Kallikrein Inhibitors in Rat Plasma

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Abstract
The kallikrein inhibitor contents of human and animal plasma were determined with glandular kallikreins [EC 3.4.21.8]. One ml of plasma could inactivate 20–700 kallikrein units (KU). Rat plasma was the most potent and inactivated 230–700 KU. However, no enzyme capable of inactivating kallikrein could be found in this plasma. Two fractions which inhibited hog pancreatic kallikrein, a fraction corresponding to α2-macroglobulin and a fraction which was eluted prior to albumin, were separated from rat plasma by Sephadex G-200 gel filtration. The former inhibitor could inhibit hog pancreatic kallikrein action on Nα-benzoyl-L-arginine ethyl ester (BAEE) as well as in the dog vasodilator assay. The other inhibitor was partially purified from rat plasma. One mg of the preparation inhibited 67 KU and the hydrolysis of 5.8 μimoles/min of BAEE by hog pancreatic kallikrein [EC 3.4.21.8]. The inhibitor also inhibited other glandular and plasma kallikreins, trypsin [EC 3.4.21.4], α-chymotrypsin [EC 3.4.21.1], etc. The optimal pH of the inhibitor was 7.5–8. The inhibitor was unstable below pH 5, and was destroyed by heating at temperature above 60°. The isoelectric point of the inhibitor was determined by Ampholine focusing to be 4.4, and its molecular weight was estimated to be 73,000 by Sephadex G-100 and G-150 nitrations. Several experimental results suggested that this inhibitor differed from α1-antitrypsin.