DEMONSTRATION OF A FAST-ACTING INHIBITOR OF PLASMINOGEN ACTIVATORS IN HUMAN-PLASMA

Abstract

A plasmatic, fast-acting, specific inhibitor (antiactivator) of tissue-type plasminogen activator (t-PA) and urokinase (UK) is described. After addition of t-PA to human plasma, biexponential decay of activity occurred. The initial rapid inhibition of t-PA activity (half-life of .apprx. 1 min) was correlated with the formation of a complex of a MW of 110,000, suggesting a MW in the order of 40,000 for the antiactivator. Diisopropylflurophosphate (DFP)-inactivated t-PA did not form complexes with antiactivator. The 2nd-order rate constant for the interaction of t-PA with antiactivator is in the order of 107 mol/l-1. In plasma, UK added at low concentrations rapidly formed complexes of a MW of 95,000. Preincubation of the plasma with t-PA prevented complex formation of UK, and vice versa, suggesting that the same inhibitor inactivates both t-PA and UK. After exhaustion of the antiactivator, t-PA and UK formed complexes with .alpha.2-antiplasmin and C1''-inhibitor at a low rate.