Steroid hormone stimulation of Na+ transport in A6 cells is mediated via glucocorticoid receptors.
Steroid hormone stimulation of Na+ transport in A6 cells is mediated via glucocorticoid receptors.
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A6 细胞中 Na 转运的类固醇激素刺激是通过糖皮质激素受体介导的。
DOI：
10.1152/ajpcell.1993.264.4.c875
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Stokes,JB
中科院分区：
文献类型：
--
作者：
Schmidt,TJ;Husted,RF;Stokes,JB
来源于蟾蜍肾的A6细胞系在培养中形成极化的高分化上皮单层，已被用作研究醛固酮调节跨上皮钠离子转运的实验模型。在本研究中，我们评估了糖皮质激素和盐皮质激素受体在介导这种增强的电源性Na+转运中的特殊作用(S)，这种作用是通过实验测量的短路电流的增加来实现的。我们的数据表明，特定的糖皮质激素激动剂(100nM)，包括RU 28362和RU 26988，可引起“盐皮质激素样”增加，该作用可被糖皮质激素拮抗剂RU 38486阻断，但不受盐皮质激素拮抗剂RU 28318和RU 26752的影响。醛固酮(100nM)的兴奋作用也可被RU 38486阻断，但不能被盐皮质激素拮抗剂阻断。这些数据扩展了早期的研究，即在该细胞系中，尽管存在明显正常的盐皮质激素受体，但醛固酮通过与糖皮质激素受体相对较低的亲和力(解离常数Kd相当于25-50 nM)来介导其生理效应。我们的体外生化研究还表明，A6糖皮质激素受体复合体可以被热激活或转化为DNA结合形式，从而改变了阴离子交换树脂的洗脱曲线。因此，根据几个标准，这些两栖糖皮质激素受体看起来与经典的哺乳动物受体非常相似，并能够介导醛固酮对Na+净转运的所有刺激作用。
The A6 cell line derived from the toad kidney forms polarized, highly differentiated epithelial monolayers in culture and has been utilized as an experimental model for studying regulation of transepithelial Na+ transport by aldosterone. In the present study we evaluated the specific role(s) of glucocorticoid and mineralocorticoid receptors in mediating this enhanced electrogenic Na+ transport, which was measured experimentally as an increase in short-circuit current (Isc). Our data demonstrate that specific glucocorticoid agonists (100 nM), including RU 28362 and RU 26988, elicit “mineralocorticoid-like” increases in Isc that are blocked by the glucocorticoid antagonist RU 38486 but are unaffected by mineralocorticoid antagonists including RU 28318 and RU 26752. The stimulatory effects of aldosterone (100 nM) were also blocked by RU 38486 and not by mineralocorticoid antagonists. These data extend earlier studies suggesting that in this cell line aldosterone mediates its physiological effects via binding with relatively low affinity (dissociation constant Kd congruent to 25-50 nM) to glucocorticoid receptors, despite the presence of apparently normal mineralocorticoid receptors. Our in vitro biochemical studies also demonstrate that A6 glucocorticoid receptor complexes can be thermally activated or transformed to DNA binding forms which exhibitaltered elution profiles from anion-exchange resins. Thus, based on several criteria, these amphibian glucocorticoid receptors appear very similar to classical mammalian receptors and are capable of mediating all of the stimulatory effects of aldosterone on net Na+ transport.