title: Anandamide inhibits endothelin-1 production by human cultured endothelial cells: a new vascular action of this endocannabinoid.
abstract: The endogenous cannabinoid receptor agonist anandamide (AEA) exerts vascular effects such as vasodilatation and hypotension. In this study, we determined the effect of AEA on endothelin-1 production by cultured human umbilical vein endothelial cells. Anandamide (>or=5 micromol/l) significantly decreased endothelin-1 production in a dose-dependent manner, a response not affected by the specific CB1 receptor antagonist/inverse agonist SR-141716A. Adenosine, via activation of adenosine receptors (also targets for SR-141716A), was not involved in these effects. Conversely, AEA increased nitric oxide (NO) production, an effect inhibited by SR-141716A, indicating the involvement of CB1 receptors. Therefore, we hypothesize that AEA effects on endothelial cells may lead to vasodilatation through independent concerted mechanisms, involving a non-CB1 receptor-dependent inhibition of endothelin-1 production and a CB1-mediated increase of NO.
authors.affiliation: Laboratorio de Hormonas y Receptores, Instituto de Nutrición y Tecnología de los Alimentos, INTA, Universidad de Chile, Santiago, Chile. amronco@inta.cl
authors.forename: Ana María
authors.initials: AM
authors.lastname: Ronco
authors.forename: Miguel
authors.initials: M
authors.lastname: Llanos
authors.forename: Daniela
authors.initials: D
authors.lastname: Tamayo
authors.forename: Sandra
authors.initials: S
authors.lastname: Hirsch
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D014970:Xanthines / Q000494:pharmacology
chemical_list: C515416:8-(3-Chlorostyryl)-1,3,7-trimethylxanthine; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D019332:Endothelin-1; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014970:Xanthines; D009569:Nitric Oxide; C010192:9-(2-hydroxy-3-nonyl)adenine; D000225:Adenine; D000241:Adenosine; D000077285:Rimonabant; C078814:anandamide