Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan.
Int Arch Allergy Immunol. 2010;152(3):295-300. doi: 10.1159/000283042. Epub 2010 Feb 12.
Although neurogenic inflammation of the airways via activation of C-fibers is thought to be important in the pathogenesis of asthma, the mechanisms regulating C-fiber activity remain uncertain.
The influence of a cannabinoid receptor agonist, WIN 55,212-2, on C-fiber activation in guinea pig airways was investigated, as was the mechanism by which cannabinoids regulate antigen-induced airway inflammation.
The inhibitory effect of WIN 55,212-2 on antigen-induced plasma extravasation was assessed in guinea pig tracheal tissues by photometric measurement of extravasated Evans blue dye after extraction with formamide.
Pretreatment with WIN 55,212-2 (0.001, 0.01 or 0.1 mg/kg) significantly and dose-dependently reduced tracheal plasma extravasation induced by inhaling a 5% ovalbumin solution for 2 min after pretreatment with a neutral endopeptidedase inhibitor (phosphoramidon at 2.5 mg/kg i.v.). A cannabinoid CB2 receptor antagonist (SR144528) blunted the inhibitory effect of WIN 55,212-2, while a cannabinoid CB1 antagonist (SR141716A) did not. Pretreatment with a neurokinin-1 receptor antagonist (FK888) significantly reduced ovalbumin-induced extravasation of Evans blue dye. Pretreatment with the combination of WIN 55,212-2 and FK888 reduced antigen-induced plasma extravasation more markedly than FK888 alone.
These findings suggest that WIN 55,212-2 inhibits C-fiber activation via the cannabinoid CB2 receptor and thus suppresses antigen-induced inflammation in guinea pig airways.
虽然通过 C 纤维激活引起的气道神经源性炎症被认为在哮喘发病机制中很重要，但调节 C 纤维活性的机制仍不清楚。
研究大麻素受体激动剂 WIN 55,212-2 对豚鼠气道 C 纤维激活的影响，并探讨大麻素调节抗原诱导的气道炎症的机制。
通过在福马酰胺中提取后用光密度法测量渗出的 Evans 蓝染料，评估 WIN 55,212-2（0.001、0.01 或 0.1 mg/kg）预处理对豚鼠气管组织中抗原诱导的血浆渗出的抑制作用。
预先给予中性内肽酶抑制剂（静脉内给予 2.5 mg/kg 的磷酰胺）后，吸入 5%卵白蛋白溶液 2 分钟，可显著剂量依赖性地减少气管血浆渗出，而预先给予大麻素 CB2 受体拮抗剂（SR144528）可减弱 WIN 55,212-2 的抑制作用，而大麻素 CB1 拮抗剂（SR141716A）则没有。预先给予神经激肽-1 受体拮抗剂（FK888）可显著减少卵白蛋白诱导的 Evans 蓝染料渗出。与 FK888 单独给药相比，WIN 55,212-2 和 FK888 的联合预处理可更显著地减少抗原诱导的血浆渗出。
这些发现表明，WIN 55,212-2 通过大麻素 CB2 受体抑制 C 纤维激活，从而抑制豚鼠气道中的抗原诱导炎症。
