D-Phe7-substituted peptide bradykinin antagonists are not substrates for kininase II

Abstract The bradykinin receptor antagonists [D-Phe 7 ]bradykinin, D-Arg[Hyp 3 ,D-Phe 7 ]bradykinin and D-Arg[Hyp 3 ,Thi 5,8 ,D-Phe 7 ]bradykinin were tested for their ability to serve as substrates for kininase II (angiotensin converting enzyme) purified from rabbit lung. By HPLC, the peptides were not measurably degraded over 30 minutes. Under identical conditions, bradykinin was completely degraded to bradykinin (1–7). When hippuryl-His-Leu was used as a substrate for kininase II, the D-Phe 7 -substituted bradykinins acted as weak noncompetitive inhibitors. While the peptides were poor substrates for kininase II, they were short-lived when injected intravenously. D-Arg[Hyp 3 ,D-Phe 7 ]bradykinin was completely degraded to small fragments in less than 2 minutes. In diluted serum in vitro, a single product was observed with elution consistent with loss of arginine, suggestive of metabolism by kininase I.