Clinical lessons from the calcium-sensing receptor

Publisher Website
Google Scholar
Abstract
In the parathyroid gland, in thyroid C-cells and in many other tissues, the calcium-sensing receptor (CaR) plays a crucial role in calcium homeostasis. The molecular basis of several diseases resulting from abnormalities in the CaR has been characterized; this has provided the framework for the development of pharmacologic CaR activators for clinical use. The extracellular calcium ion (Ca2+e)-sensing receptor (CaR) enables key tissues that maintain Ca2+e homeostasis to sense changes in the Ca2+e concentration. These tissues respond to changes in Ca2+e with functional alterations that will help restore Ca2+e to normal. For instance, decreases in Ca2+e act via the CaR to stimulate secretion of parathyroid hormone—a Ca2+e-elevating hormone—and to increase renal tubular calcium reabsorption; each response helps promote normalization of Ca2+e levels. Further work is needed to determine whether the CaR regulates other parameters of renal function (e.g. 1,25-dihydroxyvitamin D3 synthesis, intestinal absorption of mineral ions, and/or bone turnover). Identification of the CaR has also elucidated the pathogenesis and pathophysiology of inherited disorders of mineral and electrolyte metabolism; moreover, acquired abnormalities of Ca2+e-sensing can result from autoimmunity to the CaR, and reduced CaR expression in the parathyroid may contribute to the abnormal parathyroid secretory control that is observed in primary and secondary hyperparathyroidism. Finally, calcimimetics—allosteric activators of the CaR—treat secondary hyperparathyroidism effectively in end-stage renal failure.

This publication has 72 references indexed in Scilit: