The inhibition of cyclo-oxygenase of rabbit platelets by aspirin is prevented by salicylic acid and by phenanthrolines.
Salicylic acid, 1,10- and 1,7-phenanthroline prevented inhibition by aspirin of platelet aggregation and of generation of thromboxane A2 due to arachidonic acid, to the ionophore A21387, to thrombin and to collagen. Dithiothreitol, another drug which prevents aggregation and formation of thromboxane A2, but only reversibly, failed to interfere with the inhibition by aspirin. Irreversible inhibition by indomethacin and by the substrate analogue 5,8,11,14-tetraynoic acid was also unaffected by salicylic acid or by 1,10-phenanthroline, which thus probably exert a specific interaction with the aspirin-binding site. Inactivation of platelet cyclo-oxygenase with arachidonic acid led to inhibition of the formation of thromboxane A2 and of aggregation due to arachidonic acid itself and to collagen, but barely affected aggregation by thrombin, even though generation of thromboxane A2 was blocked. Use of salicylic acid and of reversible inhibitors of cyclo-oxygenase may help to unravel the mechanism of inhibition due to other agents.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000037:antagonists & inhibitors*; D001792:Blood Platelets / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors; D004229:Dithiothreitol / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012459:Salicylates / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism; D013997:Time Factors
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D010618:Phenanthrolines; D012459:Salicylates; D013928:Thromboxane A2; D001241:Aspirin; D004229:Dithiothreitol; D007213:Indomethacin