The fast-acting inhibitor of tissue-type plasminogen activator in plasma is also the primary plasma inhibitor of urokinase.
We have compared the ability of a plasminogen activator inhibitor (PA-inhibitor) in human plasma, to form complexes with radioiodinated tissue-type plasminogen activator (t-PA) and high molecular weight urokinase (HMr-UK). Addition of 125I-t-PA (final concentration 10 IU/ml) or of 125I-HMr-UK (2 IU/ml) to a plasma containing 33 U/ml of PA-inhibitor resulted in the rapid formation of a 110,000 Mr complex of 125I-t-PA or a 95,000 Mr complex of 125I-HMr-UK with PA-inhibitor. Upon prolonged incubation of the plasma with 125I-HMr-UK a secondary complex of a Mr of 88,000 was observed, which probably derives from limited degradation of the 95,000 complex. Preincubation of the plasma with unlabelled t-PA, HMr-UK or LMr-UK at higher concentrations prevented the subsequent formation of complexes between radiolabelled PAs and the PA-inhibitor. These results thus demonstrate that t-PA and UK form complexes with the same PA-inhibitor. The rate of complex formation of 125I-t-PA or of 125I-HMr-UK with the plasma PA-inhibitor was similar (second order rate constant of association with PA-inhibitor in the order of 10(7) M-1s-1).
D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008970:Molecular Weight; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000097:blood
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator