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. Poststain (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.