Advertisement

Endocrine Pathology

, Volume 15, Issue 3, pp 187–219 | Cite as

Calcium sensing by endocrine cells

Review

Abstract

The elucidation of the structure and function of the Ca2+-sensing receptor (CaR) has provided important insights into the normal control of Cao 2+ 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 1o and 2o hyperparathyroidism, which could, contribute to the defective Ca2+ o sensing in these conditios. The recent discovery of calciumimetics, 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 1o hyperparathyroidism.

Key Words

Calcium sensing receptor parathyroid cell familial hypocalciuric hypercalcemia endocrine cells calcimimetics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Brown EM, Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messengers. Physiol Rev 71:371–411, 1991.PubMedGoogle Scholar
  2. 2.
    Bringhurst FR, Demay MB, Kronenberg HM, Hormones and disorders of mineral metabolism. In: Wilson JD, Foster DW, Kronenberg HM, et al., eds. Williams textbook of endocrinology, 9th ed, Philadelphia, PA: W.B. Saunders, 1998; 1155–1209.Google Scholar
  3. 3.
    Berridge M, Lipp M, Bootman M. Calcium signalling. Curr Biol 9:R157-R159, 1999.PubMedCrossRefGoogle Scholar
  4. 4.
    Brown EM. Physiology and pathophysiology of the extracellular calcim-sensing receptor. Am J Med 106:238–253, 1999.PubMedCrossRefGoogle Scholar
  5. 5.
    Quamme GA, Effect of hypercalcemia on renal tubular handling of calcium and magnesium. Can J Physiol Pharmacol 60:1275–1280, 1982.PubMedGoogle Scholar
  6. 6.
    Weisinger JR, Favus MJ, Langman CB, et al. Regulation of 1,25-dihydroxyvitamin D3 by calcium in the parathyroidectomized, parathyroid hormone-replete rat. J Bone Miner Res 4:929–935, 1989.PubMedCrossRefGoogle Scholar
  7. 7.
    Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81:239–297, 2001.PubMedGoogle Scholar
  8. 8.
    Brown EM, Gamba G, Riccardi D, et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 366:575–580, 1993.PubMedCrossRefGoogle Scholar
  9. 9.
    Garrett JE, Tamir H, Kifor O, et al. Calcitonin-secreting cells of the thyroid express an extracellular calcium receptor gene. Endocrinology 136:5202–5211, 1995.PubMedCrossRefGoogle Scholar
  10. 10.
    Riccardi D, Hall AE, Chattopadhyay N, et al. Localization of the extracellular Ca2+/polyvalent cation-sensing protein in rat kidney. Am J Physiol 274:F611–622, 1998.PubMedGoogle Scholar
  11. 11.
    Rasschaert J, Malaisse WJ, The G-proteincoupled, extracellular Ca(2+)-sensing receptor: expression in pancreatic islet B-cells and possible role in the regulation of insulin release. Mol Genet Metab 68:328–331, 1999.PubMedCrossRefGoogle Scholar
  12. 12.
    Garrett JE, Capuano IV, Hammerland LG, et al. Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. J Biol Chem 270:12919–12925, 1995.PubMedCrossRefGoogle Scholar
  13. 13.
    Lavender AR, Pullman TN, Changes in inogranic phosphate excretion induced by renal arterial infusion of calcium. Am J Physiol 205:1025–1032, 1963.PubMedGoogle Scholar
  14. 14.
    Hu J, Spiegel AM. Naturally occurring mutations in the extracellular Ca2+-sensing receptor: implications for its structure and function. Trends Endocrinol Metabol 14:282–288, 2003.CrossRefGoogle Scholar
  15. 15.
    Felder CB, Graul RC, Lee AY, et al. The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors. AAPS PharmSci 1:E2, 1999.PubMedCrossRefGoogle Scholar
  16. 16.
    Oh B-H, Pandit J, Kang C-H, et al. Threedimensional structures of the periplasmic lysine/arginine/ornithine-binding protein with and without a ligand. J Biol Chem 268:11348–11355, 1993.PubMedGoogle Scholar
  17. 17.
