Abstract
Anandamide (ANA), a cannabinoid receptor ligand, stimulated platelet aggregation at concentrations similar to those of arachidonic acid (AA). The aggregating effect of ANA was inhibited by aspirin but not by SR-141716, a cannabinoid receptor antagonist. In addition, HU-210, a cannabinoid receptor agonist, failed to induce platelet activation. Radiolabelling experiments showed that exogenous ANA was cleaved by platelets into AA through a phenylmethylsulfonyl fluoride (PMSF)-sensitive pathway. In agreement, PMSF was shown to abolish the aggregating effect of ANA. In conclusion, ANA is able to induce platelet activation via its cleavage by a PMSF-sensitive amidase activity, leading to the release of AA which in turn activates platelets.
MeSH terms
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / pharmacology
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Arachidonic Acid / metabolism*
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Arachidonic Acids / metabolism
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Arachidonic Acids / pharmacology*
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Aspirin / pharmacology
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Drug Interactions
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Endocannabinoids
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Enzyme Inhibitors / pharmacology
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Lipoxygenase / metabolism
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Phenylmethylsulfonyl Fluoride / pharmacology
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Platelet Aggregation / drug effects*
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Polyunsaturated Alkamides
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Prostaglandin-Endoperoxide Synthases / metabolism
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Rabbits
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Tritium
Substances
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Adjuvants, Immunologic
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Anti-Inflammatory Agents, Non-Steroidal
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Arachidonic Acids
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Endocannabinoids
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Enzyme Inhibitors
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Polyunsaturated Alkamides
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Tritium
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Arachidonic Acid
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Phenylmethylsulfonyl Fluoride
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Lipoxygenase
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Prostaglandin-Endoperoxide Synthases
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Aspirin
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anandamide