title: The endocannabinoid anandamide inhibits kinin B1 receptor sensitization through cannabinoid CB1 receptor stimulation in human umbilical vein.
abstract: The possible inhibition of kinin B(1) receptor up-regulation by arachidonoylethanolamide (anandamide) was evaluated in isolated human umbilical vein. Anandamide and its metabolically stable analogue, R-N-(2-Hydroxy-1-methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (R-(+)-methanandamide), produced a selective and dose-dependent inhibition of kinin B(1) receptor-sensitized contractile responses. The inhibitory effect of anandamide on B(1) receptor-sensitized responses failed to be modified either by 5-biphenyl-4-ylmethyl-tetrazole-1-carboxylic acid dimethylamide (LY2183240), a selective anandamide uptake inhibitor, or 6-Iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl) methanone (AM630), selective cannabinoid CB(2) receptor antagonist. However, the cannabinoid CB(1) receptor antagonist, N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), abolished anandamide effects on kinin B(1) receptor sensitization. The present results provide strong pharmacological evidence indicating that endocannabinoid anandamide inhibits kinin B(1) receptor up-regulation through cannabinoid CB(1) receptor stimulation in human umbilical vein.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, 2155 Paraguay St., 9th floor, Ciudad Autónoma de Buenos Aires (CP 1121), Argentina.
authors.forename: Facundo Germán
authors.initials: FG
authors.lastname: Pelorosso
authors.forename: Juan Ezequiel
authors.initials: JE
authors.lastname: Gago
authors.forename: Giannina
authors.initials: G
authors.lastname: Del Rey
authors.forename: Sofía Diana
authors.initials: SD
authors.lastname: Menéndez
authors.forename: Andrea Emilse
authors.initials: AE
authors.lastname: Errasti
authors.forename: Rodolfo Pedro
authors.initials: RP
authors.lastname: Rothlin
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology*; D065169:Bradykinin B1 Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D006801:Humans; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D014471:Umbilical Veins / Q000187:drug effects* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D001095:Arachidonic Acids; D065169:Bradykinin B1 Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043783:Receptor, Bradykinin B1; D043884:Receptor, Cannabinoid, CB1; C078814:anandamide