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.
Chattopadhyay
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Endocrine-Hypertension Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. nchattopadhyay@rics.bwh.harvard.edu
Brown
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EM
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D006031:Glycosylation; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics / Q000378:metabolism; D006961:Hyperparathyroidism / Q000378:metabolism; D006996:Hypocalcemia / Q000235:genetics / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D005810:Multigene Family; D010280:Parathyroid Glands / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D051381:Rats; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C473605:extracellular calcium cation-sensing receptor, rat; D010740:Phospholipases; D008274:Magnesium; D002118:Calcium