    Galvez T, Parmentier ML, Joly C, et al. Mutagenesis and modeling of the GABAB receptor extracellular domain support a venus flytrap mechanism for ligand binding. J Biol Chem 274:13362–13369, 1999.PubMedCrossRefGoogle Scholar
  18. 18.
    Jingami H, Nakanishi S, Morikawa K. Structure of the metabotropic glutamate receptors. Curr Opin Neurobiol 13:271–278, 2003.PubMedCrossRefGoogle Scholar
  19. 19.
    Ray K, Hauschild BC, Steinbach PJ, et al. Identification of the cysteine residues in the amino-terminal extracellular domain of the human Ca(2+) receptor critical for dimerization. Implications for function of monomeric Ca(2+) receptor. J Biol Chem 274:27642–27650, 1999.PubMedCrossRefGoogle Scholar
  20. 20.
    Bai M, Trivedi S, Kifor O, et al. Intermolecular interactions between dimeric calciumsensing receptor monomers are important for its normal function. Proc Natl Acad Sci USA 96:2834–2839, 1999.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang Z, Qiu, W, Quinn SJ, et al. Three adjacent serines in the extracellular domains of the CaR are required for L-amino acidmediated potentiation of receptor function. J Biol Chem 277:33727–33735, 2002.PubMedCrossRefGoogle Scholar
  22. 22.
    Jensen AA, Hansen JL, Sheikh SP, et al. Probing intermolecular protein-protein interactions in the calcium-sensing receptor homodimer using bioluminescence resonance energy transfer (BRET). Eur J Biochem 269:5076–5087, 2002.PubMedCrossRefGoogle Scholar
  23. 23.
    Fan G, Goldsmith PK, Collins R, et al. N-linked glycosylation of the human Ca2+ receptor is essential for its expression at the cell surface. Endocrinology 138:1916–1922, 1997.PubMedCrossRefGoogle Scholar
  24. 24.
    Bai M, Trivedi S, Lane CR, et al. Protein kinase C phosphorylation of threonine at position 888 in Ca2+-sensing receptor (CaR) inhibits coupling to Ca2+ store release. J. Biol Chem 273:21267–21275, 1998.PubMedCrossRefGoogle Scholar
  25. 25.
    Bosel J, John M, Freichel M, et al. Signaling of the human calcium-sensing receptor expressed in HEK293-cells in modulated by protein kinases A and C. Exp Clin Endocrinol Diabetes 111:21–26, 2003.PubMedCrossRefGoogle Scholar
  26. 26.
    Jiang YF, Zhang Z, Kifor O, et al. Protein kinase C (PKC) phosphorylation of the Ca2+ o-sensing receptor (CaR) modulates functional interaction of G proteins with the CaR cytoplasmic tail. J Biol Chem 277:50543–50549, 2002.PubMedCrossRefGoogle Scholar
  27. 27.
    Bai M, Trivedi S, Brown EM. Dimerization of the extracellular calcium-sensing receptor (CaR) on the cell surface of, CaR-transfected HEK293 cells. J Biol Chem 273:23605–23610, 1998.PubMedCrossRefGoogle Scholar
  28. 28.
    Ray K, Fan GF, Goldsmith PK, et al. The carboxyl terminus of the human calcium receptor. Requirements for cell-surface expression and signal transduction. J Biol Chem 272:31355–31361, 1997.PubMedCrossRefGoogle Scholar
  29. 29.
    Gama L, Breitwieser GE. A carboxyl-terminal domain controls the cooperativity for extracellular Ca2+ activation of the human calcium sensing receptor. A study with receptor-green fluorescent protein fusions. J Biol Chem 273:29712–29718, 1998.PubMedCrossRefGoogle Scholar
  30. 30.
    Hialm G, MacLeod RJ, Kifor O, et al. Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase. J Biol Chem 276:34880–34887, 2001.CrossRefGoogle Scholar
  31. 31.
