Effect of dietary phosphate intake on phosphate transport by isolated rat renal brush-border vesicles

Stoll, R; Kinne, Rolf; Murer, Heini

doi:10.1042/bj1800465

Cited by 97 publications

(35 citation statements)

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“…Moreover, shorter time points than 4 hrs were not investigated. The adaption to chronic Pi restriction intact in thyroparathyroidectomized rats demonstrating that neither PTH nor thyroid hormone are the major regulator in this setting [53,62]. Despite changes in PTH levels, the abundance of the PTH receptor 1 in the brush border membrane as well as in total kidney remained stable.…”

Section: Napi-iia Is Upregulated Despite Persistently High Fgf23 Levelmentioning

confidence: 95%

The phosphate transporter NaPi-IIa determines the rapid renal adaptation to dietary phosphate intake in mouse irrespective of persistently high FGF23 levels

Capuano

Stange

Mühlemann

et al. 2013

Pflugers Arch - Eur J Physiol

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Renal reabsorption of inorganic phosphate (Pi) is mediated by the phosphate transporters NaPi-IIa, NaPi-IIc, and Pit-2 in the proximal tubule brush border membrane (BBM). Dietary Pi intake regulates these transporters; however, the contribution of the specific isoforms to the rapid and slow phase is not fully clarified. Moreover, the regulation of PTH and FGF23, two major phosphaturic hormones, during the adaptive phase has not been correlated. C57/BL6 and NaPi-IIa(-/-) mice received 5 days either 1.2 % (HPD) or 0.1 % (LPD) Pi-containing diets. Thereafter, some mice were acutely switched to LPD or HPD. Plasma Pi concentrations were similar under chronic diets, but lower when mice were acutely switched to LPD. Urinary Pi excretion was similar in C57/BL6 and NaPi-IIa(-/-) mice under HPD. During chronic LPD, NaPi-IIa(-/-) mice lost phosphate in urine compensated by higher intestinal Pi absorption. During the acute HPD-to-LPD switch, NaPi-IIa(-/-) mice exhibited a delayed decrease in urinary Pi excretion. PTH was acutely regulated by low dietary Pi intake. FGF23 did not respond to low Pi intake within 8 h whereas the phospho-adaptator protein FRS2 necessary for FGF-receptor cell signaling was downregulated. BBM Pi transport activity and NaPi-IIa but not NaPi-IIc and Pit-2 abundance acutely adapted to diets in C57/BL6 mice. In NaPi-IIa(-/-), Pi transport activity was low and did not adapt. Thus, NaPi-IIa mediates the fast adaptation to Pi intake and is upregulated during the adaptation to low Pi despite persistently high FGF23 levels. The sensitivity to FGF23 may be regulated by adapting FRS2 abundance and phosphorylation. ABSTRACTRenal reabsorption of inorganic phosphate (Pi) is mediated by the phosphate transporters, NaPi-IIa, NaPi-IIc, and Pit-2 in the proximal tubule brush border membrane (BBM). Dietary Pi intake regulates these transporters, however, the contribution of the specific isoforms to the rapid and slow phase are not fully clarified.Moreover, the regulation of PTH and FGF23, two major phosphaturic hormones, during the adaptive phase has not been correlated. C57/BL6 and NaPi-IIa -/-mice received 5 days either 1.2 % (HPD) or 0.1% (LPD) Pi containing diets. Thereafter, some mice were acutely switched to LPD or HPD. Plasma Pi concentrations were similar under chronic diets, but lower when mice were acutely switched to LPD.Urinary Pi excretion was similar in C57/BL6 and NaPi-IIa -/-mice under HPD. During chronic LPD, NaPi-IIa -/-mice lost phosphate in urine compensated by higher intestinal Pi absorption. During the acute HPD-to-LPD switch, NaPi-IIa -/-mice exhibited a delayed decrease in urinary Pi excretion. PTH was acutely regulated by low dietary Pi intake. FGF23 did not respond to low Pi intake within 8 hours whereas the phosphoadaptator protein FRS2α necessary for FGF-receptor cell signaling was downregulated. BBM Pi transport activity and NaPi-IIa but not NaPi-IIc and Pit-2 abundance acutely adapted to diets in C57/BL6 mice. In NaPi-IIa -/-Pi transport activity was low and did not adapt. Th...

