Dumoulin M, Salvail D, Gaudreault S B, Cadieux A, Rousseau E
Le Bilarium, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
Am J Physiol. 1998 Sep;275(3):L423-31. doi: 10.1152/ajplung.1998.275.3.L423.
Epoxyeicosatrienoic acids (EETs) relax various smooth muscles by increasing outward K+ movement, but the molecular mode of action of EET regioisomers remains to be clarified. The effects of EETs were investigated on bovine airway smooth muscle tone and on reconstituted Ca2+-activated K+ (KCa) channels. 5,6-EET and 11, 12-EET induced dose-dependent relaxations of precontracted bronchial spirals. These effects were partly abolished by 10 nM iberiotoxin. Bilayer experiments have shown that 0.1-10 microM 11,12-EET produced up to fourfold increases in the open probability of KCa channels from the cis (extracellular) side by enhancing the mean open time constant and reducing the long closed time constant, without affecting the unitary conductance. EET-induced activations were blocked by 10 nM iberiotoxin. Addition of vehicles or other lipids as well as of GTP and guanosine 5'-O-(3-thiotriphosphate) in the absence of EET had no effect on channel activity. Thus EETs directly activate KCa channels from airway smooth muscle through an interaction with the extracellular face of the channel. We propose that EETs could represent candidate molecules as epithelium-derived hyperpolarizing factors.
环氧二十碳三烯酸（EETs）通过增加外向钾离子运动来舒张各种平滑肌，但EET区域异构体的分子作用模式仍有待阐明。研究了EETs对牛气道平滑肌张力和重组钙激活钾通道（KCa）的影响。5,6-EET和11,12-EET诱导预收缩支气管螺旋条产生剂量依赖性舒张。这些作用部分被10 nM埃博毒素所消除。双层实验表明，0.1-10 μM 11,12-EET通过增加平均开放时间常数和缩短长时间关闭时间常数，使KCa通道从顺式（细胞外侧）开放概率增加至四倍，而不影响单位电导。EET诱导的激活被10 nM埃博毒素阻断。在无EET的情况下添加溶剂或其他脂质以及GTP和鸟苷5'-O-（3-硫代三磷酸）对通道活性无影响。因此，EETs通过与通道细胞外表面相互作用直接激活气道平滑肌的KCa通道。我们认为EETs可能是上皮衍生超极化因子的候选分子。
