Studies of angiotensin I converting enzyme: effects of kinins, bacitracin, gamma-aminobutyric and epsilon-aminocaproic acids, and related compounds on substrate binding and catalysis in vitro.
Bradykinin and 22 of its analogs were evaluated for their abilities to inhibit the hydrolysis of [3H]hippurylglycylglycine by purified porcine kidney angiotensin I converting enzyme. The mean inhibitory concentration (IC50) for bradykinin was 1.2 +/- 0.2 X 10(-6) M. Except for Ile-Ser-bradykinin and [Sar4]-bradykinin, none of the kinin analogs were more potent in this regard than bradykinin. Bacitracin, gamma-aminobutyric acid, epsilon-aminocaproic acid, and structurally related compounds were also tested. The IC50 value for bacitracin was 1.9 +/- 0.4 X 10(-4) M, gamma-aminobutyric acid, 83.4 +/- 7.2 mM, and for epsilon-aminocaproic acid, 7.0 +/- 1.4 mM. Compounds were also evaluated for their abilities to prevent 125I-labelled [Tyr1]-kallidin binding to angiotensin I converting enzyme inhibited by EDTA. The IC50 values for bradykinin, bacitracin, gamma-aminobutyric acid, and epsilon-aminocaproic acid were 1.6 +/- 0.3 X 10(-8) M, 2.6 +/- 0.9 X 10(-6) M, greater than 291 mM, and 13.2 +/- 3.9 mM, respectively.
D000614:Aminocaproates / Q000494:pharmacology*; D015119:Aminocaproic Acid / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001414:Bacitracin / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives; D006868:Hydrolysis; D007609:Kallidin / Q000378:metabolism; D007700:Kinetics; D007705:Kinins / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013552:Swine; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000614:Aminocaproates; D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D009842:Oligopeptides; D001414:Bacitracin; C029275:hippuryl-glycyl-glycine; D007609:Kallidin; D005680:gamma-Aminobutyric Acid; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin; D015119:Aminocaproic Acid