title: The anandamide effect on NO/cGMP pathway in human platelets.
abstract: In this study the effect of the endocannabinoid anandamide on platelet nitric oxide (NO)/cGMP pathway was investigated. Data report that anandamide in a dose-and time-dependent manner increased NO and cGMP levels and stimulated endothelial nitric oxide synthase (eNOS) activity. These parameters were significantly reduced by LY294002, selective inhibitor of PI3K and by MK2206, specific inhibitor of AKT. Moreover anandamide stimulated both eNOSser1177 and AKTser473 phosphorylation. Finally the anandamide effect on NO and cGMP levels, eNOS and AKT phosphorylation/activation were inhibited by SR141716, specific cannabinoid receptor 1 antagonist, supporting the involvement of anandamide binding to this receptor. Overall data of this report indicate that low concentrations of anandamide, through PI3K/AKT pathway activation, stimulates eNOS activity and increases NO levels in human platelets. In such way anandamide contributes to extend platelet survival.
authors.affiliation: Department Experimental Medicine, Biochemistry Section, Genoa University, Genoa, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Signorello
authors.forename: Enrica
authors.initials: E
authors.lastname: Giacobbe
authors.forename: Mario
authors.initials: M
authors.lastname: Passalacqua
authors.forename: Giuliana
authors.initials: G
authors.lastname: Leoncini
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D063388:Endocannabinoids; D057075:Enzyme Assays; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D002956:Citrulline; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP; D002118:Calcium; C078814:anandamide