Effects of dietary Pi on the renal Na+-dependent Pi transporter NaPi-2 in thyroparathyroidectomized rats

Takahashi, Fumie; Morita, Kyoko; Katai, Kanako; Segawa, Hiroko; Fujioka, Ai; Kouda, Tomoko; Tatsumi, Sawako; Nii, Tomoko; Taketani, Yutaka; Haga, Hiromi; Hisano, Setsuji; Fukui, Yoshihiro; Miyamoto, Ken‐ichi; Takeda, Eiji

doi:10.1042/bj3330175

Cited by 50 publications

(31 citation statements)

References 26 publications

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“…An important regulator of Ca and P homeostasis is the activation of 1,25(OH) 2 D 3 by CYP27B1 in the kidney. The expression of CYP27B1 has been shown to be regulated by dietary P, PTH, and 1,25(OH) 2 D 3 (Gonzalez and Martin, 1996;Takahashi et al, 1998;Kawane et al, 2001;Mulroney et al, 2004). With the greater circulating concentrations of 1,25(OH) 2 D 3 observed among our PD animals, it was not surprising that we observed a similar increase in renal expression of CYP27B1 mRNA.…”

Section: Discussionsupporting

confidence: 65%

“…Although this has not been reported previously, a possible explanation for the increased expression is that the suppression of PTHR expression by PTH (Gonzalez and Martin, 1996;Kawane et al, 2001) would likely not take place with the very low concentrations of circulating PTH seen at the end of this study. In addition to increases in the message for CYP27B1, levels of NPT2 mRNA have been shown to be dramatically increased during P deficiency (Takahashi et al, 1998;Mulroney et al, 2004). We did not see an increase in the expression of this gene based on dietary P restriction.…”

Section: Discussionmentioning

confidence: 99%

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Response to dietary phosphorus deficiency is affected by genetic background in growing pigs1

Alexander

Cutler

et al. 2008

Journal of Animal Science

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Concern over the environmental effect of P excretion from pig production has led to reduced dietary P supplementation. To examine how genetics influence P utilization, 94 gilts sired by 2 genetic lines (PIC337 and PIC280) were housed individually and fed either a P-adequate diet (PA) or a 20% P-deficient diet (PD) for 14 wk. Initially and monthly, blood samples were collected and BW recorded after an overnight fast. Growth performance and plasma indicators of P status were determined monthly. At the end of the trial, carcass traits, meat quality, bone strength, and ash percentage were determined. Pigs fed the PD diet had decreased (P < 0.05) plasma P concentrations and poorer G:F (P < 0.05) over the length of the trial. After 4 wk on trial, pigs fed the PD diet had increased (P < 0.05) plasma 1,25(OH) 2 D 3 and decreased (P < 0.05) plasma parathyroid hormone compared with those fed the PA diet. At the end of the trial, pigs fed the PD diet had decreased (P < 0.05) BW, HCW, and percentage fat-free lean and tended to have decreased LM area (P = 0.06) and marbling (P= 0.09) and greater (P = 0.12) 10th-rib backfat than pigs fed the PA diet. Additionally, animals fed the PD diet had weaker bones and also decreased (P < 0.05) ash percentage and increased (P < 0.05) concentrations of 1α-hydroxylase and parathyroid hormone receptor mRNA in kidney tissue. Regardless of dietary treatment, PIC337-sired pigs consumed more feed and gained more BW than their PIC280-sired counterparts (P < 0.05) during the study. The PIC337-sired pigs also had greater (P < 0.05) HCW, larger (P < 0.01) LM area, and tended to have (P = 0.07) greater dressing percentage. Meat from the PIC337-sired pigs also tended to have greater (P = 0.12) concentrations of lactate but decreased (P = 0.07) concentrations of total glucose units 24 h postslaughter. Although plasma 1,25(OH) 2 D 3 concentrations were elevated (P < 0.05) in all the animals fed the PD diet, this elevation due to P deficiency tended (P = 0.09) to be greater in the PIC337-sired pigs after 12 wk on the treatment. The PIC337-sired pigs had stronger (P < 0.01) bones with greater ash percentage than the PIC280-sired pigs. The difference in the strength of the radii between the PIC337-sired pigs fed the PA and PD diets was greater than their PIC280-sired counterparts, which resulted in sire line × treatment interactions (P < 0.05). These data indicate differing mechanisms of P utilization between these genetic lines. Elucidating these mechanisms may lead to strategies to increase efficiency of growth in a more environmentally friendly manner. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. ABSTRACT: Concern over the environmental effect of P excretion from pig production has led to reduced dietary P supplementation. To examine how genetics influence P utilization, 94 gilts sired by 2 genetic lines (PIC337 and PIC280) were housed individually and fed either a...

