The endocannabinoid anandamide inhibits kinin B1 receptor sensitization through cannabinoid CB1 receptor stimulation in human umbilical vein.
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.
Pelorosso
Facundo Germán
FG
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, 2155 Paraguay St., 9th floor, Ciudad Autónoma de Buenos Aires (CP 1121), Argentina.
Gago
Juan Ezequiel
JE
Del Rey
Giannina
G
Menéndez
Sofía Diana
SD
Errasti
Andrea Emilse
AE
Rothlin
Rodolfo Pedro
RP
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
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