Possible involvement of angiotensin I-converting enzyme in the inactivation of bradykinin by intact macrophages.
As intact macrophages inactivated bradykinin, the subcellular localization of the bradykinin-inactivating activity was studied using guinea-pig macrophages. The bradykinin-inactivating activity was found to be present in membrane and cytosol fractions but not in granular and nuclear fractions. The bradykinin-inactivating activity of the membrane fraction was inhibited by captopril, a specific inhibitor of angiotensin I-converting enzyme, whereas that of the cytosol fraction was hardly inhibited by various proteinase inhibitors used. Angiotensin I-converting enzyme activity was located predominantly in the membrane fraction and its activity was inhibited by captopril. Angiotensin I-converting enzyme activity measured with a synthetic substrate was competitively inhibited by bradykinin, suggesting that bradykinin is a possible substrate for macrophage angiotensin I-converting enzyme. When macrophages were modified chemically by diazotized sulfanilic acid, a poorly permeant reagent, both the bradykinin-inactivating activity and the angiotensin I-converting enzyme activity of macrophages decreased significantly without any inhibition of the cytosol bradykinin-inactivating activity. These findings seem to suggest that the angiotensin I-converting enzyme would be responsible for the inactivation of bradykinin in intact macrophages.
D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004492:Edetic Acid / Q000494:pharmacology; D010450:Endopeptidases / Q000502:physiology; D005033:Ethylmaleimide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000494:pharmacology; D012697:Serine Endopeptidases
D000809:Angiotensins; D011480:Protease Inhibitors; D007531:Isoflurophate; D004492:Edetic Acid; D002216:Captopril; D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D005033:Ethylmaleimide; D001920:Bradykinin