Inhibition of angiotensin-converting enzyme by des-Leu10-angiotensin I: a potential mechanism of endogenous angiotensin-converting enzyme regulation.
Des-Leu10-angiotensin I is a nonapeptide generated from angiotensin I by the action of carboxypeptidase-like activities residing in the human platelet and mast cell. This nonapeptide was found to inhibit rabbit lung angiotensin-converting enzyme (peptidyl-dipeptide hydrolase, EC 3.4.15.1) with a Ki of 3.1 X 10(-7) M. The mechanism of inhibition was competitive. Inhibition of human serum angiotensin-converting enzyme by des-Leu10-angiotensin I was comparable in magnitude to inhibition by bradykinin and angiotensin III. These results suggest that limited proteolysis of angiotensin I by cells resident in vascular tissue may result in the generation of an endogenous inhibitor of angiotensin-converting enzyme. Such pathways may play roles in controlling levels of vasoactive peptides at local vascular sites.
D000803:Angiotensin I / Q000031:analogs & derivatives / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; C045857:angiotensin I, des-Leu(10)-; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin