Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma.

This report describes a plasmatic, fast-acting, specific inhibitor (antiactivator) of tissue-type plasminogen activator (t-PA) and urokinase (UK). After addition of t-PA to human plasma, biexponential decay of activity occurred. The initial rapid inhibition of t-PA activity (half-life of approximately one minute) was correlated with the formation of a complex of a molecular weight of 110,000, suggesting a molecular weight in the order of 40,000 for the antiactivator. Diisopropylfluorophosphate (DFP)-inactivated t-PA did not form complexes with antiactivator. The second-order rate constant for the interaction of t-PA with antiactivator is in the order of 10(7) mol/L-1 sec-1. In plasma, UK added at low concentrations rapidly formed complexes of a mol wt 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.