    Awata H, Huang C, Handlogten ME, et al. Interaction of the calcium-sensing receptor and filamin, a poterntial scaffolding protein. J Biol Chem 276:34871–34879, 2001.PubMedCrossRefGoogle Scholar
  32. 32.
    Gorlin JB, Henske E, Warren ST, et al. Actibinding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28. Genomics 17:496–498, 1998.CrossRefGoogle Scholar
  33. 33.
    Stahlhut M, van Deurs B. Identification of filamin as a novel ligand for caveolin-1: evidence for the organization of caveolin-1-associated membrane domains by the actin cytoskeleton. Mol Biol Cell 11:325–337, 2000.PubMedGoogle Scholar
  34. 34.
    Marti A, Luo Z, Cunningham C, et al. Actibinding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factoralpha activation of SAPK inmelanoma cells. J Biol Chem 272:2620–2628, 1997.PubMedCrossRefGoogle Scholar
  35. 35.
    Anderson RG. The caveolae membrane system. Annu Rev Biochem 67:199–225, 1998.PubMedCrossRefGoogle Scholar
  36. 36.
    Kifor O, Diaz R, Butters R, et al. The calcium-sensing receptor is localized in caveolinrich plasma membrane domains of bovine parathyroid cells. J Biol Chem 273:21708–21713, 1998.PubMedCrossRefGoogle Scholar
  37. 37.
    Handlogten ME, Shiraishi N, Awata H, et al. Extracellular Ca(2+)-sensing receptor is a promiscuous divalent cation sensor that responds to lead. Am J Physiol Renal Physiol 279:F1083–1091, 2000.PubMedGoogle Scholar
  38. 38.
    Brown EM, Fuleihan GE-H, Chen CJ, et al. A comparison of the effects of divalent and trivalent cations on parathyroid hormone release, 3′, 5′-cyclic-adenosine monophosphate accumulatin, and the levels of inositol phosphates in bovine parathyroid cells. Endocrinology 127:1064–1071, 1990.PubMedGoogle Scholar
  39. 39.
    Quinn SJ, Kifor O, Trivedi S, et al. Sodium and ionic strength sensing by the calcium receptor. J Biol Chem 273:19579–19586, 1998.PubMedCrossRefGoogle Scholar
  40. 40.
    Quinn SJ, Ye CP, Diaz R, et al. The Ca2+-sensing receptor: a target for polyamines. Am J Physiol 273:C1315–1323, 1997.PubMedGoogle Scholar
  41. 41.
    Hammerland LG, Krapcho KJ, Alasti N, et al. Cation binding determinants of, the calcium receptor revealed by functional analysis of chimeric receptors and a deletion mutant. J Bone Miner Res 10 (suppl. 1): S156(Abstract), 1995.Google Scholar
  42. 42.
    Hammerland LG, Garrett JE, Krapcho KJ, et al. NPS R-467 activation of chimeric calcium-metabotropic glutamate receptor and a calcium receptor deletion mutant indicates a site of action within the transmembrane domain of the calcium receptor. J Bone Miner Res 11 (Suppl. 1):S158 (Abstract P272), 1996.Google Scholar
  43. 43.
    Nearing J, Betka M, Quinn S, et al. Polyvalent cation receptor proteins (CaRs) are salinity sensors in fish. Proc. Natl Acad Sci USA 99:9231–9236, 2002.PubMedCrossRefGoogle Scholar
  44. 44.
    Flanagan JA, Bendell LA, Guerreiro PM, et al. Cloning of the CDNA for the putative calcium-sensing receptor and its tissue distribution in sea bream (Sparus aurata). Gen Comp Endocrinol 127:117–127, 2002.PubMedCrossRefGoogle Scholar
  45. 45.
    McLarnon S, Holden D, Ward D, et al. Aminoglycoside antibiotics induce pH-sensing activation of the calcium-sensing receptor. Biochem Biophys Res Commun 297:71–77, 2002.PubMedCrossRefGoogle Scholar
  46. 46.
