Differential effects of aspirin and indomethacin on platelet and leukocyte thromboxane A2 formation.
In this study, the in vitro inhibitory effects of aspirin and indomethacin on the arachidonic acid induced thromboxane B2 formation by human leukocytes, are evaluated. The results are compared to those obtained using similarly challenged human washed platelets. Acetylsalicylic acid inhibition, calculated as IC50 by a dose-response curve, is more than ten fold higher for leukocytes vs platelets. In fact, a concentration of aspirin as low as 5 microM almost completely suppresses thromboxane B2 formation by washed platelets, whereas a concentration of 50 microM is necessary to achieve the same inhibition with leukocytes. Indomethacin (0.001-100 microM), incubated with platelet and leukocyte suspensions acts similarly to aspirin. Leukocyte and platelet cyclooxygenases are, therefore, differently affected by both aspirin and indomethacin. These differences may be relevant in the understanding of the wide divergence between the aspirin doses used in thrombosis prevention and in the treatment of inflammatory disease.
D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D013931:Thromboxanes; D013928:Thromboxane A2; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D007213:Indomethacin