Aspirin and dazoxiben as inhibitors of platelet behaviour: modification of their effects by agents that alter cAMP production.
The effects of aspirin and dazoxiben were determined on platelet behaviour in platelet-rich plasma (PRP) from 20 volunteers. Dazoxiben prevented aggregation and the release reaction induced by arachidonic acid (AA) in nine of the samples; in the other eleven aggregation and the release reaction still occurred. Aspirin always prevented aggregation and release but higher concentrations were needed in some of the samples of PRP than with others. When the platelets were sensitive to dazoxiben they were relatively sensitive to aspirin; when they were insensitive to dazoxiben they were relatively insensitive to aspirin. The effects of agents that alter production of cAMP on the sensitivity of platelets to aspirin and dazoxiben were determined. Increasing the intracellular level of cAMP rendered platelets more sensitive to the inhibitory effects of both aspirin and dazoxiben; lowering the level of cAMP made the platelets less sensitive to both agents.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000097:blood
D000067956:Adenylyl Cyclase Inhibitors; D001095:Arachidonic Acids; D007093:Imidazoles; C029166:dazoxiben; C017759:9-(tetrahydro-2-furyl)-adenine; D012701:Serotonin; D011464:Epoprostenol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000225:Adenine; D001241:Aspirin