Inhibitory effect of activated protein C on platelet aggregation induced by the prothrombin-converting reaction.
The present study was undertaken to elucidate the effect on platelet aggregation of the prothrombin-converting reaction on platelets with or without activated protein C (APC). A reaction mixture of washed platelets from human individuals, Factor Xa and prothrombin markedly induced platelet aggregation; maximum aggregation rates, 31.3-92.5%, and times to reach to maximum aggregation, 11.6 to 20.1 min. This aggregation was inhibited by the addition of APC with 50% inhibition concentration (IC50) value of 14.4 U/ml. APC also inhibited thrombin generation in the reaction mixture in a dose-dependent manner with IC50 value of 0.96 U/ml. However, APC did not inhibit the thrombin (0.1 CU/ml)-induced platelet aggregation at concentrations of up to 30 U/ml. These findings suggest that APC has no direct inhibitory effect on platelet aggregation and that APC inhibits platelet aggregation through inhibition of thrombin generation.
Komoriya
K
K
Teijin Institute for Bio-medical Research II, Tokyo, Japan.
Inoue
K
K
Takahashi
K
K
Suzuki
K
K
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003374:Coumarins; D015951:Factor Xa / Q000378:metabolism / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D009842:Oligopeptides; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011486:Protein C / Q000378:metabolism / Q000494:pharmacology*; D011516:Prothrombin / Q000378:metabolism* / Q000494:pharmacology; D013917:Thrombin / Q000096:biosynthesis / Q000494:pharmacology
D003374:Coumarins; D005456:Fluorescent Dyes; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D011486:Protein C; C036903:tertiary-butyloxycarbonyl-valyl-prolyl-arginyl-7-amino-4-methylcoumarin; D011516:Prothrombin; D013917:Thrombin; D015951:Factor Xa