Phosphate transport in brush border membrane vesicles isolated from renal cortex of young growing and adult rats

Caverzasio, Joseph; Murer, Heini; Fleisch, H.; Bonjour, J.-P.

doi:10.1007/bf00589094

Cited by 32 publications

(12 citation statements)

References 24 publications

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“…We also show that Npt2 -/-mice fail to exhibit an increase in BBM Na + /Pi cotransport in response to Pi deprivation, thereby documenting the crucial role of Npt2 in the renal adaptive response to low Pi intake. Previous studies have provided evidence for higher Na + /Pi cotransport activity in BBMs from younger animals when compared with older animals, consistent with the notion that the requirement for Pi is increased during growth (30,31,38). Although it was suggested that the higher transport activity observed in weanling rats, relative to 3-month-old rats, is mediated by a Na + /Pi cotransporter that is distinct from, but related to, Npt2 (30), this growth-related Na + /Pi cotransporter has not yet been identified at the molecular level.…”

supporting

confidence: 73%

Effects of Npt2 gene ablation and low-phosphate diet on renal Na+/phosphate cotransport and cotransporter gene expression

Hoag¹,

Martel²,

Gauthier³

et al. 1999

J. Clin. Invest.

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The renal Na + /phosphate (Pi) cotransporter Npt2 is expressed in the brush border membrane (BBM) of proximal tubular cells. We examined the effect of Npt2 gene knockout on age-dependent BBM Na + /Pi cotransport, expression of Na + /Pi cotransporter genes Npt1, Glvr-1, and Ram-1, and the adaptive response to chronic Pi deprivation. Na + /Pi cotransport declines with age in wild-type mice (Npt2 +/+ ), but not in mice homozygous for the disrupted Npt2 allele (Npt2 -/-). At all ages, Na + /Pi cotransport in Npt2 -/-mice is approximately 15% of that in Npt2 +/+ littermates. Only Npt1 mRNA abundance increases with age in Npt2 +/+ mice, whereas Npt1, Glvr-1, and Ram-1 mRNAs show an age-dependent increase in Npt2 -/-mice. Pi deprivation significantly increases Na + /Pi cotransport, Npt2 protein, and mRNA in Npt2 +/+ mice. In contrast, Pi-deprived Npt2 -/-mice fail to show the adaptive increase in transport despite exhibiting a fall in serum Pi. We conclude that (a) Npt2 is a major determinant of BBM Na + /Pi cotransport; (b) the age-dependent increase in Npt1, Glvr-1, and Ram-1 mRNAs in Npt2 -/-mice is insufficient to compensate for loss of Npt2; and (c) Npt2 is essential for the adaptive BBM Na + /Pi cotransport response to Pi deprivation.

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supporting

confidence: 73%

Effects of Npt2 gene ablation and low-phosphate diet on renal Na+/phosphate cotransport and cotransporter gene expression

Hoag¹,

Martel²,

Gauthier³

et al. 1999

J. Clin. Invest.

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“…The limited capacity of senescent animals to adapt to a hypophosphatemic environment (Caverzasio et al, 1982a;Kiebzak and Sacktor, 1986) was retained by the cultured renal cells in the present study. We showed that renal cells respond to a 24-hour phosphate deprivation by increasing phosphate uptake by 46% and 24% of their corresponding controls in young and adult cell preparations, respectively.…”

Section: Discussionmentioning

confidence: 81%

Sodium‐dependent phosphate transport in primary cultures of renal tubule cells from young and adult rats

Chen

King

Armbrecht

1990

Journal Cellular Physiology

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The transport of phosphate by primary cultures of renal cells from young (5-6 weeks) and adult (10-12 months) rats was studied. Renal tubule cells isolated from young and adult groups exhibited typical epithelial morphology and similar growth rates. The Na-dependent phosphate uptake was saturable with a Km of 5-7 microM over a substrate range of 1-500 microM. A decrease in Na-dependent phosphate uptake in adult cells (30%) was found compared to that of young cells. The Na-independent component of phosphate uptake did not vary with age. In addition, the inhibition of phosphate uptake by a variety of compounds (ouabain, gramicidin, 2,4-dinitrophenol, KCN, and arsenate) were similar in both age groups. Kinetic analysis showed that a significant reduction in Vmax (4.4 +/- 0.4 vs. 3.1 +/- 0.2 nmol Pi/mg protein/10 min in young and adult cells, respectively), but not Km, resulted in this decreased uptake of phosphate in adult groups. There was no difference in the efflux of phosphate from both age groups. When cells were preincubated in a phosphate-free medium for 24 hours, the uptake of phosphate was increased to 46% and 24% of their corresponding controls in young and adult cells, respectively. The decreased phosphate uptake and limited adaptation to a phosphate-free medium by the adult renal cells may account for the hypophosphatemia and phosphaturia seen in adult and old animals in vivo.

