kallidin and hippuryl-glycyl-glycine

Angiotensin I converting enzyme (ACE) and kininase activities were measured in various segments of the rabbit nephron. ACE was determined with tritiated hippuryl-glycylglycine as substrate. Lysyl-bradykinin (LBK) hydrolysis (kininase activity) was measured by radioimmunoassay. ACE was only found in the glomerulus and in the two parts of proximal tubule: the convoluted proximal tubule and the pars recta (PR). It was distributed along a concentration gradient which increased from the glomerulus to PR. Kininase activity was found in both proximal and distal parts of the nephron. Besides intense LBK-hydrolyzing activity in the proximal tubule, a kininase activity was also found in the medullary collecting tubule (MCT). Kininase activity in the glomerulus and the proximal tubule was completely inhibited by chelating agents. Captopril inhibited this activity only in the PR and at high concentrations (above 10(-7) M). These results indicate that several types of enzymes other than ACE hydrolyze kinins in the glomerulus and in the proximal tubule. The contribution of ACE to kinin hydrolysis appears only minimal. The kininase activity found in MCT was different from ACE and other proximal tubule kininases because it was not inhibited by chelating agents. This kininase may play a physiological role in inactivating the kinins formed by kallikrein at or beyond the connecting tubule.

Topics: Animals; Captopril; Edetic Acid; Hydrolysis; Kallidin; Kidney Glomerulus; Kidney Tubules, Collecting; Kidney Tubules, Proximal; Kinins; Male; Microbial Collagenase; Nephrons; Oligopeptides; Peptidyl-Dipeptidase A; Phenanthrolines; Rabbits; Tissue Distribution

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.

Topics: Aminocaproates; Aminocaproic Acid; Angiotensin-Converting Enzyme Inhibitors; Animals; Bacitracin; Bradykinin; gamma-Aminobutyric Acid; Hydrolysis; Kallidin; Kinetics; Kinins; Oligopeptides; Peptidyl-Dipeptidase A; Swine