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首页> 外文期刊>American Journal of Physiology >Glucocorticoids stimulate cation absorption by semicircular canal duct epithelium via epithelial sodium channel.
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Glucocorticoids stimulate cation absorption by semicircular canal duct epithelium via epithelial sodium channel.

机译：糖皮质激素通过上皮钠通道刺激半圆形管导管上皮吸收阳离子。

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The semicircular canal duct (SCCD) epithelium is a vestibular epithelial domain that was recently shown to actively contribute to endolymph homeostasis by Cl(-) secretion under control of beta(2)-adrenergic stimulation. By analogy to other Cl(-) secretory epithelia, we hypothesized that SCCD also provides an active absorptive pathway for Na(+) under corticosteroid control. Measurements of short-circuit current (I(sc)) demonstrated stimulation (7-24 h) by the glucocorticoids hydrocortisone (EC(50) 13 nM), corticosterone (33 nM), prednisolone (70 nM), and dexamethasone (13 nM) over physiologically and therapeutically relevant concentrations and its block by amiloride (IC(50) 470 nM) and benzamil (57 nM), inhibitors of the epithelial sodium channel (ENaC). I(sc) was also partially inhibited by basolateral ouabain and Ba(2+), indicating the participation of Na(+)-K(+)-ATPase and a K(+) channel in Na(+) transport. By contrast, aldosterone stimulated I(sc) only at unphysiologically high concentrations (EC(50) 102 nM). The action of all steroids was blocked by mifepristone (RU-486; K(d) approximately 0.3 nM) but not by spironolactone (K(d) approximately 0.7 microM). Expression of mRNA for the alpha-, beta-, and gamma-subunits of ENaC was demonstrated in the presence and absence of glucocorticoids. These findings are the first to identify SCCD in the vestibular labyrinth as a site of physiologically significant ENaC-mediated Na(+) absorption and osmotically coupled water flux. They further demonstrate regulation of Na(+) transport by natural and therapeutic glucocorticoids. The results provide for the first time an understanding of the therapeutic benefit of glucocorticoids in the treatment of Meniere's disease, a condition that is associated with increased luminal fluid volume.
机译：半规管（SCCD）上皮是一个前庭上皮域，最近被证明可以通过在β（2）-肾上腺素能刺激的控制下通过Cl（-）分泌来主动促进内淋巴的稳态。通过类比其他Cl（-）分泌上皮细胞，我们假设SCCD还为皮质类固醇控制下的Na（+）提供了一个活跃的吸收途径。短路电流（I（sc））的测量显示了糖皮质激素氢化可的松（EC（50）13 nM），皮质酮（33 nM），泼尼松龙（70 nM）和地塞米松（13 nM）的刺激（7-24小时） ）超过生理和治疗相关浓度，并被上皮钠通道（ENaC）抑制剂阿米洛利（IC（50）470 nM）和苯扎米尔（57 nM）阻断。 I（sc）也被基底外侧哇巴因和Ba（2+）部分抑制，表明Na（+）-K（+）-ATPase和K（+）通道参与Na（+）转运。相比之下，醛固酮仅以非生理性高浓度（EC（50）102 nM）刺激I（sc）。米非司酮（RU-486; K（d）约0.3 nM）阻止了所有类固醇的作用，但螺内酯（K（d）约0.7 microM）阻止了所有类固醇的作用。在存在和不存在糖皮质激素的情况下，证明了ENaC的α，β和γ亚基的mRNA表达。这些发现是第一个将前庭迷宫中的SCCD识别为生理上重要的ENaC介导的Na（+）吸收和渗透耦合水通量的站点。他们进一步证明了天然和治疗性糖皮质激素对Na（+）转运的调节。该结果首次提供了对糖皮质激素在美尼尔氏病治疗中的治疗益处的了解，该疾病与腔内液体体积增加有关。

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