雌酚酮衍生物EA303对家兔离体空肠平滑肌的舒张作用

Relaxant effect of an estrone derivate EA303 on isolated jejunum smooth muscle of rabbits

目的探讨雌酚酮衍生物EA303对家兔离体空肠平滑肌的作用及其机制。方法以家兔离体空肠平滑肌条为标本,观察EA303对空肠平滑肌自主活动的影响;通过对比0.1μmol·L^-1普萘洛尔孵育前后EA303对高钾液（KCl）和氯化乙酰胆碱的舒张量效曲线,研究EA303对β受体的作用及对氯化钙累积收缩量效曲线的影响,并与维拉帕米相比较。结果10-100μmol·L^-1EA303可以剂量依赖性地降低家兔离体空肠平滑肌自发性收缩的张力和振幅;加入0.1μmol·L^-1普萘洛尔孵育后,EA303对高钾液（KCl）和氯化乙酰胆碱收缩的空肠平滑肌的舒张量效曲线发生明显变化,EA303对KCl引起收缩的舒张作用被抑制,对氯化乙酰胆碱引起收缩的舒张作用被增强。1、3μmol·L^-1EA303或0.1μmol·L^-1维拉帕米都使CaCl2累积收缩量效曲线呈剂量依赖性右移,且最大反应降低;EA303和维拉帕米对氯化乙酰胆碱引起的第Ⅰ时相、第Ⅱ时相的收缩有明显影响。结论EA303舒张空肠平滑肌作用与β受体有关;EA303舒张作用与维拉帕米相似,可阻断电压依赖性钙通道和抑制细胞内钙释放。

Objective To study the relaxant effect mechanism of an estrone derivate EA303 on isolated jejunum smooth muscle of rabbits.Methods The sample was prepared with rabbit isolated jejunum smooth muscle,the effect of EA303 on the spontaneous contractions of jejunum smooth muscle was investigated.The effect of EA303 on β receptor was studied by observing the difference of relaxing concentration-response curves of EA303 on preparations pre-contracted with KCl or acetylcholine chloride before and after incubation with propranolol（0.1 μmol·L^-1）.The influence of EA303 on the cumulative concentration-response curves of CaCl2 was studied and verapamil was used to compare with EA303 as a noncompetitive inhibitor of Ca^2＋ channels.Results EA303（10-100 μmol·L^-1）significantly attenuated the tension and amplitude of spontaneous contraction of isolated jejunum smooth muscle.The relaxing concentration-response curves of EA303 on preparations pre-contracted by KCl or acetylcholine chloride were significantly changed after incubation with propranolol（0.1 μmol·L^-1）;The relaxing effect of EA303 on preparations induced by KCl was inhibited,but increased on preparations induced by acetylcholine chloride.Both incubation with EA303（1,3 μmol·L^-1）and verapamil（0.1 μmol·L^-1）shifted the concentration-response curves of CaCl2 to the right and the rightward shift of the concentration-response curves of CaCl2 were dose-dependent with the maximum responses of that significantly decreased.EA303,similar to that produced by verapamil had significant effect on contraction of the first phase and second phase induced by acetylcholine chloride.Conclusions The relaxant effect of EA303 on jejunum smooth muscle has relationship with β receptor EA303,like that produced by verapamil can block calcium channel and inhibit the releasing of intracellular calcium.