Renal adaptation to dietary phosphate restriction in rats. Interactions with insulin and calcitriol

The present study tested the hypothesis that the influence of dietary phosphate (Pi) on the renal handling of Pi changes during development. We evaluated whether variations in the dietary Pi content would alter the tubular capacity of Pi reabsorption [Max RPi/glomerular filtration rate (GFR)] in immature rats, which have a relatively greater Max RPi/GFR compared with adult rats. Then we examined the response of immature and adult Pi-deprived rats to dietary Pi replenishment. Studies were performed in acutely thyroparathyroidectomized Wistar rats at three different stages of development: immature (3- to 4-wk old), young (6- to 7-wk old), and adult (12- to 13-wk old). Animals were fed either low (0.07%)-, normal (0.7%), or high (1.8%)-phosphate diet (LPD, NPD, and HPD, respectively) for 4 days and were then prepared for renal clearance experiments to determine the Max RPi/GFR. On all dietary regimens, the Max RPi/GFR was highest in immature rats and decreased progressively with age. When fed LPD, immature rats, with an already elevated rate of phosphate transport, displayed a remarkable 68 +/- 13% increase in the Max RPi/GFR (from 5.58 +/- 0.29 to 9.47 +/- 0.76 mumol/ml, P less than 0.01). This was significantly greater than the 38 +/- 3% increase observed in adult rats (from 3.50 +/- 0.18 to 4.81 +/- 0.09 mumol/ml). Conversely, in response to HPD, the decrease in the Max RPi/GFR was smallest in immature rats (-42 +/- 2%) compared with the decrement in either young (-54 +/- 3%) or adult (-61 +/- 6%) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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Renal adaptation to dietary phosphate deprivation: role of proximal tubule brush-border membrane fluidity

AJP Renal Physiology ◽

10.1152/ajprenal.1991.260.5.f613 ◽

1991 ◽

Vol 260 (5) ◽

pp. F613-F618 ◽

Cited By ~ 1

Author(s):

B. S. Levine ◽

K. A. Knibloe ◽

K. Golchini ◽

S. Hashimoto ◽

I. Kurtz

Keyword(s):

Proximal Tubule ◽

Brush Border ◽

Temporal Relationship ◽

Brush Border Membrane ◽

Renal Cortex ◽

Pi Transport ◽

Renal Adaptation ◽

Dietary Phosphate ◽

Pi Deprivation

With dietary phosphate (Pi) restriction, fluidity of renal proximal tubule brush-border membranes (BBM) and Na-dependent Pi transport (Na-Pi) are increased, suggesting that changes in BBM fluidity are critical for adaptation to Pi restriction. To test this hypothesis, the temporal relationship between Na-Pi transport and changes in BBM fluidity was assessed after Pi deprivation in rats. Renal cortex was obtained from rats fed either a 0.03% (-P) or a 0.6% (+P) Pi diet for 4 h or 7 days, and BBM were prepared. Na-Pi uptake by BBM was measured by use of rapid filtration, and BBM fluidity was assessed by use of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). After 4 h on the diets, Na-Pi uptake was 439 +/- 142 (SD) and 984 +/- 184 pmol.mg protein-1.5 s-1 in +P and -P, respectively (P less than 0.01, n, = 8). Na-dependent proline uptake was unchanged. DPH anisotropy and total cholesterol were similar between groups: 0.204 +/- 0.025 and 0.401 +/- 0.047 nmol/mg protein, respectively, in +P and 0.205 +/- 0.015 and 0.392 +/- 0.037 in -P (P greater than 0.05, n = 8-10). After 7 days, Na-Pi uptake was 841 +/- 291 in +P and 2,168 +/- 848 pmol.mg protein-1.5 s-1 in -P, P less than 0.01, n = 8. DPH anisotropy and BBM cholesterol were 0.175 +/- 0.019 and 443 +/- 132 nmol/mg protein, respectively, in +P and 0.162 +/- 0.020 (n = 8) and 341 +/- 128 (n = 3) in -P (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Different effects of arsenate and phosphonoformate on Pi transport adaptation in opossum kidney cells

