Janssen L J, Netherton S J, Walters D K
Asthma Research Group, Smooth Muscle Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
J Appl Physiol (1985). 2000 Feb;88(2):745-52. doi: 10.1152/jappl.2000.88.2.745.
We examined the ionic mechanisms underlying the responses of canine trachealis to superoxide (generated in vitro by using xanthine oxidase or added exogenously) and peroxide (generated spontaneously in vitro by the dismutation of superoxide or added exogenously). Although neither had any effect on resting tone, both triggered relaxations in carbachol-precontracted tissues. These relaxations were eliminated by catalase but were much less sensitive to the hydroxyl radical scavenger dimethylthiourea, indicating they were mediated primarily by peroxide. These relaxations were decreased in magnitude and/or slowed by nifedipine (10(-6) M), ouabain (10(-6) M), or tetraethylammonium (25 mM), but not by 4-aminopyridine (5 mM), and were small or absent in tissues precontracted with 30 mM KCl. Finally, peroxide triggered membrane hyperpolarization and elevated cytosolic concentration of Ca(2+) (primarily via release from the internal store). Thus peroxide-mediated relaxations seem to involve Ca(2+) release, opening of Ca(2+)-dependent K(+) channels, hyperpolarization, closure of Ca(2+) channels, and relaxation. In addition, some other free radical (hydroxyl radical?) may activate the Na(+)-K(+) pump, also hyperpolarizing the membrane and causing relaxation.
我们研究了犬气管平滑肌对超氧化物（通过黄嘌呤氧化酶体外生成或外源添加）和过氧化物（通过超氧化物歧化体外自发生成或外源添加）反应的离子机制。尽管二者对静息张力均无影响，但均可引发卡巴胆碱预收缩组织的舒张。这些舒张反应可被过氧化氢酶消除，但对羟自由基清除剂二甲基硫脲的敏感性较低，表明其主要由过氧化物介导。硝苯地平（10(-6) M）、哇巴因（10(-6) M）或四乙铵（25 mM）可使这些舒张反应的幅度降低和/或速度减慢，但4-氨基吡啶（5 mM）无此作用，且在30 mM KCl预收缩的组织中，舒张反应较小或不存在。最后，过氧化物引发膜超极化并升高胞质Ca(2+)浓度（主要通过从内质网释放）。因此，过氧化物介导的舒张似乎涉及Ca(2+)释放、Ca(2+)依赖性K(+)通道开放、超极化、Ca(2+)通道关闭以及舒张。此外，某些其他自由基（羟自由基？）可能激活Na(+)-K(+)泵，同样使膜超极化并导致舒张。
