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

• Published in: Canadian journal of physiology and pharmacology Vol. 64; no. 1; p. 50
• Main Authors: Odya, C E, Wilgis, F P
• Format: Journal Article
• Language: English
• Published: Canada 01-01-1986
• Subjects: Aminocaproates - pharmacology; Aminocaproic Acid - pharmacology; Angiotensin-Converting Enzyme Inhibitors; Animals; Bacitracin - pharmacology; Bradykinin - analogs & derivatives; gamma-Aminobutyric Acid - pharmacology; Hydrolysis; Kallidin - metabolism; Kinetics; Kinins - pharmacology; Oligopeptides - metabolism; Peptidyl-Dipeptidase A - metabolism; Swine
• ISSN: 0008-4212
• DOI: 10.1139/y86-007

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.