Mechanism of glucocorticoid effect on renal transport of phosphate.
Mechanism of glucocorticoid effect on renal transport of phosphate.
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糖皮质激素影响磷酸盐肾脏转运的机制。
DOI：
10.1152/ajpcell.1982.243.5.c227
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Dousa,TP
中科院分区：
文献类型：
--
作者：
Turner,ST;Kiebzak,GM;Dousa,TP
我们探讨了是否糖皮质激素的管理，一个已知的刺激肾再生（GNG），可以减少贪婪的无机磷（Pi）重吸收稳定在低磷饮食（LPD）的大鼠。大鼠适应LPD注射糖皮质激素（GCD）曲安奈德（1.25或2.5毫克100克体重-1.day-1 ip）2天，他们表现出了深刻的增加，在注射期间尿中排泄的Pi。在清除率研究中，GCD增加了Pi的清除率和排泄分数，但没有改变Pi的滤过负荷。与对照组大鼠相比，GCD处理大鼠肾皮质制备的管腔刷状缘膜（BBM）囊泡对32 Pi的初始“上坡”Na+梯度（Nao+大于Nai+）依赖性摄取显著降低（大于40%）;对D-[3 H]葡萄糖的Na+梯度依赖性摄取没有减少。在“平衡”的时间间隔，在120分钟测量，BBM囊泡从控制和GCD治疗的大鼠没有不同的摄取32 Pi或D-[3 H]葡萄糖。动力学分析表明，GCD处理大鼠的BBM显示初始Na+依赖性~（32）Pi摄取的最大速度（Vmax）显著降低（-40%），但BBM转运系统对Pi的表观亲和力（表观Km = 0.078 mM Pi）与对照组无差异。与对照组相比，GCD治疗组大鼠BBM的碱性磷酸酶比活性低得多（-40%），但其他三种BBM酶（麦芽糖酶、亮氨酸氨肽酶和γ-谷氨酰转移酶）的活性没有差异。此外，在体外的BBM的曲安西龙没有影响的Na+依赖性摄取的32 Pi或碱性磷酸酶活性。GCD处理的大鼠适应LPD的皮质切片中，α-酮戊二酸的GNG率显著增加。此外，在GCD治疗大鼠的肾皮质中，NAD+与NADH的比率较高，尽管NAD [NAD+ + NADH]的总含量与对照组没有差异。肾排泄，BBM和代谢变化引起的控制。肾排泄，BBM，GCD治疗引起的代谢变化是相似的完整和甲状腺甲状旁腺切除大鼠。在通过体内给予GCD喂食LPD的大鼠中引起的磷酸盐尿似乎至少部分是由于近端小管的管腔BBM的能力降低，近端小管的管腔BBM的Na+依赖性摄取Pi的能力降低。虽然观察到的参数之间的因果关系尚未建立，但我们的结果与肾GNG率的增加的解释是一致的，这可能是通过NAD+对BBM的作用（J. Clin. Invest. 67：1347-1360，1981），降低近端小管中Pi的管腔摄取和重吸收。
We explored whether glucocorticoid administration, a known stimulus of renal gluconeogenesis (GNG), could decrease avid inorganic phosphate (Pi) reabsorption in rats stabilized on low-phosphorus diet (LPD). Rats adapted to LPD were injected with the glucocorticoid (GCD) triamcinolone acetonide (1.25 or 2.5 mg.100 g body wt-1.day-1 ip) for 2 days; they showed a profound increase in urinary excretion of Pi during the injection period. In clearance studies GCD increased the clearance and fractional excretion of Pi but did not change the filtered load of Pi. Initial "uphill" Na+-gradient (Nao+ greater than Nai+)-dependent uptake of 32Pi by luminal brush-border membrane (BBM) vesicles prepared from renal cortex of rats treated with GCD was markedly (greater than 40%) decreased compared with control rats; Na+-gradient-dependent uptake of D-[3H]glucose was not diminished. At the "equilibrium" time interval, measured at 120 min, BBM vesicles from control and GCD-treated rats did not differ in the uptake of 32Pi or D-[3H]glucose. With kinetic analysis, BBM from GCD-treated rats showed a marked decrease (-40%) in the maximum velocity (Vmax) of initial Na+-dependent 32Pi uptake, but the apparent affinity of the BBM transport system for Pi (apparent Km = 0.078 mM Pi) was not different from that of controls. Alkaline phosphatase specific activity was much lower (-40%) in BBM from GCD-treated rats compared with controls, but the activities of three other BBM enzymes (maltase, leucine aminopeptidase, and gamma-glutamyl transferase) were not different. The addition of triamcinolone to BBM in vitro had no effect on either Na+-dependent uptake of 32Pi or alkaline phosphatase activity. The rate of GNG from alpha-ketoglutarate was significantly increased in cortical slices from GCD-treated rats adapted to LPD. Also, the NAD+-to-NADH ratio was higher in the renal cortex of GCD-treated rats, although the total content of NAD [NAD+ + NADH] was not different from controls. Renal excretory, BBM, and metabolic changes elicited controls. Renal excretory, BBM, and metabolic changes elicited by GCD treatment were similar in intact and thyroparathyroidectomized rats. Phosphaturia elicited in rats fed LPD by GCD administration in vivo appears to be at least in part due to a decreased capacity of luminal BBM of proximal tubules for decreased capacity of luminal BBM of proximal tubules for Na+-dependent uptake of Pi. Although the causal relationship between observed parameters is not established, our results are compatible with the interpretation that an increase in the rate of renal GNG, perhaps via action of NAD+ on BBM (J. Clin. Invest. 67: 1347-1360, 1981), decreases luminal uptake and reabsorption of Pi in proximal tubules.