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Section: Napi-iia Is Upregulated Despite Persistently High Fgf23 Levelmentioning

confidence: 95%

The phosphate transporter NaPi-IIa determines the rapid renal adaptation to dietary phosphate intake in mouse irrespective of persistently high FGF23 levels

Capuano

Stange

Mühlemann

et al. 2013

Pflugers Arch - Eur J Physiol

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“…The transport rate of phosphate into BBMV was determined at 90 s and 90 min (equilibrium value) as described (17,29) at 25°C in the presence of inward gradients of 100 mM NaCl or 100 mM KCl and 0.1 mM K2HPO4.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Intestinal Phosphate Transport II. Metabolic acidosis stimulates Na⁺-dependent phosphate absorption and expression of the Na⁺-P_i cotransporter NaPi-IIb in small intestine

Stauber¹,

Radanovic²,

Stange³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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During metabolic acidosis, P i serves as an important buffer to remove protons from the body. Pi is released from bone together with carbonate buffering protons in blood. In addition, in the kidney, the fractional excretion of phosphate is increased allowing for the excretion of more acid equivalents in urine. The role of intestinal P i absorption in providing Pi to buffer protons and compensating for loss from bone during metabolic acidosis has not been clarified yet. Inducing metabolic acidosis (NH 4Cl in drinking water) for 2 or 7 days in mice increased urinary fractional P i excretion twofold, whereas serum Pi levels were not altered. Na ϩ -dependent Pi transport in the small intestine, however, was stimulated from 1.89 Ϯ 3.22 to 40.72 Ϯ 11.98 pmol/mg protein (2 days of NH 4Cl) in brush-border membrane vesicles prepared from total small intestine. Similarly, the protein abundance of the Na ϩ -dependent phosphate cotransporter NaPi-IIb in the brush-border membrane was increased 5.3-fold, whereas mRNA levels remained stable. According to immunohistochemistry and real-time PCR NaPi-IIb expression was found to be mainly confined to the ileum in the small intestine, and this distribution was not altered during metabolic acidosis. These results suggest that the stimulation of intestinal P i absorption during metabolic acidosis may contribute to the buffering of acid equivalents by providing phosphate and may also help to prevent excessive liberation of phosphate from bone. phosphate SEVERAL MECHANISMS CONTRIBUTE to the buffering and elimination of excessive protons and acid equivalents during metabolic acidosis. Besides respiration, increased release of buffer substances from bone and stimulated reabsorption of bicarbonate and increased excretion of protons by the kidneys are the major mechanisms to restore acid-base balance (11, 16). Excretion of protons by the kidney requires so called titratable acids, i.e., ammonia, citrate, and phosphate, buffering protons in urine in the collecting duct and thus increasing the maximal acid excretion rate (16). The renal excretion of ammonia and phosphate is highly increased during metabolic acidosis, whereas excretion of citrate is decreased (3). Ammonia (NH 3 ) is synthetized from glutamine metabolism in the kidney proximal tubule in response to metabolic acidosis (27). In addition, it is thought that inhibition of renal reabsorption of phosphate contributes mainly to increased phosphate excretion (1). In a rat model for metabolic acidosis, a decrease in mRNA and protein of the major Na ϩ -P i cotransporter NaPi-IIa as well as in Na ϩ -dependent P i uptake into brush border membrane (BBM) vesicles (BBMV) has been found (1). Systemic P i levels are only slightly decreased during metabolic acidosis, an effect that has been attributed to the acid-stimulated release of P i from bone together with Ca 2ϩ and carbonate (23). Indeed, the release of phosphate from bone during short-and long-term metabolic acidosis in in vivo and in in vitro models has been extensively documented a...

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“…32 P into brush-border membrane vesicles (BBMV) were performed according to the filtration technique as already described (36). In brief, aliquots of vesicles were incubated for 1 min in three different solutions: 0 mM Na ϩ , 100 mM Na ϩ , and 100 mM Na ϩ plus 6 mM PFA.…”

Section: Uptakes Of 32 P and D-[ 3 H]glucose Into Renal Brush-border mentioning

confidence: 99%

Renal-specific and inducible depletion of NaPi-IIc/Slc34a3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice

