Synergistic actions of PAF-acether and sodium arachidonate in human platelet aggregation. 1. Studies in normal human platelet rich plasma.
The effect of sodium arachidonate and paf-acether in the activation of human platelet was studied. Concentrations of paf-acether which induced a reversible aggregation in normal human platelet rich plasma (0.029-0.0029 microM) and subthreshold concentrations of sodium arachidonate (0.25-0.35 mM), produced full aggregation when added together. Pre-exposition of platelets to paf-acether that renders them insensitive to paf-acether supresed the synergism. With full aggregation a markedly increase of thromboxane synthesis was detected by RIA. In vitro addition of aspirin (200 micrograms/ml) or indomethacin (12 microM) prevented aggregation and thromboxane formation by the joint action of sodium arachidonate plus paf-acether. Specific inhibition of 12-lipoxygenase by esculetin (10 microM) did not affect the synergistic action of paf-ace-ther and sodium arachidonate. These findings suggest that synergism between both agonists is mediated by active derivatives of arachidonic acid via cyclooxygenase.
D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors
D001095:Arachidonic Acids; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D013929:Thromboxane B2; D001241:Aspirin