title: Unchanged expression of the sodium-dependent phosphate cotransporter NaPi-IIa despite diurnal changes in renal phosphate excretion.
abstract: 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.
authors.affiliation: Institute of Physiology and Center for Integrative Human Physiology (CIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bielesz
authors.forename: Desa
authors.initials: D
authors.lastname: Bacic
authors.forename: Katharina
authors.initials: K
authors.lastname: Honegger
authors.forename: Jürg
authors.initials: J
authors.lastname: Biber
authors.forename: Heini
authors.initials: H
authors.lastname: Murer
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
mesh_terms: D000465:Algorithms; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology; D010710:Phosphates / Q000652:urine*; D016226:Phosphorus, Dietary / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000096:biosynthesis*
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D016226:Phosphorus, Dietary; C493556:Slc34a1 protein, rat; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D012964:Sodium