Inhibition of human platelet and neutrophil function by piriprost (U-60,257).
Platelets and neutrophils are important in determining the extent of myocardial injury following coronary occlusion. The detrimental effects of these blood elements are mediated in part via release of arachidonate metabolites and oxidative species. A new selective inhibitor of leukotriene formation, piriprost (U-60,257), has been observed to decrease both neutrophil accumulation in the myocardium and infarct size following coronary ligation in experimental animals. Since piriprost may have clinical use, we examined its effects on human platelet and neutrophil functions. This compound was found to exert potent inhibitory effects on epinephrine-induced human platelet aggregation and TXA2 biosynthesis (IC50 0.04 microM). Piriprost also inhibited human neutrophil chemotaxis, oxidative species release, aggregation, and LTB4 synthesis with IC50 of 0.1, 0.04, 10 and 14 microM, respectively. Thus, piriprost inhibits a variety of human platelet and neutrophil functions. Because of its suppressive effects on human platelet and neutrophil functions and protective effects in experimental myocardial infarction, this agent may have clinical applications.
D001792:Blood Platelets / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects*; D010084:Oxidation-Reduction; D010974:Platelet Aggregation / Q000187:drug effects; D013189:SRS-A / Q000037:antagonists & inhibitors*
D013189:SRS-A; D000001:Calcimycin; D011464:Epoprostenol; C035296:piriprost; D004837:Epinephrine