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Article Type

Original Study

Abstract

This is a study of calcium-sensing receptors (CaSR), biology, and clinical significance. The CaSR plays an essential role in the regulation of extracellular calcium (Ca 2+ ) homeostasis. CaSR is expressed in all tissues related to this control (parathyroid glands, thyroid C cells, kidneys, intestine, and bones) and also in tissues with apparently no role in the maintenance of extracellular Ca 2+ levels, such as the brain, skin, and pancreas. CaSR cloning was immediately followed by the association of genetic human diseases with inactivating and activating CaSR mutations: Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are caused by CaSR-inactivating mutations, whereas autosomal dominant hypoparathyroidism is secondary to CaSR-activating mutations. Study of CaSR functions aided the development of drugs that modify their functions either by stimulation (calcimimetic drugs) or by inhibition (calcilytic drugs). CaSR plays a major role in the maintenance of a physiological serum Ca 2+ concentration. There are a number of inherited and acquired conditions in which the level of expression and/or function of the CaSR are altered. Also, there are drugs that modify the function of calcium-sensing receptors (CaSR-based therapeutics).

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