Abstract
The present study investigated the mechanism by which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit platelet activation induced by thromboxane A2. DHA was found to be more potent than EPA in blocking platelet aggregation induced by the stable thromboxane A2 mimetic, U46619. Furthermore, this inhibition by DHA or EPA was competitive. Binding studies using 3H-U46619 demonstrated that both EPA and DHA interact with the platelet thromboxane receptor. The potency of the inhibition of binding corresponded with that seen for the inhibition of aggregation. These results suggest that thromboxane receptor antagonism may be an important mechanism by which EPA and DHA modulate platelet reactivity in vivo.
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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Binding, Competitive
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Blood Platelets / drug effects*
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Blood Platelets / metabolism
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Docosahexaenoic Acids / pharmacology*
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Eicosapentaenoic Acid / pharmacology*
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Humans
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Lipoxygenase / metabolism
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Platelet Aggregation / drug effects
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Prostaglandin Endoperoxides, Synthetic / antagonists & inhibitors
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Prostaglandin Endoperoxides, Synthetic / blood
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Prostaglandin-Endoperoxide Synthases / metabolism
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Prostaglandins H
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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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Thromboxane A2
Substances
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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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Docosahexaenoic Acids
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Thromboxane A2
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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Eicosapentaenoic Acid
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Lipoxygenase
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Prostaglandin-Endoperoxide Synthases