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“…The Pi uptake by preparations of BBM vesicles shows that the PCT PiR is regulated by the Pi content of the diet during the 3rd postnatal wk, as it is in older growing rats and adult rats (7,(27)(28)(29)(30). The initial rate of intravesicular accumulation was higher in LPD than in NPD rats and lower in HPD rats.…”

Section: Animalsmentioning

confidence: 89%

“…This might be compared to the hypercalciuria observed in the Pi depletion of premature infants fed human milk (26). The greater sensitivity of young growing rats to an LPD compared to adult animals (6,7,27) may be attributed to the fact that, for a given Pi deprivation, Pi depletion is much greater in these young growing animals. Lastly, the slight hypomagnesemia of LPD rats, without the increase in the FE of this ion that normally occurs in Pi depletion, suggests that these rats were also suffering from magnesium depletion.…”

Section: Animalsmentioning

confidence: 99%

Effects of an Early Weaning on Phosphate Transport Maturation in the Rat Kidney: Influence of the Phosphate Content of the Diet

et al. 1992

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ABSTRACT. The renal phosphate (Pi) transport system matures during the 3rd postnatal wk in the rat by an increase in the carrier affinity for sodium-cotransported phosphate. This study examines the ability of pups to adapt their renal Pi transport to the dietary phosphorus content during this period of carrier affinity maturation, corresponding to the weaning period in the rat. Clearance experiments and brush border membrane studies were performed on 21-d-old rats weaned early on d 16 onto a low phosphate diet (LPD, 0.19 g/100 g), a normal phosphate diet (control, 0.78 g/100 g), or a high phosphate diet (HPD, 1.5 g/100 g). In LPD rats, the Pi fractional excretion (0.3 f 0.1%) was lower than in controls (18 f 3%, p < 0.001). It remained very low (0.21 f 0.05% in LPD rats versus 40.5 2 6.3% in controls, p < 0.001) after Pi perfusion (1.5 pmol.min-'. 100 g-') and the reabsorbed Pi per min, corrected for the glomerular filtration rate. was higher than in the two othergroups. The calcium fractional excretion (12.6 2 1.02%) in the LPD rats was much higher than in the controls (0.42 2 0.2%, p < 0.001). In contrast, HPD rats had an elevated Pi fractional excretion (41 f 4%, p < 0.001), whereas reabsorbed phosphate per min corrected for the glomerular filtration rate was not increased by a Pi load. The membrane vesicles from 21-dold LPD rats had a higher V,,, (1 1 466 2 1 840 pmol. mg protein-'.I0 s-') than the controls (7 019 f 1 112 pmol. mg protein-'. 10 s-', p < 0.01), whereas those from HPD rats had a lower V,,, (5 161 2 956,p < 0.01). The apparent Km values were unchanged. The LPD rats had high plasma calcium levels. The parathyroid hormone level was depressed by this hypercalcemia 121.97 2 1.9 pg/mL (2.31 f 0.2 pmol/L) in LPD and 38.54 f 2.01 pg/mL (4.05 2 0.21 pmol/L) in normal Pi diet rats, n = 8, p < 0.001j. This plus their LPD explains the lower Pi fractional excretion of these rats and the low Pi V,,, in their brush border membrane. The plasma parathyroid hormonal level of HPD rats was normal (35.07 f 2.23 pg/mL (3.69 f 0.23 pmol/L), n = 81. We conclude that the young 3-wk-old rat can adapt its renal Pi transport capacity to the dietary phosphorus content during the weaning period by varying the number of functional units of the sodium Pi cotransporter or by increasing its turnover rate. Changing the Pi content of the diet induces no apparent change in Pi transport maturation during this period, as there was no change in the carrier affinity. (Pediatr Res 32: 704-709, 1992)

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Phosphate transport in brush border membrane vesicles isolated from renal cortex of young growing and adult rats

Cited by 32 publications

References 24 publications

Effects of Npt2 gene ablation and low-phosphate diet on renal Na+/phosphate cotransport and cotransporter gene expression

Effects of Npt2 gene ablation and low-phosphate diet on renal Na+/phosphate cotransport and cotransporter gene expression

Sodium‐dependent phosphate transport in primary cultures of renal tubule cells from young and adult rats

Effects of an Early Weaning on Phosphate Transport Maturation in the Rat Kidney: Influence of the Phosphate Content of the Diet

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