The Inhibitory Effects of Exogenous Arachidonic Acid on Rabbit Platelet Aggregation and the Release Reaction

Although arachidonic acid causes rabbit platelet aggregation and the release of granule contents in suspensions of washed platelets when used in concentrations of approximately 50-300 sM, higher concentrations (500 MM) cause neither aggregation nor release. Suspensions of platelets from rabbits were exposed to arachidonic acid (250 tM) for 1 5 mm, allowed to recover in the presence of PGE1 for 30 mm, washed, and resuspended; in some experiments, the platelets were treated with aspirin before being exposed to arachidonic acid. Aggregation of platelets pretreated with arachidonic acid was inhibited in response to ADP; this effect was greater with the non-aspirin-treated platelets and persisted for at least 4 hr after resuspension. The association of 125l-fibrinogen with the platelets as a result of ADP stimulation was also inhibited. Aggregation and release of granule contents in response to collagen and low concentrations of thrombin was inhibited, but the inhibition could be overcome by higher concentrations. Thrombin induced further release of granule contents from platelets exposed to arachidonic acid without pretreatment with aspirin. Platelets that had been exposed to arachidonic acid, either with or without pretreatment with aspirin, did not aggregate or undergo further release upon stimulation with arachidonic acid after they were washed and resuspended. Inhibition of the lipoxygenase pathway