Role of phosphoinositide 3-kinase in adhesion of platelets to fibrinogen stimulated by cancer procoagulant.
Cancer procoagulant, cysteine proteinase (CP; EC 3.4.22.26) activates factor X and functions in the absence of factor VII. CP may also change the platelet function. It induces an increase of platelet adhesion to collagen and fibrinogen. Using wortmannin--the inhibitor of phosphoinositide 3-kinase (PI 3-K)--we studied the role of this enzyme in the action of cancer procoagulant on blood platelet adhesion in vitro. Wortmannin (25, 50 and 100 nM, 30 min, 37 degrees C) caused a reduction of platelet adhesion to fibrinogen (P<0.01) when blood platelets were stimulated by both 0.2 U/ml thrombin (IC(50)approximately 75 nM) and by 1 microM ADP (IC(50)approximately 60 nM). We observed that after CP treatment the adhesion of thrombin-activated and ADP-stimulated platelets to fibrinogen was augmented. The potentiated by CP adhesion of activated platelets to fibrinogen was reduced after preincubation of platelets with wortmannin (50 nM, 30 min, 37 degrees C). We conclude that in adhesion of platelets to fibrinogen stimulated by CP PI 3-K take place.
Olas
B
B
Department of General Biochemistry, Institute of Biochemistry, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland. olasb@taxus.biol.uni.lodz.pl
Wachowicz
B
B
Mielicki
W P
WP
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism*; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D013552:Swine; D013917:Thrombin / Q000494:pharmacology; D000077191:Wortmannin
D000244:Adenosine Diphosphate; D000730:Androstadienes; D003546:Cysteine Endopeptidases; D005340:Fibrinogen; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013917:Thrombin; D000077191:Wortmannin; C030910:cancer procoagulant