title: Inhibitory effects of beraprost on platelet aggregation: comparative study utilizing two methods of aggregometry.
abstract: We evaluated the inhibitory effects of beraprost, a stable prostacyclin analogue, on platelet aggregation, assessed by two methods of platelet aggregometry. The conventional aggregometry detects changes in light transmission (LT) of a platelet suspension, and a recently developed aggregometry based upon a particle counting principle detects light scattering (LS) generated by platelet aggregates. Since LS is more sensitive than LT in detecting platelet aggregates of small size, the minimal concentrations of agonists (ADP, epinephrine, collagen, and U46619) to induce detectable aggregate formation were consistently lower with LS (1/2 to 1/6) than with LT. The effects of beraprost were evaluated on platelet aggregation induced by the optimal concentrations of agonists thus determined for each sample. The IC50 values of beraprost on platelet aggregation, as assessed by LS, were 1/2 to 1/10 of those assessed by LT. In suppressing platelet aggregation assessed by LS, beraprost was especially potent with IC50 of 0.2-0.5 nM when platelets were activated by U46619, a thromboxane A2 analogue, or low concentrations of collagen which activates platelets through thromboxane A2 production. The IC50 values were 2-5 nM with ADP and epinephrine, which induce the formation of small aggregates independently of thromboxane A2 production. These findings suggest that LS can detect inhibitory effects of lower concentrations of antiplatelet agents, since it detects the formation of small aggregates induced by agonists in the lower concentration range than LT. It is also suggested that beraprost potently inhibits thromboxane A2-elicited initial signal transduction pathway, reflected by the formation of small aggregates.
authors.affiliation: Department of Clinical and Laboratory Medicine, Yamanashi Medical University, Nakakoma, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Yatomi
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: Y
authors.initials: Y
authors.lastname: Ozaki
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL / Q000097:blood; D008722:Methods; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count / Q000379:methods; D011493:Protein Kinase C / Q000494:pharmacology; D012542:Scattering, Radiation; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D010975:Platelet Aggregation Inhibitors; D014662:Vasoconstrictor Agents; C048081:beraprost; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D002784:Cholesterol; D011464:Epoprostenol; D011493:Protein Kinase C; D004837:Epinephrine