雌酚酮衍生物EA303对家兔离体降结肠平滑肌的舒张作用研究

目的探讨雌酚酮衍生物（EA303）对家兔离体降结肠平滑肌的舒张作用及其机制。方法以家兔离体降结肠平滑肌为标本,观察EA303对家兔离体降结肠平滑肌的影响及可能的作用机制。结果EA303（10-5~10-4mol.L-1）可以剂量依赖性降低家兔离体降结肠平滑肌自发性收缩的张力和振幅 加入格列苯脲（10-5mol.L-1）孵育后,分别由BaCl2、KCl引起收缩的EA303的舒张量效曲线均发生明显变化,EA303的舒张作用被抑制 EA303（10-6、3×10-6mol.L-1）或维拉帕米（10-7mol.L-1）都使CaCl2累积收缩量效曲线呈剂量依赖性右移,最大反应降低且对ACh引起的第Ⅰ、第Ⅱ时相的收缩有明显影响。结论EA303舒张结肠平滑肌作用与ATP-敏感性钾通道开放有关 其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。

Relaxant effect of an estrone derivate EA303 on isolated descending colonic smooth muscle in rabbits

Objective To determine the relaxant mechanism and effect of an estrone derivate EA303 on isolated descending colonic smooth muscle in rabbits. Methods The sample was prepared by rabbit isolated descending colonic smooth muscle, and the possible mechanism was investigated. Results EA303 （10^-5-10^-4 mol· L-1 ） significantly attenuated the tension and amplitude of spontaneous contraction of isolated descending colonic smooth muscle. The re- laxing concentration-response curves of EA303 on preparations pre-contracted by BaCl2 or KCI were significantly changed before and after incubation with glibenclamide （ 10-5 mol· L-1 ）. Both incubations with EA303 （10-6 . 3 × 10-6 mol· L-1 ） and verapamil （10-7 mol· L-1 ） shifted the concentration-response curves of CaCl2 to the right and the rightward shift of the concentration-response curves of CaCl2 was dose-dependent with the maximum responses significantly decreased. EA303, similar to that produced by verapamil, had significant effect on contraction of Phase Ⅰ and Phase Ⅱ induced by ACh. Conclusion The relaxant mechanism of EA303 on isolated descending colonic smooth muscle may be related to K＋-ATP opening. EA303, like that produced by verapamil, could block the calcium channel and inhibit the release of intracellular calcium.