Poststatin, a novel inhibitor of bradykinin-degrading enzymes in rat urine.
Incubation of bradykinin with rat urine resulted in the successive degradation of bradykinin to bradykinin-(1-8), bradykinin-(1-7) and bradykinin-(1-6). In contrast, in rat plasma, bradykinin was degraded via either bradykinin-(1-8) or bradykinin-(1-7) to bradykinin-(1-5). Phosphoramidon (1 mM) partially inhibited the degradation of bradykinin by rat urine, as well as the conversion of bradykinin-(1-7) to bradykinin-(1-6). D,L-2-Mercaptomethyl-3-guanidinoethylthiopropanoic acid (1 mM) and captopril (1 mM) did not have a significant effect on any of the degradation steps in rat urine. In contrast, all of the degradation steps in urine, namely, from bradykinin to bradykinin-(1-8), from bradykinin-(1-8) to bradykinin-(1-7) and from bradykinin-(1-7) to bradykinin-(1-6), were markedly inhibited by poststatin (1 mM), even though this compound was reported originally to be a novel inhibitor of post-proline cleaving enzyme. Poststatin (1 mM) did not inhibit the degradation of bradykinin in rat plasma. These results indicate that poststatin is an effective inhibitor of kinin-degrading enzyme in rat urine.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Shima
C
C
Saito
M
M
Kuribayashi
Y
Y
Katori
M
M
Aoyagi
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004798:Enzymes / Q000652:urine*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000652:urine*; D010446:Peptide Fragments / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004798:Enzymes; D009842:Oligopeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; C071400:poststatin; D001920:Bradykinin