Relationship between Phosphaturia and Acute Hypercapnia in the Rat

Webb, Rhonda; Woodhall, Philip B.; Tisher, C. Craig; Glaubiger, George A.; Neelon, Frank A.; Robinson, Roscoe R.

doi:10.1172/jci108837

Cited by 28 publications

(3 citation statements)

References 45 publications

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“…69,70 We also observed a brisk increase in phosphate excretion during the alkaline challenge, which gradually returned towards baseline during subsequent acidic load (Figure 5C). Phosphaturia during alkalosis is in line with previous observations in rats, 38,[43][44][45][46] dogs, 37,39,40 and humans. 41,42 The underlying mechanism is not exactly clear.…”

Section: Response To Dynamic Acid-base Challengesupporting

confidence: 91%

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Two‐pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling

et al. 2023

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Aim Two‐pore channels (TPCs) constitute a small family of cation channels expressed in endo‐lysosomal compartments. TPCs have been characterized as critical elements controlling Ca2+‐mediated vesicular membrane fusion and thereby regulating endo‐lysosomal vesicle trafficking. Exo‐ and endocytotic trafficking and lysosomal degradation are major mechanisms of adaption of epithelial transport. A prime example of highly regulated epithelial transport is the tubular system of the kidney. We therefore studied the localization of TPC protein 1 (TPC1) in the kidney and its functional role in the dynamic regulation of tubular transport. Methods Immunohistochemistry in combination with tubular markers were used to investigate TPC1 expression in proximal and distal tubules. The excretion of phosphate and ammonium, as well as urine volume and pH were studied in vivo, in response to dynamic challenges induced by bolus injection of parathyroid hormone or acid–base transitions via consecutive infusion of NaCl, Na2CO3, and NH4Cl. Results In TPC1‐deficient mice, the PTH‐induced rise in phosphate excretion was prolonged and exaggerated, and its recovery delayed in comparison with wildtype littermates. In the acid–base transition experiment, TPC1‐deficient mice showed an identical rise in phosphate excretion in response to Na2CO3 compared with wildtypes, but a delayed NH4Cl‐induced recovery. Ammonium‐excretion decreased with Na2CO3, and increased with NH4Cl, but without differences between genotypes. Conclusions We conclude that TPC1 is expressed subapically in the proximal but not distal tubule and plays an important role in the dynamic adaptation of proximal tubular phosphate reabsorption towards enhanced, but not reduced absorption.

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Section: Response To Dynamic Acid-base Challengesupporting

confidence: 91%

“…Function and apical expression of NHE3 is augmented during acidosis and diminished during alkalosis 24,25 . In contrast, expression of NaPiIIa and phosphate reabsorption are reduced during acidosis leading to phosphaturia, 17,25 while alkalosis is also associated with phosphaturia 37–46 …”

Section: Discussionmentioning

confidence: 99%

Two‐pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling

et al. 2023

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“…If phosphate is transported as H2POï , at higher luminal pH levels, secreted H+ would be utilized primarily for titration of H C 03 [10], with the result that phosphate would remain predominantly in the HPOj form, and only small amounts of H2POj would be available for transport. Finally, acute ele vation of blood P C 0 2 during respiratory aci dosis has been shown to inhibit renal phos phate reabsorption independent of PTH or volume expansion [26], Although the mech anism of the P C 0 2 effect has not been eluci dated, it is possible that N aH C03 infusion raises renal cortical P C 02 markedly [8], and phosphate reabsorption is inhibited as a re sult. Further studies are needed to examine these various hypotheses.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Proximal Tubule Total CO<sub>2</sub> and Phosphate Reabsorption in Acute and Chronic PTX Rats

Kuroda¹,

Aynedjian²,

Zilenovski³

et al. 1978

Kidney Blood Press Res

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The effect of NaHCO₃ infusion on phosphate reabsorption by the proximal convoluted tubule was studied in acute and chronic PTX rats. Either hypertonic NaHCO₃ or NaCl was infused intravenously. Proximal fluid and phosphate reabsorption were measured with ³H-inulin and ³²PO₄, respectively. In acute PTX rats, the fraction of filtered ³²PO₄remaining in the proximal lumen was 5.9% during NaCl infusion and 23% during NaHCO₃infusion (p < 0.001). In the chronic PTX rats, the fraction of filtered ³²PO₄ remaining in the proximal lumen was 24% during NaCl infusion and 38% during NaHCO₂ infusion (p < 0.001). Phosphate reabsorption per unit GFR was reduced by NaHCO₂infusion in both acute and chronic PTX rats. A linear relationship was found between tubular fluid total CO₂ and the fraction of ³²PO₄ remaining in the tubular lumen. The findings indicate that NaHCO₃ infusion inhibits phosphate reabsorption in the proximal convoluted tubule by a mechanism not dependent on PTH or volume expansion, but apparently correlated with intraluminal CO₂.

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Phosphate Homeostasis

Dennis¹

1992

Comprehensive Physiology

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The sections in this article are: Phosphate Regulation Plasma Phosphate Concentration Renal Handling of Phosphate Ulfrafilterability of Plasma Phosphate Localization and Direction of Phosphate Transport Heterogeneity of Phosphate Transport Rates Secretion of Phosphate Cellular Mechanisms of Phosphate Transport Phosphate Entry Phosphate Exit Intracellular Conditions Intracellular Mediators and Regulators of Phosphate Transport Interactions between Phosphate Transport and Cellular Metabolism Metabolic Requirement for Inorganic Phosphate Regulation of Phosphate Excretion Dietary Adaptation Parathyroid Hormone Vitamin D Metabolites Thyroid Hormone Calcitonin Somatotropin (Growth Hormone) Insulin Catecholamines Atrial Natriuretic Peptides Vasopressin Glucagon Glucocorticoids Nonhormonal Factors Affecting Phosphate Metabolic Acidosis Respiratory Alkalosis Hypercapnea Extracellular Volume Expansion Influence of Calcium on Phosphate Excretion

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Relationship between Phosphaturia and Acute Hypercapnia in the Rat

Abstract: A B S T R A C T Standard clearance

Cited by 28 publications

References 45 publications

Two‐pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling

Two‐pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling

Relationship between Proximal Tubule Total CO<sub>2</sub> and Phosphate Reabsorption in Acute and Chronic PTX Rats

Phosphate Homeostasis

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