Activation of rabbit blood platelets by anandamide through its cleavage into arachidonic acid.
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.
Braud
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Unité des Venins, Institut Pasteur, 25 rue du Docteur Roux, 75724, Paris, France.
Bon
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C
Touqui
L
L
Mounier
C
C
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D004347:Drug Interactions; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D053284:Polyunsaturated Alkamides; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D014316:Tritium
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D053284:Polyunsaturated Alkamides; D014316:Tritium; D016718:Arachidonic Acid; D010664:Phenylmethylsulfonyl Fluoride; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; C078814:anandamide