ArticleThe Journal of clinical investigation2012
PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 199 citations in OpenAlex.
- Impact of digital health technology-based nutritional interventions on the nutritional status of hemodialysis patients: a systematic review and meta-analysis.Frontiers in nutrition · 2025Pooled it
- Response of Vitamin D after Magnesium Intervention in a Postmenopausal Population from the Province of Granada, Spain.Nutrients · 2020Trial
- PTH-Independent CaSR Inhibition with the Oral Calcilytic Encaleret Improves Calcium Homeostasis in Post-Surgical Hypoparathyroidism: A Phase 2 Open-Label Proof-of-Concept Trial.Research square · 2026Article
- Article
- Distinct cell types along thick ascending limb express pathways for monovalent and divalent cation transport.JCI insight · 2025Article
- Micro- and Nanoplastics as Disruptors of the Endocrine System-A Review of the Threats and Consequences Associated with Plastic Exposure.International journal of molecular sciences · 2025Review
- Calcium-Sensing Receptor in the Thick Ascending Limb and Renal Response to Hypercalcemia.Journal of the American Society of Nephrology : JASN · 2025Article
- The calcium-sensing receptor: a comprehensive review on its role in calcium homeostasis and therapeutic implications.American journal of translational research · 2025Review
- Paracellular Transport and Renal Tubule Calcium Handling: Emerging Roles in Kidney Stone Disease.Journal of the American Society of Nephrology : JASN · 2024Review
- Ophthalmate is a new regulator of motor functions via CaSR: implications for movement disorders.Brain : a journal of neurology · 2024Article
- Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024Review
- Glutathione-Based Photoaffinity Probe Identifies Caffeine as a Positive Allosteric Modulator of the Calcium-Sensing Receptor.ACS chemical biology · 2024Article
- A novel mouse model for familial hypocalciuric hypercalcemia (FHH1) reveals PTH-dependent and independent CaSR defects.Pflugers Archiv : European journal of physiology · 2024Article
- Claudin-10 Expression and the Gene Expression Pattern of Thick Ascending Limb Cells.International journal of molecular sciences · 2024Article
- How the kidney regulates magnesium: a modelling study.Royal Society open science · 2024Article
- The complex relationship between vitamin D and kidney stones: balance, risks, and prevention strategies.Frontiers in nutrition · 2024Review
- Unlocking the mysteries of n-oxPTH: implications for CKD patients.Frontiers in endocrinology · 2024Review
- Contribution of thick ascending limb and distal convoluted tubule to glucose-induced hypercalciuria in healthy controls.American journal of physiology. Renal physiology · 2023Article
- Immunolocalization of Sphingolipid Catabolism Enzymes along the Nephron: Novel Early Urinary Biomarkers of Renal Damage.International journal of molecular sciences · 2023Article
- Thirty years of the NaCl cotransporter: from cloning to physiology and structure.American journal of physiology. Renal physiology · 2023Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tight regulation of calcium levels is required for many critical biological functions. The Ca2+-sensing receptor (CaSR) expressed by parathyroid cells controls blood calcium concentration by regulating parathyroid hormone (PTH) secretion. However, CaSR is also expressed in other organs, such as the kidney, but the importance of extraparathyroid CaSR in calcium metabolism remains unknown. Here, we investigated the role of extraparathyroid CaSR using thyroparathyroidectomized, PTH-supplemented rats. Chronic inhibition of CaSR selectively increased renal tubular calcium absorption and blood calcium concentration independent of PTH secretion change and without altering intestinal calcium absorption. CaSR inhibition increased blood calcium concentration in animals pretreated with a bisphosphonate, indicating that the increase did not result from release of bone calcium. Kidney CaSR was expressed primarily in the thick ascending limb of the loop of Henle (TAL). As measured by in vitro microperfusion of cortical TAL, CaSR inhibitors increased calcium reabsorption and paracellular pathway permeability but did not change NaCl reabsorption. We conclude that CaSR is a direct determinant of blood calcium concentration, independent of PTH, and modulates renal tubular calcium transport in the TAL via the permeability of the paracellular pathway. These findings suggest that CaSR inhibitors may provide a new specific treatment for disorders related to impaired PTH secretion, such as primary hypoparathyroidism.
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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.