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目的研究选择性M2受体阻断剂(MET)对人支气管平滑肌功能性拮抗的影响和M2受体在功能性拮抗中的作用。方法将自手术病人所得的离体支气管段随机分若干组(n=8),用电生理的方法测得不同浓度乙酰胆碱(ACh,1、10、100μmol/L)对人离体支气管平滑肌的收缩作用和对β受体激动剂异丙肾上腺素药理效应的功能性拮抗。相同方法和条件下,用选择性M2受体阻断剂MET(0.1～1.0μmol/L)或/和选择性M3受体阻断剂4-DAMP mustard(30 nmol/L)预处理人离体支气管后,观察实验结果。结果 不同剂量ACh使得异丙肾上腺素量-效曲线右移。ACh 100μmol/L时,异丙肾上腺素效能强度下降33倍(-logEC50=-1,49±0.16),Emax下降30％。MET阻断上述胆碱能功能拮抗现象,对组织胺引起的没有作用。另外,在人离体支气管平滑肌M3受体被4-DAMP mustard(30 nmol/L)完全乙酰化的情况下,MET同样阻断ACh对异丙肾上腺素效应的功能拮抗作用。结论M2受体的激活可间接引起人支气管平滑肌的收缩,降低β受体效应,产生胆碱能功能性拮抗现象。
Objective To investigate the effect of selective M2 receptor blocker (MET) on functional bronchial smooth muscle antagonism and M2 receptor in functional antagonism. Methods The isolated bronchial segments obtained from patients undergoing surgery were randomly divided into groups (n = 8). Electrophysiological methods were used to measure the contractile effects of different concentrations of acetylcholine (ACh, 1, 10 and 100 μmol / L) on isolated human bronchial smooth muscle Function and functional antagonism of the pharmacological effects of the beta receptor agonist isoproterenol. Under the same method and conditions, human ex vivo was pretreated with selective M2 receptor blocker MET (0.1-1.0 μmol / L) or / and selective M3 receptor blocker 4-DAMP mustard (30 nmol / L) Bronchial, observe the experimental results. RESULTS Different doses of ACh shifted the isoprenaline volume-effect curve to the right. ACh 100μmol / L, the potency of isoproterenol decreased 33-fold (-logEC50 = -1,49 ± 0.16), Emax decreased by 30%. MET blocks the above antagonism of cholinergic function, causing no effect on histamine. In addition, MET also blocks the functional antagonism of ACh to the isoproterenol effect in the event that human bronchial smooth muscle M3 receptor is fully acetylated by 4-DAMP mustard (30 nmol / L). Conclusion The activation of M2 receptor can indirectly cause the bronchial smooth muscle contraction, reduce the β receptor effect, produce cholinergic functional antagonism.