Myakala

Motta

Murer

et al. 2014

American Journal of Physiology-Renal Physiology

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. Renal-specific and inducible depletion of NaPi-IIc/Slc34a3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice. Am J Physiol Renal Physiol 306: F833-F843, 2014. First published February 19, 2014 doi:10.1152/ajprenal.00133.2013.-The proximal renal epithelia express three different Na-dependent inorganic phosphate (Pi) cotransporters: NaPi-IIa/SLC34A1, NaPi-IIc/ SLC34A3, and PiT2/SLC20A2. Constitutive mouse knockout models of NaPi-IIa and NaPi-IIc suggested that NaPi-IIa mediates the bulk of renal reabsorption of P i whereas the contribution of NaPi-IIc to this process is minor and probably restricted to young mice. However, many reports indicate that mutations of NaPi-IIc in humans lead to hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report the generation of a kidney-specific and inducible NaPi-IIc-deficient mouse model based on the loxP-Cre system. We found that the specific removal of the cotransporter from the kidneys of young mice does not impair the capacity of the renal epithelia to transport Pi. Moreover, the levels of Pi in plasma and urine as well as the circulating levels of parathyroid hormone, FGF-23, and vitamin D3 remained unchanged. These findings are in agreement with the data obtained with the constitutive knockout model and suggest that, under steady-state conditions of normal dietary P i, NaPi-IIc is not an essential Na-Pi cotransporter in murine kidneys. However, and unlike the constitutive mutants, the kidney-specific depletion of NaPi-IIc does not result in alteration of the homeostasis of calcium. This suggests that the calcium-related phenotype observed in constitutive knockout mice may not be related to inactivation of the cotransporter in kidney. phosphate homeostasis; epithelial transport; renal proximal tubules; SLC34 cotransporters INORGANIC PHOSPHATE (P I ) IS an essential anion that is required for a wide variety of molecular and cellular processes. In mammals, the concentration of P i in plasma remains within a relative tightly controlled range (0.8 -1.4 mM in humans). This control is executed by organs responsible for P i absorption/ excretion (intestine and kidneys), P i storage (bones), as well as production and secretion of regulatory factors (kidneys, bones, and parathyroid glands; for a review, see Ref. 5). However, the final control of P i homeostasis depends on the kidneys as they can adjust the urinary excretion of the anion to the body's specific requirements. The importance of the kidney in this process is highlighted by the deleterious consequences of both renal wasting and retention of the anion. Thus renal loss of P i leads primarily to skeletal deformities whereas hyperphosphatemia is implicated in vascular calcification and mortality in end-stage kidney disease (for a review, see Ref.2). The renal epithelia express at least three Na-dependent P i cotransporters: NaPi-IIa/SLC34A1, NaPi-IIc/SLC34A3, and PiT2/SLC20A2 (for a review, see Ref. 14). These cotransporters are expressed in the brush-borde...

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Effect of dietary phosphate intake on phosphate transport by isolated rat renal brush-border vesicles

Cited by 97 publications

References 16 publications

The phosphate transporter NaPi-IIa determines the rapid renal adaptation to dietary phosphate intake in mouse irrespective of persistently high FGF23 levels

The phosphate transporter NaPi-IIa determines the rapid renal adaptation to dietary phosphate intake in mouse irrespective of persistently high FGF23 levels

Regulation of Intestinal Phosphate Transport II. Metabolic acidosis stimulates Na⁺-dependent phosphate absorption and expression of the Na⁺-P_i cotransporter NaPi-IIb in small intestine

Renal-specific and inducible depletion of NaPi-IIc/Slc34a3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice

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Effect of dietary phosphate intake on phosphate transport by isolated rat renal brush-border vesicles

Cited by 97 publications

References 16 publications

The phosphate transporter NaPi-IIa determines the rapid renal adaptation to dietary phosphate intake in mouse irrespective of persistently high FGF23 levels

The phosphate transporter NaPi-IIa determines the rapid renal adaptation to dietary phosphate intake in mouse irrespective of persistently high FGF23 levels

Regulation of Intestinal Phosphate Transport II. Metabolic acidosis stimulates Na+-dependent phosphate absorption and expression of the Na+-Pi cotransporter NaPi-IIb in small intestine

Renal-specific and inducible depletion of NaPi-IIc/Slc34a3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice

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Regulation of Intestinal Phosphate Transport II. Metabolic acidosis stimulates Na⁺-dependent phosphate absorption and expression of the Na⁺-P_i cotransporter NaPi-IIb in small intestine