Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Mol Cell Neurosci. 2011 Oct;48(2):137-41. doi: 10.1016/j.mcn.2011.07.002. Epub 2011 Jul 19.
The administration of progesterone as a neuroprotective agent following traumatic brain injury has recently entered phase III clinical trials. Previous work has demonstrated that therapeutic concentrations of progesterone decrease excitotoxicity through direct inhibition of voltage-gated calcium channels, an action independent of the nuclear progesterone receptor. Here we report using cultured rat striatal neurons that these same concentrations of progesterone also block voltage-gated potassium channels, sodium channels and GABA(A) currents. The actions of progesterone act at the surface membrane of neurons in a steroid specific, voltage-independent, concentration-dependent manner. Notably, these broad actions of progesterone on ion channel and neurotransmitter receptor function mirror those of dihydropyridines, and indicate potential shared mechanisms of action, the prospective of additional therapeutic applications, and possibly, untoward effects.
孕激素作为颅脑损伤后的神经保护剂的应用最近已进入 III 期临床试验。先前的工作表明，治疗浓度的孕激素通过直接抑制电压门控钙通道来减少兴奋性毒性，这种作用与核孕激素受体无关。在这里，我们报告使用培养的大鼠纹状体神经元，这些相同浓度的孕激素也可阻断电压门控钾通道、钠通道和 GABA(A)电流。孕激素在神经元的表面膜上以类固醇特异性、电压非依赖性、浓度依赖性的方式起作用。值得注意的是，孕激素对离子通道和神经递质受体功能的广泛作用与二氢吡啶类药物相似，这表明可能存在共同的作用机制，具有更多的治疗应用前景，也可能存在不良作用。
