Potent inhibition of angiotensin-converting enzyme by [des-Pro3]-bradykinin or "converstatin" in comparison with Captopril.
The mechanism of bradykinin-potentiating activity of [des-Proline3]-bradykinin, a kinin originally generated from human plasma protein by trypsin, was studied in terms of its inhibitory actions on angiotensin-converting enzyme and kininase II prepared from rat lung. The results were compared with those obtained with Captopril. [Des-Pro3]-bradykinin was found to have a potent inhibitory action against angiotensin-converting enzyme with a K1 of 4.5 X 10(-12) M, which is approximately 7 times more potent than Captopril. It was also inhibitory to kininase II with a Ki of 4 X 10(-11) M, which is approximately 2,300-fold more potent than Captopril. The pattern of inhibition was purely competitive with increased apparent Km but no change in apparent Vmax for both angiotensin-converting enzyme and kininase II. This is in contrast to Captopril, which showed a mixed competitive and non-competitive type of inhibition with increased apparent Km and decreased Vmax for both enzymes. Such a potent inhibitory activity of [des-Pro3]-bradykinin or Arg-Pro-Gly-Phe-Ser-Pro-Phe-Arg is noteworthy, and accordingly we propose the name "converstatin" for this peptide.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001667:Binding, Competitive; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; C047830:bradykinin, des-Pro(3)-; D002216:Captopril; D001920:Bradykinin