Glucocorticoid metabolism in proximal tubules modulates angiotensin II-induced electrolyte transport.
Glucocorticoid metabolism in proximal tubules modulates angiotensin II-induced electrolyte transport.
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近曲小管中的糖皮质激素代谢调节血管紧张素 II 诱导的电解质转运。
DOI：
10.1046/j.1525-1373.1999.d01-63.x
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Ingelfinger,JR
中科院分区：
文献类型：
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作者：
Brem,AS;Bina,RB;Fitzpatrick,C;King,T;Tang,SS;Ingelfinger,JR
调节近曲小管电解质转运的激素相互作用非常复杂且尚未完全了解。由于内源性糖皮质激素和血管紧张素 II 均可影响该肾段的电解质转运，因此我们假设 11β-羟基类固醇脱氢酶 (11β-HSD) 引起的糖皮质激素局部代谢可能会改变对血管紧张素 II 的反应。研究在源自断奶 Wistar 大鼠肾脏的培养来源缺陷 SV-40 转化永生化肾近端小管细胞 (IRPTC) 中进行。这些细胞中含有的 11β-HSD 使用 NADP+，对皮质酮的表观 Km 为 1.6 μM，但仅起脱氢酶的作用（皮质酮 → 11-脱氢皮质酮）。当安装在改进的尤斯室中时，IRPTC 会产生跨膜电流，而血管紧张素 II（10 pM 至 10 μM）会增加这种钠依赖性电流。与皮质酮 (100 nM) 和 11β-HSD 抑制剂甘酸索隆 (CBX) (1 μM) 一起孵育 24 小时，然后用血管紧张素 (10 nM) 剧烈刺激的细胞，与单独暴露于皮质酮并用血管紧张素刺激的细胞相比，显示出更大的电流上升（皮质酮 + CBX：64.2% ± 20.5% 与皮质酮相比： 18.8% ± 5.9%；180 分钟时 P> 0.02）[平均值 ± SE 高于基线的百分比，n= 8/组]。细胞单独暴露于皮质酮 (100 nM) 或 CBX (1 μM) 24 小时，然后用血管紧张素 II (10 nM) 刺激，其反应与对照相似。因此，当局部 11β-HSD 受到抑制时，糖皮质激素可以增强近曲小管上皮细胞中血管紧张素 II 诱导的电解质转运。
The hormonal interactions that regulate electrolyte transport in the proximal tubule are complex and incompletely understood. Since endogenous glucocorticoids and angiotensin II each can affect electrolyte transport in this renal segment, we hypothesized that local metabolism of glucocorticoids by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) might alter the response to angiotensin II. Studies were conducted in cultured origin defective SV-40 transformed immortalized renal proximal tubule cells (IRPTC) derived from weanling Wistar rat kidney. The 11β-HSD contained in these cells uses NADP+, has an apparentKmfor corticosterone of 1.6 μM, but functions only as a dehydrogenase (corticosterone → 11-dehydro-corticosterone). When mounted in modified Ussing chambers, IRPTC generate a transmembrane current, and angiotensin II (10 pMto 10 μM) increases this sodium-dependent current. Cells incubated with corticosterone (100 nM) and the 11β-HSD inhibitor carbenoxolone (CBX) (1 μM) for 24 hr and then acutely stimulated with angiotensin (10 nM) show a greater rise in current than do cells exposed to corticosterone alone and stimulated with angiotensin (corticosterone + CBX: 64.2% ± 20.5% vs. corticosterone: 18.8% ± 5.9%;P> 0.02 at 180 min)[mean ± SE percentage above baseline,n= 8/group]. Cells exposed to corticosterone (100 nM) or CBX (1 μM) alone for 24 hr and then stimulated with angiotensin II (10 nM) had responses similar to controls. Thus glucocorticoids can enhance angiotensin II-induced electrolyte transport in proximal tubule epithelial cells when local 11β-HSD is inhibited.