Glucocorticoid receptors mediate mineralocorticoid-like effects in cultured collecting duct cells.
Glucocorticoid receptors mediate mineralocorticoid-like effects in cultured collecting duct cells.
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糖皮质激素受体在培养的集合管细胞中介导盐皮质激素样作用。
DOI：
10.1152/ajprenal.1990.259.4.f672
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Fejes-Toth,G
中科院分区：
文献类型：
--
作者：
Naray-Fejes-Toth,A;Fejes-Toth,G
为了研究皮质类固醇对肾离子转运的直接上皮效应，我们研究了纯糖皮质激素激动剂RU 28362和醛固酮对免疫分离的兔皮质集合管（CCD）细胞原代培养物中Na+和K+转运的影响。当在无类固醇培养基中的可渗透支持物上生长时，CCD单层表现出5.2 +/- 1.07 mV的管腔负跨上皮电位差（PD）和8.54 +/- 2.2 microA/cm 2的短路电流（SCC）。跨上皮电阻平均为660 +/- 49 Ω/cm 2。培养物主动重吸收Na+并分泌K+。醛固酮和RU 28362均显著增加PD和SCC;其作用呈时间和剂量依赖性。糖皮质激素受体拮抗剂RU 486可完全阻断RU 28362的作用，而盐皮质激素受体拮抗剂ZK 91587不能阻断RU 28362的作用。醛固酮和RU 28362均增加了Na+的浴腔浓度比，同时降低了K+的浓度比，表明Na+重吸收和K+分泌增加。Na（+）-K（+）-ATP酶单位的数量被RU 28362和醛固酮显著增强（约2倍）。这些结果表明，在培养的CCD细胞中，不仅醛固酮，而且纯糖皮质激素能够发挥盐皮质激素样作用，而后者的作用是由糖皮质激素受体介导的。由于所有研究参数对醛固酮和RU 28362的反应相似，我们推测在CCD细胞中糖皮质激素和盐皮质激素可能通过调节相同的基因起作用。
To investigate the direct epithelial effects of corticosteroids on renal ion transport, we studied the influence of the pure glucocorticoid agonist RU 28362 and aldosterone on Na+ and K+ transport in primary cultures of immunodissected rabbit cortical collecting duct (CCD) cells. When grown on permeable supports in a steroid-free medium, CCD monolayers exhibited a lumen-negative transepithelial potential difference (PD) of 5.2 +/- 1.07 mV and a short-circuit current (SCC) of 8.54 +/- 2.2 microA/cm2. Transepithelial resistance averaged 660 +/- 49 omega/cm2. The cultures actively reabsorbed Na+ and secreted K+. Both aldosterone and RU 28362 significantly increased PD and SCC; the effects were time and dose dependent. The effect of RU 28362 was completely prevented by the glucocorticoid receptor antagonist RU 486, whereas ZK 91587, a specific mineralocorticoid receptor antagonist, did not block its effect. Both aldosterone and RU 28362 increased the bath-to-lumen concentration ratio of Na+ while lowering that of K+, indicating an increased Na+ reabsorption and K+ secretion. The number of Na(+)-K(+)-ATPase units was significantly enhanced (approximately 2-fold) by both RU 28362 and aldosterone. These results demonstrate that, in cultured CCD cells, not only aldosterone but also a pure glucocorticoid is able to exert mineralocorticoid-like effects, and this latter effect is mediated by glucocorticoid receptors. Because all parameters studied responded similarly to aldosterone and RU 28362, we speculate that in CCD cells glucocorticoids and mineralocorticoids might act by regulating the same gene(s).