    Nemeth EF, Pharmacological regulation of parathyroid hormone secretion. Curr Pharm Des 8:2077–2087, 2002.PubMedCrossRefGoogle Scholar
  47. 47.
    Conigrave AD, Franks AH, Brown EM, et al. L-amino acid sensing by the calcium-sensing receptor: a general mechanism for coupling protein and calcium metabolism? Eur J Clin Nutr 56:1072–1080, 2002.PubMedCrossRefGoogle Scholar
  48. 48.
    McArthur KE, Isenberg JI, Hogan DL, et al. Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy. J Clin Invest 71:1254–1262, 1983.PubMedGoogle Scholar
  49. 49.
    Behar J, Hitchings M, Smyth RD. Calcium stimulation of gastrin and gastric acid secretion: effect of small doses of calcium carbonate. Gut 18:442–448, 1977.PubMedGoogle Scholar
  50. 50.
    Taylor IL, Byrne WJ, Christie DL, et al. Effect of individual-amino acids on gastric acid secretion and serum gastrin and pancreatic polypeptide release in humans. Gastroenterology 83:273–278, 1982.PubMedGoogle Scholar
  51. 51.
    Nemeth EF, Steffey ME, Hammerland LG, et al. Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci USA 95:4040–4045, 1998.PubMedCrossRefGoogle Scholar
  52. 52.
    Block GA, Martin KJ, de Francisco AL, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350:1516–1525, 2004.PubMedCrossRefGoogle Scholar
  53. 53.
    Miedlich SU, Gama L, Seuwen K, et al. Homology modeling of the transmembrane domain of the human calcium sensing receptor and localization of an allosteric binding site. J Biol Chem 279:7254–7263, 2004.PubMedCrossRefGoogle Scholar
  54. 54.
    Nemeth EF. The search for calcium receptor antagonists (calcilytics). J Mol Endocrinol 29:15–21, 2002.PubMedCrossRefGoogle Scholar
  55. 55.
    Emanuel RL, Adler GK, Kifor O, et al. Calcium-sensing receptor expression and regulation by extracellular calcium in the AtT-20 pituitary cell line. Mol Endocrinol 10:555–565, 1996.PubMedCrossRefGoogle Scholar
  56. 56.
    Yarden N, Lavelin I, Genina O, et al. Expression of calcium-sensing receptor gene by avian parathyroid gland in vivo: relationship to plasma calcium. Gen Comp Endocrinol 117:173–181, 2000.PubMedCrossRefGoogle Scholar
  57. 57.
    Suzuki K, Lavaroni S, Mori A, et al. Thyroid transcription factor 1 is calcium modulate and coordinately regulates genes involved in calcium homeostasis in C cells. Mol Cell Biol 18:7410–7422, 1998.PubMedGoogle Scholar
  58. 58.
    Mantovani G, Corbetta S, Romoli R, et al. Absence of thyroid transcription factor-1 expression in human parathyroid and pituitary glands. Mol Cell Endocrinol 182:13–17, 2001.PubMedCrossRefGoogle Scholar
  59. 59.
    Canaff L, Hendy GN. Human calcium-sensing receptorgene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. J Biol Chem 277:30337–30350, 2002.PubMedCrossRefGoogle Scholar
  60. 60.
    Garfia B, Canadillas S, Canalejo A, et al. Regulation of parathyroid vitamin D receptor expression by extracellular calcium. J Am Soc Nephrol 13:2945–2952, 2002.PubMedCrossRefGoogle Scholar
  61. 61.
    Naveh-Many T, Marx R, Keshet E, et al. Regulation of 1,25-dihydroxyvitamin D3 receptor gene expression by 1,25-dihydroxy-vitamin D3 in the parathyroid gland in vivo. J Clin Invest 86:1969–1975, 1990.Google Scholar
  62. 62.
    Clemens T, McGlade S, Garrett K, et al. Extracellular calcium modulates vitamin D-dependent calbindin-D28k gene expression in chick kidney cells. Endocrinology 124:1582–1584, 1989.PubMedGoogle Scholar
  63. 63.
