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  • Title: Role of calcium-sensing receptor in mineral ion metabolism and inherited disorders of calcium-sensing.
    Author: Chattopadhyay N, Brown EM.
    Journal: Mol Genet Metab; 2006 Nov; 89(3):189-202. PubMed ID: 16919492.
    Abstract:
    The extracellular calcium-sensing receptor (CaR), a G protein-coupled receptor that resides on the parathyroid cell surface negatively regulates secretion of parathyroid hormone (PTH). The CaR is functionally expressed in bone, kidney, and gut--the three major calcium-translocating organs involved in calcium homeostasis. Further studies are needed to define fully the homeostatic roles of the CaR in tissues that are involved in systemic extracellular calcium [Ca(2+)](o) homeostasis. The role of the CaR in regulating calcium metabolism has been greatly clarified by the identification and studies of genetically determined disorders that either activate or inactivate the receptor. Antibodies to the CaR that either activate or inactivate it produce syndromes resembling the corresponding genetic diseases. Expression of the CaR is significantly reduced in primary and secondary hyperparathyroidism, which could contribute to the defective [Ca(2+)](o)-sensing in these conditions. Calcimimetics act as CaR agonists or allosteric activators and thereby potentiate the effects of [Ca(2+)](o) on parathyroid cell function. This kind of pharmacological manipulation of the CaR is now used for the treatment of hyperparathyroid states, whereby the calcimimetics increase the activation of the CaR at any given level of extracellular calcium. Calcimimetics are also an effective element in the treatment of secondary hyperparathyroidism, particularly in dialysis patients, by virtue of reducing plasma levels of PTH, calcium and phosphate.
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