ArticleJournal of the American Society of Nephrology : JASN2014
Renal phosphate wasting in the absence of adenylyl cyclase 6.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Distinct roles of ferric carboxymaltose and ferric derisomaltose on phosphate homeostasis in iron deficiency anemia.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2025Article
- Sex differences in renal acid-base regulation.American journal of physiology. Renal physiology · 2025Article
- Genetic deletion of the kidney sodium/proton exchanger-3 (NHE3) does not alter calcium and phosphate balance due to compensatory responses.Kidney international · 2025Article
- Vitamin DScientific reports · 2024Article
- Physiopathology of Phosphate Disorders.Advances in kidney disease and health · 2023Review
- NHE3 in the thick ascending limb is required for sustained but not acute furosemide-induced urinary acidification.American journal of physiology. Renal physiology · 2022Article
- Enhanced phosphate absorption in intestinal epithelial cell-specific NHE3 knockout mice.Acta physiologica (Oxford, England) · 2022Article
- Mathematical Models of Parathyroid Gland Biology: Complexity and Clinical Use.Frontiers in nephrology · 2022Review
- PF-06869206 is a selective inhibitor of renal PAmerican journal of physiology. Renal physiology · 2020Article
- Article
- Pharmacological Npt2a Inhibition Causes Phosphaturia and Reduces Plasma Phosphate in Mice with Normal and Reduced Kidney Function.Journal of the American Society of Nephrology : JASN · 2019Article
- Adenylyl Cyclase 6 Expression Is Essential for Cholera Toxin-Induced Diarrhea.The Journal of infectious diseases · 2019Article
- Contribution of NHE3 and dietary phosphate to lithium pharmacokinetics.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2019Article
- Adenylyl cyclase 6 is required for maintaining acid-base homeostasis.Clinical science (London, England : 1979) · 2018Article
- The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway.Journal of the American Society of Nephrology : JASN · 2018Article
- Identification of adenylyl cyclase isoforms mediating parathyroid hormone- and calcitonin-stimulated cyclic AMP accumulation in distal tubule cells.BMC nephrology · 2017Article
- Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis.Kidney international · 2017Article
- Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus.JCI insight · 2017Article
- Prolonged Pharmacokinetic and Pharmacodynamic Actions of a Pegylated Parathyroid Hormone (1-34) Peptide Fragment.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- NADPH oxidase 4 deficiency increases tubular cell death during acute ischemic reperfusion injury.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) enhance phosphate excretion by the proximal tubule of the kidney by retrieval of the sodium-dependent phosphate transporters (Npt2a and Npt2c) from the apical plasma membrane. PTH activates adenylyl cyclase (AC) through PTH 1 receptors and stimulates the cAMP/PKA signaling pathway. However, the precise role and isoform(s) of AC in phosphate homeostasis are not known. We report here that mice lacking AC6 (AC6(-/-)) have increased plasma PTH and FGF-23 levels compared with wild-type (WT) mice but comparable plasma phosphate concentrations. Acute activation of the calcium-sensing receptor or feeding a zero phosphate diet almost completely suppressed plasma PTH levels in both AC6(-/-) and WT mice, indicating a secondary cause for hyperparathyroidism. Pharmacologic blockade of FGF receptors resulted in a comparable increase in plasma phosphate between genotypes, whereas urinary phosphate remained significantly higher in AC6(-/-) mice. Compared with WT mice, AC6(-/-) mice had reduced renal Npt2a and Npt2c protein abundance, with approximately 80% of Npt2a residing in lysosomes. WT mice responded to exogenous PTH with redistribution of Npt2a from proximal tubule microvilli to intracellular compartments and lysosomes alongside a PTH-induced dose-response relationship for fractional phosphate excretion and urinary cAMP excretion. These responses were absent in AC6(-/-) mice. In conclusion, AC6 in the proximal tubule modulates cAMP formation, Npt2a trafficking, and urinary phosphate excretion, which are highlighted by renal phosphate wasting in AC6(-/-) mice.
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Registered trials
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