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The calcium-sensing receptor

Brown, Edward M., Hebert, Steven C., Riccardi, Daniela and Geibel, John P. 2013. The calcium-sensing receptor. In: Alpern, Robert J., Moe, Orson W. and Caplan, Michael eds. Seldin and Giebisch's The Kidney (Fifth Edition), Vol. 5. Physiology & Pathophysiology, vol. 1-2. Dordrecht: Elsevier, pp. 2187-2224. (10.1016/B978-0-12-381462-3.00063-X)

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Cell surface sensors for extracellular Ca2+ and Mg2+51 provide an important mechanism for the regulation of diverse physiological processes by extracellular divalent mineral ions.53, 190 and 402 These ion sensors function as “calciostats” for Ca2+ and/or Mg2+ that not only regulate divalent mineral metabolism at the level of the whole organism but also control a variety of other cellular processes (e.g., salt and water handing in various epithelia and cell proliferation-differentiation) in terrestrial and aquatic animals, as well as in plants. This chapter will focus on the role of the extracellular calcium-sensing receptor (CaSR) in the mammalian parathyroid, kidney, and other tissues participating in divalent mineral ion homeostasis. The unique properties of the mammalian CaSR include: (1) Having extracellular Ca2+ and Mg2+ as its primary physiological ligands, establishing that ions can function as first messengers. (2) Responding with a millimolar EC50, close to the normal plasma ionized Ca2+ concentration, but several orders of magnitude higher than that for ligands of other G protein–coupled receptors. (3) Possessing a remarkable ability to detect small deviations from the normal ionized calcium concentration of 1.1–1.3 mM, making it an ideal sensor for Ca2+, functioning as a “calciostat.” The identification of inherited disorders due to activating or inactivating mutations of the CaSR, basic research in CaSR biology, the development of CaSR-active compounds (calcimimetics), and the results from clinical trials of calcimimetics have established the biological roles of this receptor in mineral ion homeostasis and have suggested roles of the CaSR in several non-Ca2+ homeostatic processes. The reader is referred to Chapter 65 and other chapters in the section, “Regulation and Disorders of Calcium Homeostasis,” for additional information and background.

Item Type: Book Section
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: extracellular calcium sensing receptor, parathyroid, GI tract, kidney, bone, osteoblast, osteoclast, thick ascending limb, paracellular pathway, transcellular pathway, collecting duct, proximal tubule, parathyroid hormone (PTH), cAMP, phospholipase C, cytosolic calcium concentration, extracellular calcium concentration, ionic strength, aromatic amino acid, calcimimetics, cinacalcet, calcilytics, familial hypocalciuric hypercalcemia, neonatal sever hyperparathyroidism, autosomal dominant hypocalcemia, inactivating CaSR mutation, activating CaSR mutation
Publisher: Elsevier
ISBN: 9780123814623
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Last Modified: 04 Jun 2017 06:10

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