Effects of metabolized and unmetabolized arachidonate on rat platelet shape change.

Arachidonate (0.12-1.5 mM) initiated a concentration-dependent, saturable shape change of rat platelets suspended in citrated plasma. Interaction of arachidonate with platelets led to the formation of active metabolites that appeared to be the actual inducers of shape change. Among these, prostaglandin endoperoxides rather than thromboxane A2 seemed necessary for shape change. No role of the products of the lipoxygenase pathway could be shown. In the presence of cyclooxygenase and lipoxygenase inhibitors, arachidonate (0.25-0.5 mM) prevented platelet shape change induced by the endoperoxide analog U-46619 but not by other agonists such as ADP or serotonin. Arachidonate acts therefore as both an agonist and an antagonist of platelet shape change. The agonistic effect requires arachidonate metabolism while the antagonistic activity seems to be linked to the fatty acid molecule itself.