IMR Press / FBL / Volume 8 / Issue 6 / DOI: 10.2741/1068

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

The calcium-sensing receptor in human disease
Show Less
1 Endocrine-Hypertension Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical school, 221 longwood avenue, LMRC room 205, Boston, MA 02115, USA
2 Osteoporosis and Bone Metabolic Unit, Department of Clinical Biochemistry and Endocrinology, Copenhagen University Hospital Hvidovre, DK-2650, Denmark
Front. Biosci. (Landmark Ed) 2003, 8(6), 377–390;
Published: 1 May 2003

The discovery of the calcium-sensing receptor (CaR), a G protein–coupled receptor, has led to the elucidation of the pivotal roles of the CaR in systemic calcium homeostasis. The receptor is situated on the chief cells of the parathyroid glands, where it senses the extracellular Ca2+ concentration and in turn alters the rate of secretion of parathyroid hormone (PTH). The intracellular signal pathways to which the CaR couples include, but are not limited to, phospholipase C (PLC), and mitogen-activated protein kinases. The receptor is widely expressed in various tissues and likely serves important cellular functions beyond that of maintaining systemic calcium homeostasis. Functionally important mutations in the receptor have been found to cause disorders in calcium homeostasis due both to changes in the set point for PTH secretion and to the control of renal calcium excretion. These mutations cause hypercalcemia when the mutation inactivates the receptor and cause hypocalcemia when the mutation activates the receptor. Recent studies have revealed the presence of circulating autoantibodies to the calcium-sensing receptor in humans, with the clinical presentation the same as that for diseases caused by mutations in the CaR. In renal secondary hyperparathyroidism, a drug that stimulates the receptor (calcimimetic) shows great promise as a medical treatment for this condition.

familial hypocalciuric hypercalcemia
autosomal Dominant Hypoparathyroidism
Back to top