Synergistic actions of paf-acether and sodium arachidonate in human platelet aggregation. 2. Unexpected results after aspirin intake.
The effect of sodium arachidonate and paf-acether on the activation of human platelet rich plasma from volunteers 2.30 to 36 hours after 500 mg of aspirin intake was studied. Concentrations of paf-acether which induce a reversible aggregation in platelet rich plasma (PRP) (0.29-0.029 microM) and concentrations of sodium arachidonate (AA) which don't produce aggregation (0.75-1mM) on the PRP from these volunteers, induced full aggregation when added together. But no cooperation activity was achieved in the 2.30 hours sample. Contrarily to the in vitro studies performed in human normal PRP, ASA (200 micrograms/ml) or indomethacin(12 microM) added to the PRP were unable to suppress the cooperative aggregation effect; neither did apyrase (12U/ml), esculetin (10 microM) or nordihydroguaiaretic acid (0.1 microM) have any action on the activated platelets but the synergistic action is completely suppressed by BW 755C (0.1 mM). TXB2 formation is very low in all these activated samples and insufficient to cause platelet aggregation. These results suggest 2 behaviors of platelets: synergistic activity of paf-acether and exogenous AA in vitro on normal human PRP is mediated mainly through active metabolites of AA formed via cyclooxygenase, as was previously published. When cyclooxygenase is inhibited in vivo by administration of 500 mg ASA, the cooperative effect of agonists is still present but the active aggregating product(s) is probably, formed through a pathway different of that of the cyclooxygenase or lypoxygenase.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000241:Adenosine / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D001081:Apyrase / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D004357:Drug Synergism; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors; D014468:Umbelliferones / Q000494:pharmacology
D001095:Arachidonic Acids; D002396:Catechols; D010972:Platelet Activating Factor; D011720:Pyrazoles; D014468:Umbelliferones; D013929:Thromboxane B2; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D011464:Epoprostenol; D001081:Apyrase; D000241:Adenosine; D001241:Aspirin; C007628:esculetin; D007213:Indomethacin