    Nielsen PK, Rasmussen AK, Butters R, et al. Inhibition of PTH secretion by interleukin-1 beta in bovine parathyroid glands in vitro is associated with an up-regulation of the calcium-sensing receptor mRNA. Biochem Biophys Res Commun 238:880–885, 1997.PubMedCrossRefGoogle Scholar
  64. 64.
    Toribio RE, Kohn CW, Capen CC, et al. Parathyroid hormone (PTH) secretion, PTH mRNA and calcium-sensing receptor mRNA expression in equine parathyroid cells, and effects of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha on equine parathyroid cell function. J Mol Endocrinol 31:609–620, 2003.PubMedCrossRefGoogle Scholar
  65. 65.
    Toribio RE, Kohn CW, Sams RA, et al. Hysteresis and calcium set-point for the calcium parathyroid hormone relationship in healthy horses. Gen Comp Endocrinol 130:279–288, 2003.PubMedCrossRefGoogle Scholar
  66. 66.
    Murphey ED, Chattopadhyay N, Bai M, et al. Up-regulation of the parathyroid calcium-sensing receptor after burn injury in sheep: a potential contributory factor to postburn hypocalcemia. Crit Care Med 28:3885–3890, 2000.PubMedCrossRefGoogle Scholar
  67. 67.
    Chattopadhyay N, Baum M, Bai M, et al. Ontogeny of the extracellular calcium-sensing receptor in rat kidney. Am J Physiol 271:F736–743, 1996.PubMedGoogle Scholar
  68. 68.
    Chattopadhyay N, Legradi G, Bai M, et al. Calcium-sensing receptor in the rat hippocampus: a developmental study. Brain Res Dev Brain Res 100:13–21, 1997.PubMedCrossRefGoogle Scholar
  69. 69.
    Mithal A, Kifor O, Kifor I, et al. The reduced responsiveness of cultured bovine parathyroid cells to extracellular Ca2+ is associated with marked reduction in the expression of extracellular Ca(2+)-sensing receptor messenger ribonucleic acid and protein. Endocrinology 136:3087–3092, 1995.PubMedCrossRefGoogle Scholar
  70. 70.
    Ritter CS, Slatopolsky E, Santoro S, et al. Parathyroid cells cultured in collagen matrix retain calcium responsiveness: improtance of three-dimensional tissue architecture. J Bone Miner Res 19:491–498, 2004.PubMedCrossRefGoogle Scholar
  71. 71.
    Mathias R, Nguyen H, Zhang M, et al. Expression of the renal calcium-sensing receptor is reduced in rats with experimental chronic renal insufficiency. J Bone Miner Res 12:S326 (abstract F400), 1997.Google Scholar
  72. 72.
    Riccardi D, Traebert M, Ward DT, et al. Dietary phosphate and parathyroid hormone alter the expression of the calcium-sensing receptor (CaR) and the Na+-dependent Pi transporter (NaPi-2) in the rat proximal tubule. Pflugers Arch 441:379–387, 2000.PubMedCrossRefGoogle Scholar
  73. 73.
    Brown AJ, Ritter CS, Finch JL, et al. Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: role of dietary phosphate. Kidney Int 55:1284–1292, 1999.PubMedCrossRefGoogle Scholar
  74. 74.
    Ritter CS, Martin DR, Lu Y, et al. Reversal of secondary hyperparathyroidism by phosphate restriction restores parathyroid calcium-sensing receptor expression and fuction. J Bone Miner Res 17:2206–2213, 2002.PubMedCrossRefGoogle Scholar
  75. 75.
    Kifor O, Moore FD Jr., Wang P, et al. Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism [see comments]. J Clin Endocrinol Metab 81:1598–1606, 1996.PubMedCrossRefGoogle Scholar
  76. 76.
    Gogusev J, Duchambon P, Hory B, et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 51:328–336, 1997.PubMedCrossRefGoogle Scholar
  77. 77.
