ep-045 and sulotroban

Two-phase thromboxane A2 (TXA2) generation was observed in washed rat platelets stimulated by collagen. One coincided with shape change and the other with aggregation, and both reactions were inhibited by indomethacin. The collagen-induced first phase was not affected by treatment of the platelets with TXA2 receptor antagonist BM13177, while the shape change, the second phase TXA2 generation and aggregation were completely suppressed. U46619, a stable TXA2 mimetic, induced only platelet shape change and not aggregation or endogenous icosanoid mobilization. However, upon addition of U46619 to platelets previously stimulated by collagen in the presence of indomethacin, icosanoids formation was induced together with aggregation. These results suggest that both the collagen-induced initial TXA2 and the occupation of the receptor by collagen might be a trigger for the second-phase TXA2 formation in concert with platelet aggregation.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Collagen; Dose-Response Relationship, Drug; Indomethacin; Kinetics; Phospholipases; Platelet Aggregation; Prostaglandin Endoperoxides, Synthetic; Prostaglandins, Synthetic; Quinacrine; Rats; Receptors, Prostaglandin; Receptors, Thromboxane; Sulfonamides; Thromboxane A2