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Calcium Signalling and Disease pp 139–167Cite as

The Calcium-Sensing Receptor: Physiology, Pathophysiology and Car-Based Therapeutics

Physiology and pathophysiology of CaR

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 45))

Abstract

The extracellular calcium (Ca2+_o)-sensing receptor (CaR) enables the parathyroid glands and other CaR-expressing cells to sense alterations in the level of Ca2+_o and to respond with changes in function that are directed at normalizing the blood calcium concentration. In addition to the parathyroid gland, the kidney is a key site for Ca2+_o-sensing that enables it to make physiologically relevant alterations in divalent cation and water metabolism. Several disorders of Ca2+_o-sensing arise from inherited or acquired abnormalities that “reset” the serum calcium concentration upward or downward. Inactivating mutations produce a benign form of hypercalcemia when present in the heterozygous state, termed Familial Hypocalciuric Hypercalcemia (FHH), while homozygous mutations produce a much more severe hypercalcemic disorder resulting from marked hyperparathyroidism, called Neonatal Severe Hyperparathyroidism (NSHPT). Activating mutations cause a hypocalcemic syndrome of varying severity, termed autosomal dominant hypocalcemia or hypoparathyroidism. Inactivating or activating antibodies directed at the CaR produce the expected hyper- or hypocalcemic syndromes, respectively. “Calcimimetic” CaR activators and “calcilytic” CaR antagonists have been developed. The calcimimetics are currently in use for controlling severe hyperparathyroidism in patients receiving dialysis treatment for end stage renal disease or with parathyroid cancer. Calcilytics are being evaluated as a means of inducing a “pulse” in the circulating parathyroid hormone (PTH) concentration, which would mimic that resulting from injection of PTH, an established anabolic form of treatment for osteoporosis

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  1. Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 221 Longwood Avenue, 02115 Boston, MA, USA

    E.M. BROWN (M.D)

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  1. University of Padova, Padova, Italy

    Ernesto Carafoli

  2. University of Padova, Padova, Italy

    Marisa Brini

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BROWN, E. (2007). The Calcium-Sensing Receptor: Physiology, Pathophysiology and Car-Based Therapeutics. In: Carafoli, E., Brini, M. (eds) Calcium Signalling and Disease. Subcellular Biochemistry, vol 45. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6191-2_6

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