Mineralocorticoid receptor stimulation induces urinary storage dysfunction via upregulation of epithelial sodium channel expression in the rat urinary bladder epithelium
Mineralocorticoid receptor stimulation induces urinary storage dysfunction via upregulation of epithelial sodium channel expression in the rat urinary bladder epithelium
复制标题
盐皮质激素受体刺激通过上调大鼠膀胱上皮上皮钠通道表达诱导尿液储存功能障碍
DOI：
10.1016/j.jphs.2016.02.004
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发表时间：
2016
期刊：
影响因子：
3.5
通讯作者：
Kimura Kazunori
中科院分区：
文献类型：
--
作者：
Yamamoto Seiji;Hotta Yuji;Maeda Kotomi;Kataoka Tomoya;Maeda Yasuhiro;Hamakawa Takashi;Sasaki Shoichi;Yasui Takahiro;Asai Kiyofumi;Kimura Kazunori
我们的目的是评估盐皮质激素受体（MR）在大鼠膀胱的表达和MR上皮钠通道（ENaC）途径在控制膀胱功能的10-12周龄，雄性SD大鼠的生理作用。首先，我们检测了MR的mRNA表达以及MR和ENaC-α蛋白在膀胱中的定位。在未处理的大鼠膀胱中观察到MR mRNA表达，MR和ENaC-α蛋白定位于上皮。接下来，用载体（对照）或氟氢可的松（MR激动剂）处理大鼠3天，并在第4天评价ENaC-α蛋白表达水平和膀胱功能。ENaC-α蛋白表达在氟氢可的松治疗组显著高于对照组。此外，膀胱内灌注生理盐水和阿米洛利（ENaC抑制剂）期间进行膀胱测压。虽然输注生理盐水期间氟氢可的松组的收缩间期（ICI）显著短于对照组，但输注阿米洛利使氟氢可的松组的ICI正常化。然而，未观察到组内或组间最大膀胱内压差异。综上所述，MR蛋白定位于大鼠膀胱上皮，并可能调节ENaC表达和膀胱传入输入。MR-ENaC通路可能是改善储存症状的治疗靶点。
We aimed to evaluate mineralocorticoid receptor (MR) expression in rat bladder and the physiological role of the MR-epithelial sodium channel (ENaC) pathway in controlling bladder function in 10–12-week-old, male Sprague–Dawley rats. First, we examined the mRNA expression of MR and localization of MR and ENaC-α proteins in the urinary bladder. MR mRNA expression was observed in untreated-rat urinary bladders, and MR and ENaC-α proteins were localized in the epithelium. Next, rats were treated with vehicle (controls) or fludrocortisone (an MR agonist) for 3 days, and ENaC-α protein expression levels and bladder function were evaluated on day 4. ENaC-α protein expression was significantly higher in fludrocortisone-treated rats than in controls. In addition, cystometry was performed during intravesical infusion of saline and amiloride (an ENaC inhibitor). While intercontraction intervals (ICIs) during saline infusion were significantly shorter in the fludrocortisone group than in the controls, infusion of amiloride normalized the ICIs in the fludrocortisone group. However, no intra- or inter-group differences in maximum intravesical pressure were observed. Taken together, MR protein is localized in the rat urinary bladder epithelium, and may regulate ENaC expression and bladder afferent input. The MR-ENaC pathway may be a therapeutic target for ameliorating storage symptoms.