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New concepts in calcium-sensing receptor pharmacology and signalling

Ward, Donald T. and Riccardi, Daniela 2012. New concepts in calcium-sensing receptor pharmacology and signalling. British Journal of Pharmacology 165 (1) , pp. 35-48. 10.1111/j.1476-5381.2011.01511.x

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The calcium-sensing receptor (CaR) is the key controller of extracellular calcium (Ca2+o) homeostasis via its regulation of parathyroid hormone (PTH) secretion and renal Ca2+ reabsorption. The CaR-selective calcimimetic drug Cinacalcet stimulates the CaR to suppress PTH secretion in chronic kidney disease and represents the world's first clinically available receptor positive allosteric modulator (PAM). Negative CaR allosteric modulators (NAMs), known as calcilytics, can increase PTH secretion and are being investigated as possible bone anabolic treatments against age-related osteoporosis. Here we address the current state of development and clinical use of a series of positive and negative CaR modulators. In addition, clinical CaR mutations and transgenic mice carrying tissue-specific CaR deletions have provided a novel understanding of the relative functional importance of CaR in both calciotropic tissues and those elsewhere in the body. The development of CaR-selective modulators and signalling reagents have provided us with a more detailed appreciation of how the CaR signals in vivo. Thus, both of these areas of CaR research will be reviewed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Nature Publishing Group
ISSN: 0007-1188
Last Modified: 04 Jun 2017 08:05

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