Platelet Lipoxygenase Inhibitors Attenuate Thrombin- and Thromboxane M imetic-Induced Intracellular Calcium

Platelets metabolize arachidonic acid via cyclooxygenase and lipoxygenase (LO) enzymatic pathways. Although platelets pro-duce large amounts of arachidonic acid metabolites via the LO pathway, little is known regarding the physiological significance of these products. We used three structurally dissimilar LO inhibitors, 5,8,1 1-eicosatriynoic acid (ETI), baicalein and pheni-done, and found that LO inhibition attenuated thrombin- and U4661 9 (a thromboxane mimetic)-induced increases of platelet intracellular calcium ([Ca i in washed human platelets. LO inhibitors also reduced platelet aggregation induced by throm-bin and U46619. The effect of ETI on reducing the thrombin-induced [Ca’ elevation persisted even when cation channels were blocked, suggesting that LO inhibitors modify release of Ca from intracellular stores. Stimulating endogenous LO prod-uct formation potentiated thrombin-induced [Ca’ “] response