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.
D000328:Adult; D004791:Enzyme Inhibitors / Q000097:blood; D005260:Female; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D015849:Plasminogen Inactivators; D007531:Isoflurophate; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator