A comparison of the plasma kinin forming enzymes in urine; kallikrein and urokinase

The experiments of the present paper show that urine contains two enzymes capable of forming plasma kinin; one of these enzymes acts quickly and is probably identical with kallikrein, the other acts more slowly and is probably identical with urokinase. Kallikrein is the name given by Frey & Kraut (1928) to a non-dialysable depressor substance obtained from urine. This was later shown to be an enzyme capable of acting on plasma proteins to form a vasodilator and smooth-muscle-stimulating polypeptide; this plasma kinin was originally called substance DK (Werle, 1937) and later kallidin (Werle & Berek, 1950). Urokinase is the name given by Sobel, Mohler, Jones, Dowdy & Guest (1952) to an activator of plasminogen, the precursor of the proteolytic enzyme plasmin (Astrup & Sterndorff, 1952). Subsequent work by Lewis & Work (1957) and Lewis (1958, 1959) has shown that plasmin and its activators form a plasma kinin when incubated with the pseudoglobulin fraction of plasma. Urokinase should therefore form plasma kinin by first activating plasminogen. The question thus arose whether urinary kallikrein and urokinase were identical, both forming kinins by first activating plasminogen. The results show first a distinct difference in the rate of plasma kinin formation with the two enzymes. Secondly, the urokinase was weight-for-weight 300 times more potent in activating plasminogen, whereas the kallikrein was 40-50 times more potent in producing vasodilatation and about seven times more potent in contracting the dog's ileum.