Brem A S, Bina R B, Fitzpatrick C, King T, Tang S S, Ingelfinger J R
Division of Pediatric Nephrology, Rhode Island Hospital, Providence, Rhode Island 02903, USA.
Proc Soc Exp Biol Med. 1999 Jun;221(2):111-7. doi: 10.1046/j.1525-1373.1999.d01-63.x.
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 11beta-hydroxysteroid dehydrogenase (11beta-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 11beta-HSD contained in these cells uses NADP+, has an apparent Km for corticosterone of 1.6 microM, 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 pM to 10 microM) increases this sodium-dependent current. Cells incubated with corticosterone (100 nM) and the 11beta-HSD inhibitor carbenoxolone (CBX) (1 microM) 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 microM) 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 11beta-HSD is inhibited.
调节近端小管中电解质转运的激素相互作用复杂且尚未完全明确。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，我们推测11β-羟基类固醇脱氢酶（11β-HSD）对糖皮质激素的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大鼠肾脏的培养的起源缺陷型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利用NADP +，对皮质酮的表观Km为1.6μM，但仅作为脱氢酶发挥作用（皮质酮→11-脱氢皮质酮）。当安装在改良的Ussing室中时，IRPTC会产生跨膜电流，血管紧张素II（10 pM至10μM）会增加这种钠依赖性电流。用皮质酮（100 nM）和11β-HSD抑制剂甘草次酸（CBX）（1μM）孵育24小时，然后用血管紧张素（10 nM）急性刺激的细胞，其电流升高幅度大于单独暴露于皮质酮并用血管紧张素刺激的细胞（皮质酮+ CBX：64.2％+/- 20.5％对皮质酮：18.8％+/- 5.9％；在180分钟时P <0.02）[平均+/- SE高于基线的百分比，n = 8 /组]。单独用皮质酮（100 nM）或CBX（1μM）处理24小时，然后用血管紧张素II（10 nM）刺激的细胞具有与对照相似的反应。因此，当局部11β-HSD受到抑制时，糖皮质激素可增强血管紧张素II诱导的近端小管上皮细胞中的电解质转运。
