Search

Tissue-type plasminogen activator (rt-PA) and prourokinase (rscu-PA) have been tested with respect to the influence of amyloid beta peptides on plasminogen activation which was monitored by cleavage of the chromogenic plasmin substrate S-2251. It was shown that rt-PA is stimulated by amyloid beta peptides at concentrations of 10 micrograms/ml in contrast to prourokinase, which does not alter its catalytic properties in presence of amyloid beta peptides. The stimulation of rt-PA can be inhibited by tranexamic acid indicating a molecular mode of stimulation similar to the fibrin mediated stimulation of rt-PA.

The mode of interaction between recombinant tissue-type plasminogen activator (r-t-PA) and recombinant single-chain urokinase-type plasminogen activator (r-scu-PA) has been investigated in in vivo experiments. 125J-fibrin-labeled clots were embolized via a jugular vein into the lungs of anesthetized rabbits. In saline-treated control rabbits the spontaneous lysis, shown as decrease in radioactivity of the retrieved clots, amounted to 10.4 +/- 1.4% at 255 min after the pulmonary embolization. r-t-PA (0.464 - 4.64 micrograms/kg.min) and r-scu-PA (4.64 - 46.4 microns/kg.min), infused for 60 min, produced dose-dependent lytic effects to a similar extent (maximum lysis rate 53.9 +/- 5.8 and 55.4 +/- 7.2%, resp.). When various ratios of submaximal doses of r-t-PA and r-scu-PA were combined the lytic effects of these combinations were not higher than the calculated summation of the lysis rates by the single components. The fractional dose-response curves of r-t-PA and r-scu-PA and the combination of them, fitted by linear regression analysis, are overlaying each other. The results indicate that r-t-PA and r-scu-PA produce in vivo lysis in rabbits with pulmonary embolized clots in a purely additive manner.