Metabolism of bradykinin analogs by angiotensin I converting enzyme and carboxypeptidase N. |
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Authors: | G Drapeau A Chow P E Ward |
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Institution: | Department of Physiology, Ohio State University, Columbus 43210. |
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Abstract: | 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-ArgHyp3,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. |
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