钩藤碱对大鼠膀胱逼尿肌舒缩作用的影响

目的观察钩藤碱(rhynchophylline,Rhy)对离体大鼠逼尿肌的作用并探讨其作用机制。方法采用逼尿肌体外张力实验法检测Rhy对大鼠逼尿肌L-型钙通道(ICa-L)及大电导钙离子激活钾离子通道(BKCa)作用。以维拉帕米为对照观察膀胱逼尿肌肌条的收缩及对乙酰胆碱(ACh)依赖细胞内、外钙所致肌条收缩程度的拮抗作用。结果 Rhy和BKCa激动剂NS1619作用相似,亲和力指数(pD2)分别为4.78±0.17、4.53±0.22;BKCa拮抗剂iberiotoxin能竞争性拮抗Rhy,使Rhy累积量效曲线平行右移,拮抗参数(pA2)为7.27±0.16;当Rhy浓度为1~20μmo.lL-1时,使CaCl2累积量效曲线非平行右移,最大反应降低,呈非竞争性拮抗。结论 Rhy通过离子通道(阻滞ICa-L、激活BKCa)抑制膀胱逼尿肌收缩。低浓度(10μmol.L-1)Rhy仅对细胞内钙引起的肌条收缩有抑制作用,而对细胞外钙所致的肌条收缩无影响;随着浓度的增高,Rhy对细胞内、外钙引起的肌条收缩均有抑制作用,且抑制作用逐渐增加。

Effects of rhynchophylline on the contractions of isolated rat urinary bladder strips

Objective To observe the effect of rhynchophylline(Rhy) on the role of isolated rat urinary bladder strips. Methods The effects of Rhy in large conductance calcium-activated potassium channel (BK_Ca) and L-type calcium channel by applying the method of tension in vitro were detected. Moreover, the effect on the intracelluar or extracellular Ca²⁺-dependent contraction induced by acetylcholine (Ach) in isolated rat urinary bladder strips were observed by using verapamil as the positive control. Results Similar with BK_Ca agonist NS1619, Rhy significantly inhibited the CaCl₂-induced contraction of isolated rat urinary bladder strips with the affinity index (pD₂) of 4.78±0.17. This effect of Rhy could be antagonized competitively by iberiotoxin, the BK_Ca antagonist and the cumulative dose-response curves of Rhy were shifted to the right in a parallel fasion with the antagonism parameter (pA₂) of 7.27±0.16. Moreover, Rhy could shift the cumulative dose-response curves of CaCl2 to the right with lowerring the maximum response. Conclusion Rhy could inhibit the contraction of isolated rat urinary bladder strips by modulating the funtions of ion channels possibly by blocking L-type calcium channel and activating calcium-activated potassium channel. Higher concentration of Rhy inhibited the contractions of isolated rat urinary bladder strips induced by both intracellular and extracellular calcium, while lower concentration of Rhy only showed the inhibitory activity on the inctacellular calciun-induced the contractions.