ArticleNature communications2019
Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
What it found
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Who cites it
125 citing papers in PubMed, 229 citations in OpenAlex.
- Phosphate homeostasis and endocrine regulators.Pediatric nephrology (Berlin, Germany) · 2026Review
- FGF23 - A hormone produced by bone and has many faces.Reviews in endocrine & metabolic disorders · 2026Review
- Validation and Clinical Evaluation of an LC-MS/MS Method for Serum Full-Length Parathyroid Hormone 1-84 with Application to Chronic Kidney Disease.ACS pharmacology & translational science · 2026Article
- Hypophosphatasia: Results of a Country-Wide Selective Screening Program Using NGS Technology as a First-Tier Test.International journal of molecular sciences · 2026Article
- Molecular mechanism of p-Coumaric acid in the regulation of AQP2 function through the activation of calcium-sensing receptor signaling.Scientific reports · 2026Article
- Review
- Article
- Impact of Clinoptilolite and Anionic Salts on Calcium Homeostasis, Parathyroid Hormone, and Related Metabolic Parameters in Periparturient Dairy Cows.Veterinary sciences · 2026Article
- Cardioprotective Role of CalhexCell biochemistry and biophysics · 2026Review
- Effects of Gender, Menopause, Vitamin D Status, and Tumor Parathyroid Cell Activity on Serum Phosphate Levels in a Large Cohort of Patients with Sporadic Hypercalcemic Primary Hyperparathyroidism.International journal of molecular sciences · 2026Article
- The Impact of Hyperphosphatemia on Mineral and Bone Metabolism: Implications for Bone and Vascular Health.International journal of molecular sciences · 2026Review
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- Hemorrhagic fever with renal syndrome complicated by reversible secondary hyperparathyroidism during renal recovery: a case report.Frontiers in medicine · 2026Article
- Celastrol Attenuates FGF23 Expression in Osteoblasts by Inhibiting STAT3 Activation.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Combination therapy with nutritional vitamin D and calcimimetics in secondary hyperparathyroidism: a mechanism-based approach to restoring PTH regulation.Frontiers in nutrition · 2026Review
- Phosphate and Inflammation in Health and Kidney Disease.International journal of molecular sciences · 2025Review
- Current Controversies on Adequate Circulating Vitamin D Levels in CKD.International journal of molecular sciences · 2025Review
- Predictors of Hungry Bone Syndrome After Parathyroidectomy in Secondary Hyperparathyroidism: A Narrative Review of Bone Turnover Biomarkers and Risk Prediction Tools.Journal of clinical medicine · 2025Review
- Correlation between parathyroid volume and calcium and phosphorus metabolism in maintenance hemodialysis patients based on Doppler ultrasound technology.International urology and nephrology · 2025Article
- Hungry Bone Syndrome After Parathyroidectomy for Secondary Hyperparathyroidism: Pathogenesis and Contemporary Clinical Considerations.Journal of clinical medicine · 2025Review
65 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). However, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration, the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.