Article

Clinical lessons from the calcium-sensing receptor

Division of Endocrinology, Diabetes and Hypertension at Brigham and Women's Hospital in Boston, MA, USA.
Nature Clinical Practice Endocrinology &#38 Metabolism (Impact Factor: 7.55). 03/2007; 3(2):122-33. DOI: 10.1038/ncpendmet0388
Source: PubMed

ABSTRACT

The extracellular calcium ion (Ca(2+)(e))-sensing receptor (CaR) enables key tissues that maintain Ca(2+)(e) homeostasis to sense changes in the Ca(2+)(e) concentration. These tissues respond to changes in Ca(2+)(e) with functional alterations that will help restore Ca(2+)(e) to normal. For instance, decreases in Ca(2+)(e) act via the CaR to stimulate secretion of parathyroid hormone-a Ca(2+)(e)-elevating hormone-and to increase renal tubular calcium reabsorption; each response helps promote normalization of Ca(2+)(e) levels. Further work is needed to determine whether the CaR regulates other parameters of renal function (e.g. 1,25-dihydroxyvitamin D(3) synthesis, intestinal absorption of mineral ions, and/or bone turnover). Identification of the CaR has also elucidated the pathogenesis and pathophysiology of inherited disorders of mineral and electrolyte metabolism; moreover, acquired abnormalities of Ca(2+)(e)-sensing can result from autoimmunity to the CaR, and reduced CaR expression in the parathyroid may contribute to the abnormal parathyroid secretory control that is observed in primary and secondary hyperparathyroidism. Finally, calcimimetics-allosteric activators of the CaR-treat secondary hyperparathyroidism effectively in end-stage renal failure.

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    • "The role of the calcium-sensing receptor CaSR in the systemic circulation is to sense changes in extracellular Ca 2+ and evoke appropriate counter-regulatory responses to regain normocalcaemia [4]. The functional link between the receptor and regulation of systemic calcium in normal physiology and disease has been extensively studied [4]. However, CaSR expression is not restricted to the cells involved in the control of systemic Ca 2+ [5]. "
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    ABSTRACT: In this study we use a novel approach to quantitatively investigate mechanical and interfacial properties of clonal β-cells using AFM-Single Cell Force Spectroscopy (SCFS). MIN6 cells were incubated for 48hrs with 0.5mM Ca2+ ± the calcimimetic R568 (1μM). AFM-SCFS adhesion and indentation experiments were performed by using modified tipless cantilevers. Hertz contact model was applied to analyse force-displacement (F-d) curves for determining elastic or Young’s modulus (E). Our results show CaSR-evoked increases in cell-to-cell adhesion parameters and E modulus of single cells, demonstrating that cytomechanics have profound effects on cell adhesion characterization.
    Full-text · Article · Apr 2014 · FEBS letters
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    • "The role of the calcium-sensing receptor CaSR in the systemic circulation is to sense changes in extracellular Ca 2+ and evoke appropriate counter-regulatory responses to regain normocalcaemia [4]. The functional link between the receptor and regulation of systemic calcium in normal physiology and disease has been extensively studied [4]. However, CaSR expression is not restricted to the cells involved in the control of systemic Ca 2+ [5]. "
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    ABSTRACT: a b s t r a c t In this study we use a novel approach to quantitatively investigate mechanical and interfacial properties of clonal b-cells using AFM-Single Cell Force Spectroscopy (SCFS). MIN6 cells were incu-bated for 48 h with 0.5 mM Ca 2+ ± the calcimimetic R568 (1 lM). AFM-SCFS adhesion and indentation experiments were performed by using modified tipless cantilevers. Hertz contact model was applied to analyse force–displacement (F–d) curves for determining elastic or Young's modulus (E). Our results show CaSR-evoked increases in cell-to-cell adhesion parameters and E modulus of single cells, demonstrating that cytomechanics have profound effects on cell adhesion characterization. Ó 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
    Full-text · Dataset · Feb 2014
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    • "However, further clinical studies will be needed to validate the efficacy and safety of ATF936 in treating osteoporosis. In addition, calcilytics could be useful for correcting hypocalcemia resulting from increased sensitivity of the CaSR to extracellular calcium[135]. "
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    ABSTRACT: The calcium-sensing receptor (CaSR) belongs to the evolutionarily conserved family of plasma membrane G protein-coupled receptors (GPCRs). Early studies identified an essential role for the CaSR in systemic calcium homeostasis through its ability to sense small changes in circulating calcium concentration and to couple this information to intracellular signaling pathways that influence parathyroid hormone secretion. However, the presence of CaSR protein in tissues not directly involved in regulating mineral ion homeostasis points to a role for the CaSR in other cellular functions including the control of cellular proliferation, differentiation and apoptosis. This position at the crossroads of cellular fate designates the CaSR as an interesting study subject likely to be involved in a variety of previously unconsidered human pathologies, including cancer, atherosclerosis and Alzheimer's disease. Here, we will review the recent discoveries regarding the relevance of CaSR signaling in development and disease. Furthermore, we will discuss the rational for developing and using CaSR-based therapeutics.
    Full-text · Article · Dec 2012 · Current Molecular Medicine
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