Pelorosso Facundo Germán, Gago Juan Ezequiel, Del Rey Giannina, Menéndez Sofía Diana, Errasti Andrea Emilse, Rothlin Rodolfo Pedro
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, 2155 Paraguay St., 9th floor, Ciudad Autónoma de Buenos Aires (CP 1121), Argentina.
Eur J Pharmacol. 2009 Jan 5;602(1):176-9. doi: 10.1016/j.ejphar.2008.10.058. Epub 2008 Nov 11.
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.
在分离的人脐静脉中评估了花生四烯酸乙醇酰胺（阿南达米德）对激肽B(1)受体上调的可能抑制作用。阿南达米德及其代谢稳定类似物R-N-(2-羟基-1-甲基乙基)-5Z,8Z,11Z,14Z-二十碳四烯酰胺（R-(+)-甲烷阿南达米德）对激肽B(1)受体致敏的收缩反应产生了选择性且剂量依赖性的抑制作用。阿南达米德对B(1)受体致敏反应的抑制作用，既未被选择性阿南达米德摄取抑制剂5-联苯-4-基甲基-四氮唑-1-羧酸二甲酰胺（LY2183240），也未被选择性大麻素CB(2)受体拮抗剂6-碘-2-甲基-1-[2-(4-吗啉基)乙基]-1H-吲哚-3-基](4-甲氧基苯基)甲酮（AM630）所改变。然而，大麻素CB(1)受体拮抗剂N-(哌啶-1-基)-5-(4-碘苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-甲酰胺（AM251）消除了阿南达米德对激肽B(1)受体致敏的作用。目前的结果提供了有力的药理学证据，表明内源性大麻素阿南达米德通过刺激人脐静脉中的大麻素CB(1)受体来抑制激肽B(1)受体的上调。
