Bielesz Bernhard, Bacic Desa, Honegger Katharina, Biber Jürg, Murer Heini, Wagner Carsten A
Institute of Physiology and Center for Integrative Human Physiology (CIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Pflugers Arch. 2006 Sep;452(6):683-9. doi: 10.1007/s00424-006-0087-0. Epub 2006 May 19.
Renal phosphate excretion is subjected to circadian rhythmicity. The bulk of filtered inorganic phosphate (P(i)) is reabsorbed by the sodium-dependent phosphate cotransporter NaPi-IIa. The regulation of proximal tubular phosphate reabsorptive capacity is largely attributed to the altered abundance of NaPi-IIa residing in the brush border membrane (BBM) of proximal tubular cells. Therefore, we examined if the diurnal rise in renal phosphate excretion is accompanied by a corresponding change in NaPi-IIa expression. Renal phosphate excretion, creatinine clearance, and serum phosphate were determined at consecutive time points in rats, starting from 8 a.m. until 5 p.m. During this period, renal phosphate excretion (fractional P(i) excretion) increased more than eightfold until 5 p.m. compared to the morning values at 8 a.m. In addition, serum phosphate and creatinine clearance as well as the calculated tubular phosphate threshold increased. Neither immunoblot analysis of BBMs nor immunohistochemical staining for NaPi-IIa yielded evidence for a lower abundance of NaPi-IIa in kidneys collected in the afternoon compared to those in the morning. However, kidneys sampled in the afternoon showed a small decrease (14%) in (32)P uptakes into BBM vesicles (BBMVs). Thus, the diurnal rise in renal phosphate excretion was associated with a mild reduction in the sodium-dependent phosphate transport rate in proximal tubular BBMs. There was no apparent downregulation of NaPi-IIa abundance and only a small reduction in Na(+)-dependent Pi-transport activity. Thus, the diurnal changes in urinary phosphate excretion appear to be mainly related to changes in serum phosphate and tubular threshold but not to NaPi-IIa expression.
肾脏磷酸盐排泄呈现昼夜节律性。大部分滤过的无机磷酸盐（P(i)）通过钠依赖性磷酸盐共转运体NaPi-IIa被重吸收。近端肾小管磷酸盐重吸收能力的调节很大程度上归因于近端肾小管细胞刷状缘膜（BBM）中NaPi-IIa丰度的改变。因此，我们研究了肾脏磷酸盐排泄的昼夜升高是否伴随着NaPi-IIa表达的相应变化。从上午8点到下午5点，在大鼠的连续时间点测定肾脏磷酸盐排泄、肌酐清除率和血清磷酸盐。在此期间，与上午8点的早晨值相比，直到下午5点肾脏磷酸盐排泄（分数P(i)排泄）增加了八倍多。此外，血清磷酸盐、肌酐清除率以及计算出的肾小管磷酸盐阈值均升高。无论是对BBM进行免疫印迹分析还是对NaPi-IIa进行免疫组织化学染色，均未发现下午采集的肾脏中NaPi-IIa的丰度低于上午采集的肾脏。然而，下午采集的肾脏显示BBM囊泡（BBMVs）对(32)P的摄取略有下降（14%）。因此，肾脏磷酸盐排泄的昼夜升高与近端肾小管BBM中钠依赖性磷酸盐转运速率的轻度降低有关。NaPi-IIa丰度没有明显下调，仅Na(+)依赖性Pi转运活性略有降低。因此，尿磷酸盐排泄的昼夜变化似乎主要与血清磷酸盐和肾小管阈值的变化有关，而与NaPi-IIa表达无关。
