The fibrinolytic action of flufenamate and its influence on plasminogen binding to fibrin.
The effects of the synthetic fibrinolytic agent flufenamate were investigated in a purified system made up of bovine fibrin and human plasminogen. The lysis of the fibrin clots was observed after a 12-hour incubation for flufenamate concentrations ranging from 0.25 to 3 mM. Below 0.25 mM and above 3 mM, no lysis occurred, even after a longer incubation. An increase in plasminogen adsorption on the fibrin clot was also observed in the presence of flufenamate. The amount of plasminogen bound was estimated using 125I labelled Glu-plasminogen or Lys-plasminogen, in the presence of a protease inhibitor to avoid the fibrinolysis induced at lytic concentrations of flufenamate. Maximum binding was observed with both types of plasminogen at a flufenamate concentration of 2.5 mM. The binding, relatively fast at the start of incubation, slowed down progressively, but a real plateau was not reached, even after a 6-day incubation. Plasminogen binding was not saturable, suggesting a non-specific binding type. Although Lys-plasminogen binding was always greater than that of Glu-plasminogen, the effect of flufenamate was more pronounced on Glu-plasminogen binding.
D000818:Animals; D002417:Cattle; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005439:Flufenamic Acid / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*
D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C018998:lysyl-plasminogen; D005439:Flufenamic Acid; D005337:Fibrin; D010958:Plasminogen