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Response to dietary phosphorus deficiency is affected by genetic background in growing pigs1

Alexander

Cutler

et al. 2008

Journal of Animal Science

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“…The protocols for these studies were approved by the Animal Experimentation Committee of Tokushima University. The effect of PTH on regulation of type IIc Na-P i cotransporter in TPTX rats was investigated after intravenous administration of bovine PTH (amino acid 1-34; Sigma) at a dose of 7.5 g/100 g body wt under anesthesia (14,27).…”

Section: Animals and Dietsmentioning

confidence: 99%

Parathyroid hormone-dependent endocytosis of renal type IIc Na-P_icotransporter

Segawa¹,

Yamanaka²,

Onitsuka³

et al. 2007

American Journal of Physiology-Renal Physiology

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128

105

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Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of the renal type IIc Na-Pi cotransporter gene, suggesting that the type IIc transporter plays a prominent role in renal phosphate handling. The goal of the present study was to investigate the regulation of the type IIc Na-Pi cotransporter by parathyroid hormone (PTH). Type IIc Na-Pi cotransporter levels were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours after administration of PTH, type IIc transporter protein levels were markedly decreased in the apical membrane fraction but recovered to baseline levels at 24 h. Immunohistochemical analyses demonstrated the presence of the type IIc transporter in the apical membrane and subapical compartments in the proximal tubular cells in TPTX animals. After administration of PTH, the intensity of immunoreactive signals in apical and subapical type IIc transporter decreased in the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the internalization of the type IIc transporter. In addition, leupeptin prevented the PTH-mediated degradation of the type IIa transporter in lysosomes but had no effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH-treated TPTX rats, the internalization of the type IIc transporter occurred after administration of PTH(1-34) (PKA and PKC activator) or PTH(3-34) (PKC activator). Thus the present study demonstrated that PTH is a major hormonal regulator of the type IIc Na-Pi cotransporter in renal proximal tubules. phosphate transporter; proximal tubule; regulation INORGANIC PHOSPHATE (P i ) reabsorption in the renal proximal tubule is required for body P i homeostasis, and Na ϩ -dependent P i (Na-P i ) transporters in the brush-border membrane (BBM) of proximal tubular cells mediate the rate-limiting step in the overall P i -reabsorptive process (17, 19 -21). The type IIa and type IIc Na-P i cotransporters are expressed in the apical membrane of proximal tubular cells and mediate Na-P i cotransport, and the extent of P i reabsorption in the proximal tubules is determined largely by the abundance of the type IIa Na-P i cotransporter (17, 19 -21, 28). Indeed, Na-P i cotransporter type IIa-deficient mice (Npt2a Ϫ/Ϫ mice) exhibit increased urinary P i excretion, hypophosphatemia, and an appropriate adaptive increase in the circulating concentration of 1,25(OH) 2 D 3 (2, 28). Additional biochemical findings in Npt2aϪ/Ϫ mice include hypercalcemia, hypercalciuria, decreased serum parathyroid hormone (PTH) levels, and elevated serum alkaline phosphatase activity (2, 28). These biochemical features are typical of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a Mendelian disorder of renal P i reabsorption (6, 30). However, in contrast to patients with HHRH, Npt2a Ϫ/Ϫ mice do not exhibit rickets and osteomalacia (2, 7, 28), and linkage analyses indicated that the Npt2a gene is not a candidate for HHRH patients (9, 33).More recently, two groups demonstrated that HHRH results f...

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“…The changes in PTH levels were achieved within at least 4 hrs after switching to high Pi intake and within less than 2 hrs after ingesting low phosphate diets. Previous experiments in thyroparathyroidectomized rats showed that adaption from high to low Pi diet did not increase NaPi-IIa abundance within 4 hrs whereas switching from low to high Pi reduced NaPi-IIa protein after 4 hrs [55]. Since animals were not substituted with thyroid hormone no conclusions on the adaption from high to low Pi diets can be made.…”

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

confidence: 94%

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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Effects of dietary Pi on the renal Na+-dependent Pi transporter NaPi-2 in thyroparathyroidectomized rats

Cited by 50 publications

References 26 publications

Response to dietary phosphorus deficiency is affected by genetic background in growing pigs1

Response to dietary phosphorus deficiency is affected by genetic background in growing pigs1

Parathyroid hormone-dependent endocytosis of renal type IIc Na-P_icotransporter

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

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Effects of dietary Pi on the renal Na+-dependent Pi transporter NaPi-2 in thyroparathyroidectomized rats

Cited by 50 publications

References 26 publications

Response to dietary phosphorus deficiency is affected by genetic background in growing pigs1

Response to dietary phosphorus deficiency is affected by genetic background in growing pigs1

Parathyroid hormone-dependent endocytosis of renal type IIc Na-Picotransporter

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

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Parathyroid hormone-dependent endocytosis of renal type IIc Na-P_icotransporter