12-HETE INHIBITS THE BINDING OF PGH2 TXA2 RECEPTOR LIGANDS IN HUMAN PLATELETS

12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), the end-lipoxygenase product of arachidonic acid in platelets has been previously shown to prevent PGH2/TxA2-induced aggregation. From the present study, we show that 12-HETE inhibits the binding of [I-125]-PTA-OH, a thromboxane antagonist, to platelet membranes with an IC50 of 8-mu-M. This value is in accordance with previously reported 12-HETE concentrations required to prevent the aggregation induced by TxA2 mimetics, the methano analogues of PGH2, U44069 and U46619. When [H-3]-U44069 was used as a thromboxane agonist to label intact platelets, 12-HETE also inhibited its binding. We conclude that part of the inhibitory effect of 12-HETE on PGH2/TxA2-induced aggregation might be the result of interacting with PGH2/TxA2 receptor sites.