Role of the calcium-sensing receptor in extracellular calcium homeostasis

Maintaining a constant level of blood Ca2+ is essential because of calcium's myriad intracellular and extracellular roles. The CaSR plays key roles in maintaining Ca2+oCa2+o homeostasis by detecting small changes in blood Ca2+ and modulating the production/secretion of the Ca2+-regulating hormones, PTH, CT, FGF23 and 1,25(OH)2D3, so as to appropriately regulate Ca2+ transport into or out of blood via kidney, intestine, and/or bone. When Ca2+ is high, the CaSR suppresses PTH synthesis and secretion, promotes its degradation, and inhibits parathyroid cellular proliferation. It has just the opposite effects on the C-cell, stimulating CT when Ca2+oCa2+o is high. In bone, Ca2+, acting via the CaSR, stimulates recruitment and proliferation of preosteoblasts, their differentiation to mature osteoblasts, and synthesis and mineralization of bone proteins. Conversely, Ca2+oCa2+o inhibits the formation and activity and promotes apoptosis of osteoclasts, likely via the CaSR. These actions tend to mobilize skeletal Ca2+ during Ca2+oCa2+o deficiency and retain it when Ca2+ is plentiful.