Effect of phosphate deprivation on phosphate reabsorption in rat nephron: role of PTH

Abstract

The sites of enhanced phosphate (PO4) reabsorption after PO4 deprivation were investigated before and after infusion of parathyroid hormone (PTH) in acutely thyroparathyroidectomized rats. Animals were fed either a control PO4 diet (1.6% P) or a low PO4 diet (0.025% P) for 2 days or 7-10 days. In control rats, PTH decreased PO4 reabsorption in the proximal tubule, loop of Henle, and distal convolution. PO4 reabsorption in the proximal tubule was enhanced after 2 days of PO4 deprivation. In this group, proximal PO4 reabsorption was decreased by PTH but remained greater than in control rats (70 +/- 6 vs. 45 +/- 6 pmol/min; P less than 0.025). After PTH, PO4 reabsorption increased in the loop of Henle from 3 +/- 0.5 to 13 +/- 2 pmol/min (P less than 0.005), whereas it was unaltered in the distal convolution in PO4-deprived rats. PTH markedly increased fractional excretion of PO4 in control rats but not in PO4-deprived rats. After prolonged PO4 deprivation, PO4 reabsorption along the nephron was unaltered by PTH. These results demonstrate that acute PO4 deprivation enhances PO4 reabsorption in the proximal tubule, although the phosphaturic effect of PTH in this segment is not abolished. Resistance to the inhibitory effect of PTH on PO4 reabsorption in some portion of the loop of Henle and possibly also in the distal convolution accounts for the absence of a significant phosphaturic effect of the hormone in acutely PO4-deprived rats. Prolongation of PO4 deprivation results in unresponsiveness to PTH extending to the proximal tubule.

Defective PTH regulation of sodium-dependent phosphate transport in NHERF-1−/−renal proximal tubule cells and wild-type cells adapted to low-phosphate media

“…Animals fed a low-phosphate diet have been reported to have a blunted phosphaturic response to PTH (23,29,36). To determine whether this response was intrinsic to the cells, wild-type cells were incubated in low-phosphate media (0.3 mM phosphate) for 24 h. Our prior studies indicated that the adaptation to low-phosphate media is complete by 24 h. Sodiumindependent phosphate transport did not differ between wildtype proximal tubule cells grown in DMEM/F-12 (0.39 Ϯ 0.09 and 0.34 Ϯ 0.08 nmol⅐mg protein Ϫ1 ⅐10 min Ϫ1 in the absence or presence of PTH, respectively) and wild-type cells grown in low-phosphate media (0.32 Ϯ 0.06 and 0.39 Ϯ 0.10 nmol⅐mg protein Ϫ1 ⅐10 min Ϫ1 in the absence or presence of PTH, respectively).…”

“…Several prior studies in intact animals have indicated that the phosphaturic effect of PTH is blunted in animals adapted to a low-phosphate diet (23,29,36). The mechanism of this relative resistance to the phosphaturic effect of PTH is unknown but may be the result of specific biochemical changes in renal proximal tubule cells or changes in systemic factors that alter PTH signaling.…”

“…The second goal of the present experiments was to determine the effect of PTH on phosphate transport in proximal tubule cells from wild-type mice adapted to growth in low-phosphate media. A number of prior studies in intact animals have suggested that adaptation to a low-phosphate diet decreases the phosphaturic effect of PTH (23,29,36). The mechanism of this response is unknown but may reflect increased trafficking of Npt2a to the apical membrane in response to phosphate restriction (3, 18).…”

Prevention of Enhanced Parathyroid Hormone Secretion, Synthesis and Hyperplasia by Mild Dietary Phosphorus Restriction in Early Chronic Renal Failure in Rats: Possible Direct Role of Phosphorus

“…1). Since such changes in urine are the hallmarks of dietary phos phorus restriction [19][20][21], we considered 0.3% phospho rus diet to be a phosphorus-restricted diet. 243 Serum immunoreactive PTH level in chronic renal failure rats was increased to 34.2 ± 2.83 pg/ml compared with that of sham-operated rats (24.0 ± 1.08 pg/ml) when fed with 0.6% phosphorus diet ( fig.…”

Renal tubular sites of increased phosphate transport and NaPi-2 expression in the juvenile rat

“…In addition, the PTH-stimulated increase in urinary P i excretion is blunted in P i -deprived animals (3,26,31,34). Both in vivo and in vitro studies in the adult animal have demonstrated that this adaptive increase in P i uptake is due to enhanced P i reabsorption within both the proximal convoluted tubules (PCT) (20,21,29,37,41) and segments beyond the PCT, most likely the proximal straight tubule (PST) (15,29,34,41). Furthermore, dietary P i deprivation in the adult animal is also associated with an increase in the maximal velocity (V max ) of apical brush-border membrane (BBM) sodium-dependent P i cotransport (NaPi) activity (4,18,20,21,24,25).…”