The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases

The Ca -sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and β-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid...

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Bibliographic Details
Published in:	Nature reviews. Endocrinology 2019-01, Vol.15 (1), p.33-51
Main Authors:	Hannan, Fadil M, Kallay, Enikö, Chang, Wenhan, Brandi, Maria Luisa, Thakker, Rajesh V
Format:	Article
Language:	eng
Subjects:	Arrestin Asthma Brain injury Breast cancer Breastfeeding & lactation Calcimimetic Agents - therapeutic use Calcium (urinary) Calcium homeostasis Calcium ions Calcium metabolism disorders Calcium-sensing receptors Cardiovascular diseases Cell receptors Cell surface Cellular signal transduction Colorectal carcinoma Development and progression Drug development Excretion Female Gene Expression Regulation Genetic aspects Genetic Predisposition to Disease - epidemiology Health aspects Homeostasis Hormones Humans Hypercalcemia Hypercalcemia - congenital Hypercalcemia - drug therapy Hypercalcemia - genetics Hypercalcemia - physiopathology Hypercalciuria - drug therapy Hypercalciuria - genetics Hypercalciuria - physiopathology Hyperparathyroidism Hypocalcemia Hypocalcemia - drug therapy Hypocalcemia - genetics Hypocalcemia - physiopathology Hypoparathyroidism - congenital Hypoparathyroidism - drug therapy Hypoparathyroidism - genetics Hypoparathyroidism - physiopathology Incidence Insulin Lactation Male Medical research Medicine, Experimental Metabolic regulation Metabolism Mutation Mutation - genetics Nephrolithiasis - drug therapy Nephrolithiasis - genetics Nephrolithiasis - physiopathology Nervous system diseases Neuroblastoma Neurological diseases Parathyroid Parathyroid hormone Physiological aspects Prognosis Prostate Receptors, Calcium-Sensing - drug effects Receptors, Calcium-Sensing - genetics Risk Assessment Secretion Therapeutic applications Treatment Outcome Wound healing
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Summary:	The Ca -sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and β-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid hormone secretion, urinary Ca excretion, skeletal development and lactation. The importance of the CaSR for these calcitropic processes is highlighted by loss-of-function and gain-of-function CaSR mutations that cause familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, respectively, and also by the fact that alterations in parathyroid CaSR expression contribute to the pathogenesis of primary and secondary hyperparathyroidism. Moreover, the CaSR is an established therapeutic target for hyperparathyroid disorders. The CaSR is also expressed in organs not involved in Ca homeostasis: it has noncalcitropic roles in lung and neuronal development, vascular tone, gastrointestinal nutrient sensing, wound healing and secretion of insulin and enteroendocrine hormones. Furthermore, the abnormal expression or function of the CaSR is implicated in cardiovascular and neurological diseases, as well as in asthma, and the CaSR is reported to protect against colorectal cancer and neuroblastoma but increase the malignant potential of prostate and breast cancers.
ISSN:	1759-5029 1759-5037