AJP Cell Physiology ◽

10.1152/ajpcell.00186.2009 ◽

2009 ◽

Vol 297 (3) ◽

pp. C516-C525 ◽

Cited By ~ 21

Author(s):

Ricardo Villa-Bellosta ◽

Víctor Sorribas

Keyword(s):

Rat Kidney ◽

Opossum Kidney ◽

Ok Cells ◽

Opossum Kidney Cells ◽

Competitive Inhibitors ◽

Renal Adaptation ◽

Proximal Tubular ◽

Dietary Phosphate ◽

Definition Of

The main nonhormonal mechanism for controlling inorganic phosphate (Pi) homeostasis is renal adaptation of the proximal tubular Pi transport rate to changes in dietary phosphate content. Opossum kidney (OK) cell line is an in vitro renal model that maintains the ability of renal adaptation to the extracellular Pi concentration. We have studied how two competitive inhibitors of Pi transport, arsenate [As(V)] and phosphonoformate (PFA), affect adaptation to low and high Pi concentrations. OK cells show very high affinity for As(V) (inhibitory constant, Ki 0.12 mM) when compared with the rat kidney. As(V) very efficiently reversed the adaptation of OK cells to low Pi (0.1 mM), whereas PFA induced adaptation similar to 0.1 mM Pi. Adaptation with 2 mM Pi or As(V) was characterized by decreases in the maximal velociy ( Vmax) of Pi transport and an abundance of the NaPi-IIa Pi transporter in the plasma membrane, shown by the protein biotinylation. Conversely, PFA and 0.1 mM Pi increased the Vmax and transporter abundance. Changes in the Vmax were limited to a 50% variation, which was not paralleled by changes in the concentration of Pi or of the inhibitor. OK cells are very sensitive to As(V), but the effects are reversible and noncytotoxic. These effects can be interpreted as As(V) being transported into the cell, thereby mimicking a high Pi concentration. PFA blocks the uptake of Pi but is not transported, and it therefore simulates a low Pi concentration inside the cell. To conclude, a mathematical definition of the adaptation process is reported, thereby explaining the limited changes in Pi transport Vmax.

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Evidence for induction of a phosphate appetite in juvenile rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.4.r1358 ◽

1998 ◽

Vol 275 (4) ◽

pp. R1358-R1365 ◽

Cited By ~ 10

Author(s):

Joseph M. Sweeny ◽

H. Edward Seibert ◽

Craig Woda ◽

Jay Schulkin ◽

Aviad Haramati ◽

...

Keyword(s):

Wistar Rats ◽

Tap Water ◽

Potassium Phosphate ◽

Additional Mechanism ◽

Marked Rise ◽

Juvenile Rats ◽

Renal Adaptation ◽

Unrestricted Access ◽

Dietary Phosphate ◽

Unlimited Access

This study examined whether dietary phosphate (Pi) restriction stimulates an appetite for Pi in the juvenile rat, which normally has a high metabolic Pi demand for growth. Juvenile Wistar rats were placed in individual cages with unrestricted access to tap water and a low (LPD, 0.02% Pi) or normal Pi diet (NPD, 0.6% Pi) for 7 days. On day 8, both groups of rats were given unlimited access to a solution of 0.3 M potassium phosphate water (PiH2O) for 8 additional days. Rats fed LPD consumed 70–100% more PiH2O then those rats fed NPD ( P < 0.001). The increase in PiH2O intake resulted in a marked rise in the growth rate of rats fed LPD during days 8–15. A similar Pi intake was inducible after only 2 days of LPD and was associated with significant reductions in both plasma and cerebrospinal fluid (CSF) Pi levels; these levels remained low throughout Pi restriction, despite a significant PiH2O intake. Furthermore, the renal adaptation to enhance Pi reabsorption (TmPi) during Pi deprivation remained elevated despite enhanced PiH2O intake. Replenishment with a high-Pi diet rapidly quenched the PiH2O appetite and was associated with restoration of both plasma and CSF Pi levels. These findings suggest that an appetite for Pi can be induced in juvenile rats, perhaps through lowered plasma and CSF Pi levels. This behavioral response may serve as an additional mechanism to maintain an adequate supply of Pi necessary for growth and development of the animal.

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