    Haven CJ, van Puijenbroek M, Karperien M, et al. Differential expression of the calcium sensing receptor and combined loss of chromosomes 1q and 11q in parathyroid carcinoma. J Pathol 202:86–94, 2004.PubMedCrossRefGoogle Scholar
  78. 78.
    Garner SC, Hinson TK, McCarty KS, et al. Quantitative analysis of the calcium-sensing receptor messenger RNA in parathyroid adenomas. Surgery 122:1166–1175, 1997.PubMedCrossRefGoogle Scholar
  79. 79.
    Tfelt-Hansen J, Schwarz P, Brown EM, et al. The calcium-sensing receptor in human disease. Front Biosci 8:s377–390, 2003.PubMedCrossRefGoogle Scholar
  80. 80.
    Simonds WF, James-Newton LA, Agarwal SK, et al. Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds. Medicine (Baltimore) 81:1–26, 2002.CrossRefGoogle Scholar
  81. 81.
    Martin-Salvago M, Villar-Rodriguez JL, Palma-Alvarez A, et al. Decreased expression of calcium receptor in parathyroid tissue in patients with hyperparathyroidism secondary to chronic renal failure. Endocr Pathol 14:61–70, 2003.PubMedCrossRefGoogle Scholar
  82. 82.
    Chikatsu N, Fukumoto S, Takeuchi Y, et al. Cloning and characterization of two promoters for the human calcium-sensing receptor (CaSR) and changes of CaSR expression in parathyroid adenomas. J Biol Chem 275: 7553–7557, 2000.PubMedCrossRefGoogle Scholar
  83. 83.
    Cetani F, Picone A, Cerrai P, et al. Parathyroid expression of calcium-sensing receptor protein and in vivo parathyroid hormone-Ca(2+) set-point in patients with pamary hyperparathyroidism. J Clin Endocrinol Metab 85:4789–4794, 2000.PubMedCrossRefGoogle Scholar
  84. 84.
    Corbetta S, Mantovani G, Lania A, et al. Calcium-sensing receptor expression and signalling in human parathyroid adenomas and primary hyperplasia. Clin Endocrinol (Oxf) 52:339–348, 2000.CrossRefGoogle Scholar
  85. 85.
    Kifor O, Diaz R, Butters R, et al. The Ca2+-sensing receptor (CaR) activates phospholipases C, A2, and D in bovine parathyroid and CaR-transfected, human embryonic kidney (HEK293) cells. J Bone Miner Res 12:715–725, 1997.PubMedCrossRefGoogle Scholar
  86. 86.
    Nemeth E, Scarpa A. Rapid mobilization of cellular Ca2+ in bovine parathyroid cells by external divalent cations. J Biol Chem 202:5188–5196, 1987.Google Scholar
  87. 87.
    Chang W, Chen TH, Gardner P, et al. Regulation of Ca(2+)-conducting currents in parathyroid cells by extracellular Ca(2+) and channel blockers. Am J Physiol 269:E864–877, 1995.PubMedGoogle Scholar
  88. 88.
    Ye C, Rogers K, Bai M, et al. Agonists of the Ca(2+)-sensing receptor (CaR) activate nonselective cation channels in HEK293 cells stably transfected with the human CaR. Biochem Biophys Res Commun 226:572–579, 1996.PubMedCrossRefGoogle Scholar
  89. 89.
    Huang C, Handlogten ME, Miller RT. Parallel activation of phosphatidylinositol 4-kinase and phospholipase C by the extracellular calcium-sensing receptor. J Biol Chem 277:20293–20300, 2002.PubMedCrossRefGoogle Scholar
  90. 90.
    Kifor O, MacLeod RJ, Diaz R, et al. Regulation of MAP kinase by calcium-sensing receptor in bovine parathyroid and CaR-transfected HEK293 cells. Am J Physiol Renal Physiol 280:F291–302, 2001.PubMedGoogle Scholar
  91. 91.
