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 [125I]-PTA-OH, a thromboxane antagonist, to platelet membranes with an IC50 of 8 microM. 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 [3H]-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.
Fonlupt
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INSERM U205, Chimie Biologique-INSA B406, Villeurbanne, France.
Croset
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Lagarde
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D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003864:Depression, Chemical; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000096:biosynthesis; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000378:metabolism; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D006893:Hydroxyeicosatetraenoic Acids; D007295:Inositol Phosphates; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D044262:Prostaglandin H2; C028429:U 44069; D013928:Thromboxane A2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C046957:I-PTA-OH