Metabolism of bradykinin analogs by angiotensin I converting enzyme and carboxypeptidase N.
Bradykinin (BK) analogs such as Lys-Lys-BK, des-Arg9-BK and [Leu8]des-Arg9-BK were poor substrates for angiotensin I converting enzyme (ACE), and analogs containing D-Phe7 residues, or a pseudopeptide C-terminal bond, were completely resistant. However, many of these analogs were metabolized by carboxypeptidase N (CPN) including Lys-Lys-BK, [Tyr8(OMe)]BK and D-Phe7-containing analogs, with Km and Vmax values comparable to those for BK. The only analogs completely resistant to both ACE and CPN were the B2 agonist [Phe8 psi(CH2NH)Arg9]BK, the B2 agonist D-Arg[Hyp3,D-Phe7,Phe8 psi(CH2NH)Arg9]BK, and the B1 agonist [D-Phe8]des-Arg9-BK. These data indicate an important role for plasma CPN and vascular CPN-like activity in the metabolism of the widely used ACE-resistant/D-Phe7-containing antagonists of B2 kinin receptors.
Drapeau
G
G
Department of Physiology, Ohio State University, Columbus 43210.
Chow
A
A
Ward
P E
PE
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D001121:Lysine Carboxypeptidase / Q000097:blood / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D001920:Bradykinin