Novakovic Radmila, Milovanovic Slobodan, Protic Dragana, Djokic Jelena, Heinle Helmut, Gojkovic-Bukarica Ljiljana
Department of Clinical Pharmacology, Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):181-6. doi: 10.1111/j.1742-7843.2007.00096.x.
The effects of the K(+) channel opener, pinacidil on the spontaneous rhythmic contractions and contractions provoked by electrical field stimulation (50 Hz) or by oxytocin were investigated in the isolated uterus of the non-pregnant rat in oestrus. Pinacidil produced more potent inhibition of oxytocin-elicited contractions than of spontaneous rhythmic contractions or electrical field stimulation-induced contractions. Glibenclamide, a selective blocker of adenosine triphosphate (ATP)-sensitive K(+) (K(ATP)) channels, antagonized the pinacidil-induced inhibition of contractions elicited by oxytocin in a competitive manner. However, the pinacidil-induced inhibition of electrical field stimulation-elicited contractions and spontaneous rhythmic contractions was antagonized non-competitively by glibenclamide. In the uterine strips pre-contracted with 80 mM K(+), the pinacidil-induced maximal relaxation was not affected. The present data show that pinacidil exhibits potent relaxant properties in the rat non-pregnant uterus in oestrus and therefore should be taken into account as a possible agent for treatment of dysmenorrhoea. Based on glibenclamide affinity, it appears that the inhibitory response to pinacidil involves K(ATP )channels. We need further investigations to explain why the interaction between glibenclamide and pinacidil in this experimental model depends on the nature of contractions. The ability of pinacidil to completely relax the rat non-pregnant uterus pre-contracted with K(+)-rich solution suggests that K(+) channel-independent mechanism(s) also play a part in its relaxant effect.
在处于发情期的未孕大鼠离体子宫中,研究了钾离子通道开放剂吡那地尔对自发节律性收缩以及由电场刺激(50Hz)或催产素引发的收缩的影响。吡那地尔对催产素诱发的收缩的抑制作用比对自发节律性收缩或电场刺激诱发的收缩的抑制作用更强。格列本脲是三磷酸腺苷(ATP)敏感性钾离子(KATP)通道的选择性阻断剂,它以竞争性方式拮抗吡那地尔对催产素诱发的收缩的抑制作用。然而,格列本脲以非竞争性方式拮抗吡那地尔对电场刺激诱发的收缩和自发节律性收缩的抑制作用。在用80mM钾离子预收缩的子宫条中,吡那地尔诱导的最大舒张不受影响。目前的数据表明,吡那地尔在处于发情期的未孕大鼠子宫中具有强大的舒张特性,因此应将其视为治疗痛经的一种可能药物。基于格列本脲的亲和力,似乎对吡那地尔的抑制反应涉及KATP通道。我们需要进一步研究来解释为什么在这个实验模型中格列本脲与吡那地尔之间的相互作用取决于收缩的性质。吡那地尔能够使用富含钾离子的溶液预收缩的未孕大鼠子宫完全舒张,这表明不依赖钾离子通道的机制在其舒张作用中也起作用。