The calcium-sensing receptor

Ranieri, Marianna, Shepelmann, Martin, Riccardi, Daniela ORCID: https://orcid.org/0000-0002-7322-3163, Valenti, Giovanna and Geibel, John P. 2026. The calcium-sensing receptor. Alpern, Robert J., Caplan, Michael J., Moe, Orson W. and Quaggin, Susan E., eds. Seldin and Giebisch's The Kidney: Physiology and Pathophysiology (Sixth Edition), Elsevier, pp. 1987-2033. (10.1016/b978-0-12-815389-5.00028-9)

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Abstract

Cell surface sensors for extracellular Ca2+ and Mg2+ provide an important mechanism for the regulation of diverse physiological processes by extracellular divalent mineral ions. These ion sensors function as “thermostats” 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 CaSR is a member of the G protein–coupled receptor (GPCR) superfamily discovered in 1993 by Brown and coworkers. It comprises 612 amino acids and is followed by a 250 amino acid transmembrane domain (TMD) of seven alpha-helices that span cell membrane and, finally, by a carboxy-terminal (C) tail of approximately 200 amino acids. 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 GPCRs; and (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.

Item Type:	Book Section
Date Type:	Publication
Status:	Published
Schools:	Schools > Biosciences
Publisher:	Elsevier
ISBN:	9780128153895
Last Modified:	18 May 2026 10:31
URI:	https://orca.cardiff.ac.uk/id/eprint/187054

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