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Int Rev Cell Mol Biol. 2016;327:321-369. doi: 10.1016/bs.ircmb.2016.05.004. Epub 2016 Jun 25.

The Calcium-Sensing Receptor in Health and Disease.

Author information

1
Endocrinology and Nutrition, Valladolid University Hospital, Valladolid, Spain.
2
Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, Valladolid, Spain; Institute of Molecular Biology and Genetics (IBGM), University of Valladolid and National Research Council (CSIC), Valladolid, Spain.
3
Institute of Molecular Biology and Genetics (IBGM), University of Valladolid and National Research Council (CSIC), Valladolid, Spain.
4
Institute of Molecular Biology and Genetics (IBGM), University of Valladolid and National Research Council (CSIC), Valladolid, Spain. Electronic address: carlosv@ibgm.uva.es.

Abstract

The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca2+ and by other physiological cations including Mg2+, amino acids, and polyamines. CaSR is the most important master controller of the extracellular Ca2+ homeostatic system being expressed at high levels in the parathyroid gland, kidney, gut and bone, where it regulates parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca2+ absorption and resorption, respectively. Gain and loss of function mutations in the CaSR are responsible for severe disturbances in extracellular Ca2+ metabolism. CaSR agonists (calcimimetics) and antagonists (calcilytics) are in use or under intense research for treatment of hyperparathyroidism secondary to kidney failure and hypocalcemia with hypercalciuria, respectively. Expression of the CaSR extends to other tissues and systems beyond the extracellular Ca2+ homeostatic system including the cardiovascular system, the airways, and the nervous system where it may play physiological functions yet to be fully understood. As a consequence, CaSR has been recently involved in different pathologies including uncontrolled blood pressure, vascular calcification, asthma, and Alzheimer's disease. Finally, the CaSR has been shown to play a critical role in cancer either contributing to bone metastasis and/or acting as a tumor suppressor in some forms of cancer (parathyroid cancer, colon cancer, and neuroblastoma) and as oncogene in others (breast and prostate cancers). Here we review the role of CaSR in health and disease in calciotropic tissues and others beyond the extracellular calcium homeostatic system.

KEYWORDS:

Alzheimer's disease; asthma; calcium; calcium-sensing receptor; cancer; cardiovascular disease; hyperparathyroidism

PMID:
27692178
DOI:
10.1016/bs.ircmb.2016.05.004
[Indexed for MEDLINE]

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