C008890:phosphoramidon