Acetamide-45抑制电场刺激及醋氯甲胆碱引起的离体气道收缩

目的:探讨新型抗变态反应药N-对氟苄基-3-(N-4-吡啶)-乙酰胺]-吲哚-45 (acetamide-45)对电场刺激引起的大鼠离体气管/支气管收缩,及醋氯甲胆碱引起的豚鼠离体气管收缩的影响.方法:以acetamide-45预处理标本后,①记录电场刺激引起胆碱能神经兴奋所致的标本收缩,观察acetamide-45的作用;②以累积剂量法给予醋氯甲胆碱,观察acetamide-45对醋氯甲胆碱量效曲线的影响,气管张力的变化通过换能器转变为电信号并由记录仪记录.结果:Acetamide-45 (1～30 μmol·L-1)能浓度依赖性地抑制电场刺激引起的大鼠气管/支气管的胆碱能收缩,其在气管的IC50(95%可信限)为10.74(8.87～13.00)μmol·L-1,在支气管的IC50(95%可信限)为18.83(14.57～24.33)μmol·L-1.Acetamide-45浓度依赖地抑制醋氯甲胆碱引起的豚鼠离体气管收缩,3～30 μmol·L-1 acetamide-45使醋氯甲胆碱的量效曲线的最大效应下降24.6%～43.2%,EC50增大3.1～21.4倍.结论:acetamide-45抑制离体气道平滑肌收缩的作用,可能是通过非特异性抑制乙酰胆碱和胆碱能受体结合而产生的.

Inhibition of acetamide-45 on airway smooth muscle contraction induced by electric field stimulation and methacholine in vitro

OBJECTIVE: To investigate the effects of the new antiallergic agent N-(pyridin-4-yl)-(indol-3-yl) acetamide-45 (acetamide-45) on electric field stimulation (EFS)-and methacholine-induced contraction of airway smooth muscle in vitro. METHODS: Contractions were induced by EFS in isolated trachea and bronchus of rats or by cumulative methacholine concentrations in isolated trachea of guinea pigs. Changes in isometric force of isolated airway smooth muscle were measured by force transducers and recorded on a multi-channel polygraph recorder. RESULTS: Acetamide-45 inhibited the contraction induced by EFS in isolated rat airway. The IC50 was 10.74 (95% CI 8.87-13.00) micromol.L(-1) and 18.83 (95% CI 14.57-24.33) micromol.L(-1) in tracheae and bronchi, respectively. Acetamide-45 also inhibited methacholine-induced contractile response of isolated guinea pig trachea in a concentration-dependent manner. At concentrations of 3, 10, 30 micromol.L(-1) acetamide-45 significantly decreased maximal contractile response of methacholine by 24.6%-43.2% and increased EC50 of methacholine by 3.1-to 21.4-fold. CONCLUSION: Acetamide-45 inhibits EFS-or methacholine-induced contraction of isolated airway smooth muscle, and these effects might be non-specific inhibition on cholinergic receptor.