Cellular "sensing" of extracellular calcium (Ca(2+)(o)): emerging roles in regulating diverse physiological functions

The extracellular Ca(2+) (Ca(2+)(o))-sensing receptor (CaR) critically influences Ca(2+)(o) homeostasis by regulating parathyroid hormone (PTH) secretion and renal Ca(2+) handling. Moreover, its expression in intestinal and bone cells suggests roles in all of the organs involved in maintaining systemic Ca(2+)(o) homeostasis. This G-protein coupled receptor is also expressed in a wide variety of additional cells throughout the body. While our understanding of its role(s) outside of the system governing Ca(2+)(o) metabolism remains rudimentary, the CaR will probably emerge as a versatile regulator of diverse cellular functions, including proliferation, differentiation, apoptosis, gene expression and maintenance of membrane potential. Finally, the recently developed, "calcimimetic" CaR activators, exemplified by a NPS R-467 and NPS R-568, provide novel approaches to treating diseases that previously had no effective medical therapies: topic likewise covered in this review.