Anandamide inhibits endothelin-1 production by human cultured endothelial cells: a new vascular action of this endocannabinoid.
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.
Ronco
Ana María
AM
Laboratorio de Hormonas y Receptores, Instituto de Nutrición y Tecnología de los Alimentos, INTA, Universidad de Chile, Santiago, Chile. amronco@inta.cl
Llanos
Miguel
M
Tamayo
Daniela
D
Hirsch
Sandra
S
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
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