Vijayakumar C, Kathirvel K, Sardar K K, Parija S C
Department of Pharmacology and Toxicology, Faculty of Veterinary Sciences and Animal Husbandry, Orissa University of Agriculture and Technology, Bhubaneswar 751 003, India.
Indian J Exp Biol. 2007 Feb;45(2):185-93.
Isolated goat detrusor muscle exhibited spontaneous contractility with an irregular amplitude and frequency. The spontaneity of detrusor muscle exhibited a mean amplitude as 11.99 +/- 0.83 mm and frequency as 1.37 +/- 0.16/min. KATP-channel openers namely, cromakalim or pinacidil (10(-7) - 10(-4) M) added cumulatively, elicited a concentration-related inhibition of both amplitude and rate of spontaneous contractions. The mean IC50 values for both amplitude and frequency for cromakalim were 3.3 x 10(-6) M and 2.9 x 10(-6) M, respectively; and for pinacidil were 2.0 x 10(-5) M and 1.5 x 10(-5) M, respectively. Glibenclamide, a KATP-channel blocker inhibited the cromakalim-induced concentration-related relaxation of spontaneous contractions with a significant increase in its mean IC50. ACh-induced concentration-related contractile response was inhibited in the presence of either cromakalim (10(-4) M) or pinacidil (10(-4) M). The mean EC50 value of ACh, in the presence of cromakalim (2.5 x 10(-3) M) was significantly increased as compared to the control (1.2 x 10(-6) M). In the presence of glibenclamide (10(-5) M) the inhibitory effect of cromakalim was significantly reduced with consequent decrease in the EC50 value (1.9 x 10(-5) M). Application of EFS (30 V and 5 ms) on goat urinary bladder strips at 1, 2, 5, 10, 20 and 30 Hz elicited frequency-related contractile responses. Both cromakalim and pinacidil caused a rightward shift in the frequency-related contractile response curve with significant increase in the mean EF25 and EF50 values, respectively. In the presence of glibenclamide (10(-4) M), the frequency-related inhibitory response curve was shifted to left with significant (P < 0.001) increase in the mean EF25, EF50 and EF75. The present results suggest that in the goat detrusor muscle, agonist and EFS-induced contractile responses were more potently inhibited by cromakalim than pinacidil with activation of glibenclamide sensitive KATP channels.
分离出的山羊逼尿肌呈现出自发性收缩，其幅度和频率不规则。逼尿肌的自发性收缩平均幅度为11.99±0.83毫米，频率为1.37±0.16次/分钟。依次添加KATP通道开放剂，即克罗卡林或吡那地尔（10^(-7) - 10^(-4) M），会引起与浓度相关的对自发性收缩幅度和速率的抑制作用。克罗卡林对幅度和频率的平均IC50值分别为3.3×10^(-6) M和2.9×10^(-6) M；吡那地尔的分别为2.0×10^(-5) M和1.5×10^(-5) M。格列本脲，一种KATP通道阻滞剂，抑制了克罗卡林诱导的与浓度相关的自发性收缩舒张，其平均IC50值显著增加。在存在克罗卡林（10^(-4) M）或吡那地尔（10^(-4) M）的情况下，乙酰胆碱诱导的与浓度相关的收缩反应受到抑制。与对照组（1.2×10^(-6) M）相比，在存在克罗卡林（2.5×10^(-3) M）时，乙酰胆碱的平均EC50值显著增加。在存在格列本脲（10^(-5) M）时，克罗卡林的抑制作用显著降低，随之EC50值下降（1.9×10^(-5) M）。对山羊膀胱条施加1、2、5、10、20和30赫兹的电场刺激（30伏和5毫秒）会引起与频率相关的收缩反应。克罗卡林和吡那地尔都使与频率相关的收缩反应曲线向右移动，平均EF25和EF50值分别显著增加。在存在格列本脲（10^(-4) M）时，与频率相关的抑制反应曲线向左移动，平均EF25、EF50和EF75显著增加（P < 0.001）。目前的结果表明，在山羊逼尿肌中，与吡那地尔相比，克罗卡林通过激活格列本脲敏感的KATP通道，更有效地抑制了激动剂和电场刺激诱导的收缩反应。
