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首页> 外文期刊>The Journal of Pharmacology and Experimental Therapeutics: Official Publication of the American Society for Pharmacology and Experimental Therapeutics >Glucocorticoid-induced alterations of renal sulfate transport.
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Glucocorticoid-induced alterations of renal sulfate transport.

机译：糖皮质激素诱导的肾脏硫酸盐转运的改变。

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摘要

Glucocorticoid administration decreases renal sodium/phosphate cotransport in the proximal tubule due to a down-regulation of the sodium/phosphate cotransporter but has no effect on the sodium-dependent transport of glucose or proline. The objectives of the present investigation were to determine the effects of the glucocorticoid methylprednisolone (MPL) on 1) inorganic sulfate renal clearance in rats in vivo, 2) sodium/sulfate cotransport in kidney cortex membrane vesicles, and 3) the cellular mechanism of the MPL-induced alterations in sulfate renal transport. Male adrenalectomized Wistar rats received an i.v. dose of 50 mg/kg MPL or the vehicle. Urine samples were collected for 12 h after the administration of MPL, and blood samples were collected at the midpoint of the urine collection. Other animals were sacrificed at 4, 6, and 12 h after MPL administration, and the kidney cortex was removed for RNA or membrane preparations. Kidney cortex sodium/sulfate cotransporter (NaSi-1) mRNA levels were determined by reverse transcription-polymerase chain reaction and NaSi-1 protein levels were determined by enzyme-linked immunosorbent assay. The urinary excretion rate and renal clearance of sulfate were significantly increased in MPL-treated animals (144.0 +/- 27.0 versus 65.3 +/- 21.3 micromol/12 h/kg and 0.208 +/- 0.038 versus 0. 078 +/- 0.025 ml/min/kg, mean +/- S.E., n = 9-12 in treated versus control). The V(max) value for sodium-dependent sulfate transport in brush border membrane vesicles (representing reabsorption in the proximal tubules) was significantly decreased in MPL-treated animals compared with controls (0.68 +/- 0.07 versus 0.88 +/- 0.05 nmol/mg of protein/10 s, mean +/- S.E.). There was no change in the K(m) value for sodium/sulfate cotransport in brush-border membrane and no change in sulfate/anion exchange in basolateral membrane vesicles. Membrane fluidity in brush border membrane and basolateral membrane vesicles, determined by the fluorescence polarization of 1, 6-diphenyl-1,3,5-hexatriene was unaltered by MPL treatment. NaSi-1 mRNA levels were significantly decreased at 4 and 6 h, but not 12 h, after MPL administration, whereas NaSi-1 protein expression was significantly decreased at 4, 6, and 12 h. Therefore, MPL treatment increases the renal clearance of inorganic sulfate, at least in part, due to down-regulation of NaSi-1 mRNA and protein expression in the kidney.
机译：糖皮质激素的给药由于钠/磷酸酯共转运蛋白的下调而减少了近端肾小管中肾脏钠/磷酸酯的共转运，但对葡萄糖或脯氨酸的钠依赖性转运没有影响。本研究的目的是确定糖皮质激素甲基强的松龙（MPL）对1）体内大鼠体内无机硫酸盐肾清除率，2）钠/硫酸钠在肾皮质膜囊泡中共转运的影响以及3）肾小球皮质激素的细胞机制的作用。 MPL诱导的硫酸盐肾脏转运改变。雄性肾上腺切除的Wistar大鼠接受静脉注射。剂量为50 mg / kg MPL或载体。给予MPL后12 h收集尿液样本，并在尿液收集中点收集血液样本。在MPL给药后第4、6和12 h处死其他动物，取出肾皮质用于RNA或膜制备。通过逆转录-聚合酶链反应测定肾脏皮质钠/硫酸盐共转运蛋白（NaSi-1）mRNA水平，并通过酶联免疫吸附测定法测定NaSi-1蛋白水平。经MPL处理的动物的尿液排泄率和硫酸盐的肾脏清除率显着提高（144.0 +/- 27.0对65.3 +/- 21.3 micromol / 12 h / kg和0.208 +/- 0.038对0. 078 +/- 0.025 ml / min / kg，平均+/- SE，治疗组与对照组之间n = 9-12）。与对照组相比，经MPL处理的动物的刷状缘膜囊泡中钠依赖性硫酸盐转运的V（max）值（代表近端小管中的重吸收）显着降低（0.68 +/- 0.07与0.88 +/- 0.05 nmol /毫克蛋白质/ 10秒，平均值+/- SE）。在刷状边界膜中钠/硫酸盐共转运的K（m）值没有变化，在基底外侧膜囊泡中的硫酸盐/阴离子交换没有变化。通过1,6-二苯基-1,3,5-己三烯的荧光偏振确定的刷缘膜和基底外侧膜囊泡中的膜流动性通过MPL处理未改变。在MPL给药后，NaSi-1 mRNA水平在4和6 h显着降低，但在12 h没有降低，而NaSi-1蛋白表达在4、6和12 h显着降低。因此，MPL治疗至少部分归因于NaSi-1 mRNA和肾脏蛋白质表达的下调，从而增加了无机硫酸盐的肾脏清除率。

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