A stable metabolite, Arg-Pro-Pro-Gly-Phe, of bradykinin in the degradation pathway in human plasma.
Degradation of bradykinin (BK) in human plasma was investigated by searching for a stable metabolite as a marker of kinin release in vivo. BK, incubated with diluted plasma, was degraded to des-Arg9-BK (des-9-BK), des-Phe8-Arg9-BK (des-8,9-BK) and Arg-Pro-Pro-Gly-Phe ([1-5]BK). Des-9-BK was degraded to [1-5]BK without an increase in des-8,9-BK, and des-8,9-BK was also degraded to [1-5]BK. D,L-2-Mercaptomethyl-3-guanidinoethyl-thiopropanoic acid inhibited the formation of des-9-BK from BK, whereas captopril inhibited the formation of des-8,9-BK from BK as well as that of [1-5]BK from des-9-BK or des-8,9-BK. The half lives of BK, des-9-BK, des-8,9-BK and [1-5]BK under the present experimental conditions were 60 min, 90 min, 14 min and 4.2 hr, respectively. Among the metabolites, [1-5]BK was the most stable one and may be used as a marker for BK production in vivo.
Shima
C
C
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Majima
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Katori
M
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D000328:Adult; D000595:Amino Acid Sequence; D001920:Bradykinin / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood*
D009842:Oligopeptides; D010446:Peptide Fragments; C024626:bradykinin, des-Arg(9)-; C050809:bradykinin, des-Phe(8)-des-Arg(9)-; C079000:bradykinin (1-5); C079001:arginyl-prolyl-proline; D002216:Captopril; D001920:Bradykinin