Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
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Blood Platelets / drug effects*
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Blood Platelets / metabolism
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Depression, Chemical
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Humans
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Hydroxyeicosatetraenoic Acids / pharmacology*
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Inositol Phosphates / biosynthesis
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Platelet Aggregation / drug effects
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Platelet Aggregation Inhibitors / pharmacology*
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Prostaglandin Endoperoxides, Synthetic / antagonists & inhibitors
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Prostaglandin Endoperoxides, Synthetic / metabolism*
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Prostaglandin Endoperoxides, Synthetic / pharmacology
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Prostaglandin H2
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Prostaglandins H / antagonists & inhibitors
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Prostaglandins H / metabolism*
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Receptors, Prostaglandin / drug effects*
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Receptors, Prostaglandin / metabolism
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Receptors, Thromboxane
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Receptors, Thromboxane A2, Prostaglandin H2
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Thromboxane A2 / analogs & derivatives
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Thromboxane A2 / antagonists & inhibitors
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Thromboxane A2 / metabolism*
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Thromboxane A2 / pharmacology
Substances
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Hydroxyeicosatetraenoic Acids
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Inositol Phosphates
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Platelet Aggregation Inhibitors
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Prostaglandin Endoperoxides, Synthetic
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Prostaglandins H
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Receptors, Prostaglandin
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Receptors, Thromboxane
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Receptors, Thromboxane A2, Prostaglandin H2
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Prostaglandin H2
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U 44069
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Thromboxane A2
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12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
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I-PTA-OH