Calcium sensing by endocrine cells.

The elucidation of the structure and function of the Ca2+(o)-sensing receptor (CaR) has provided important insights into the normal control of Ca2+(o) homeostasis, particularly the key role of the receptor in kidney and parathyroid. Further studies are needed to define more clearly the homeostatic role of the CaR in additional tissues, both those that are involved and those that are uninvolved in systemic Ca2+(o) homeostasis. The availability of the cloned CaR has also permitted documentation of the molecular basis of inherited disorders of Ca2+(o) sensing, including those in which the receptor is less and or more sensitive than normal to Ca2+(o). Antibodies to the CaR that either activate it or inactivate it produce syndromes resembling the corresponding genetic diseases. Expression of the receptor is abnormally low in 1 degree and 2 degrees hyperparathyroidism, which could contribute to the defective Ca2+(o) sensing in these conditions. The recent discovery of calcimimetics, which sensitize the CaR to Ca2+(o), has provided what will likely be an effective medical therapy for the secondary/tertiary hyperparathyroidism of end stage renal failure as well as for 1 degree hyperparathyroidism.