    Handlogten ME, Huang C, Shiraishi N, et al. The Ca2+-sensing receptor activates cytosolic phospholipase A2 via a Gqalpha-dependent ERK-independent pathway. J Biol Chem 276:13941–13948, 2001.PubMedGoogle Scholar
  92. 92.
    Huang C, Hujer KM, Wu Z, et al. The Ca2+-sensing receptor couples to Galpha 12/13 to activate phospholipase D in Madin-Darby canine kidney cells. Am J Physiol Cell Physiol 286:C22–30, 2004.PubMedCrossRefGoogle Scholar
  93. 93.
    McNeil SE, Hobson SA, Nipper V, et al. Functional calcium-sensing receptors in rat fibroblasts are required for activation of SRC kinase and mitogen-activated protein kinase in response to extracellular calcium. J Biol Chem 273:1114–1120, 1998.PubMedCrossRefGoogle Scholar
  94. 94.
    Holstein DM, Berg KA, Leeb-Lundberg LM, et al. Calcium-sensing receptor-mediated ERK1/2 activation requires Galphai2 coupling and dynamin-independent receptor internalization. J Biol Chem 279:10060–10069, 2004.PubMedCrossRefGoogle Scholar
  95. 95.
    Hobson SA, Wright J, Lee F, et al. Activation of the MAP kinase cascade by exogenous calcium-sensing receptor. Mol Cell Endocrinol 200:189–198, 2003.PubMedCrossRefGoogle Scholar
  96. 96.
    Tfelt-Hansen J, MacLeod RJ, Chattopadhyay N, et al. Calcium-sensing receptor stimulates PTHrP release by pathways dependent on PKC, p38 MAPK, JNK, and ERK1/2 in H-500 cells. Am J Physiol Endocrinol Metab 285:E329–337, 2003.PubMedGoogle Scholar
  97. 97.
    Chen C, Barnett J, Congo D, et al. Divalent cations suppress 3′,5′-adenosine monophosphate accumulation by stimulating a pertussis toxin-sensitive guanine nucleotide-binding protein in cultured bovine parathyroid cells. Endocrinology 124:233–239, 1989.PubMedGoogle Scholar
  98. 98.
    de Jesus Ferreira MC, Helies-Toussaint C, Imbert-Teboul M, et al. Co-expression of a Ca2+-inhibitable adenylyl cyclase and of a Ca2+-sensing receptor in the cortical thick ascending limb cell of the rat kidney. Inhibition of hormone-dependent cAMP accumulation by extracellular Ca2+. J Biol Chem 273:15192–15202, 1998.PubMedCrossRefGoogle Scholar
  99. 99.
    Ho C, Conner DA, Pollak MR, et al. A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism [see comments]. Nat Genet 11:389–394, 1995.PubMedCrossRefGoogle Scholar
  100. 100.
    Wada M, Furuya Y, Sakiyama J-i, et al. The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency. J Clin Invest 100:2977–2983, 1997.PubMedGoogle Scholar
  101. 101.
    Pollak MR, Chou YH, Marx SJ, et al. Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Effects of mutant gene dosage on phenotype. J Clin Invest 93:1108–1112, 1994.PubMedGoogle Scholar
  102. 102.
    Garrett J, Steffey M, Nemeth E. The calcium receptor agonist R-568 suppresses PTH mRNA levels in cultured bovine parathyroid cells. J Bone Miner Res 10(Suppl. 1):S387 (Abstract M539), 1995.Google Scholar
  103. 103.
    Diaz R, El-Hajj Fuleihan G, Brown EM. Regulation of parathyroid function. In: Fray J, ed. Handbook of physiology, section 7, vol. Endocrinology, vol. III. Hormonal regulation of water and electrolyte balance. New York: Oxford University Press, 1998;607–662.Google Scholar
  104. 104.
    Butters RR, Jr., Chattopadhyay N, Nielsen P, et al. Cloning and characterization of a calcium-sensing receptor from the hypercalcemic New Zealand white rabbit reveals unaltered responsiveness to extracellular calcium. J Bone Miner Res 12:568–579, 1997.PubMedCrossRefGoogle Scholar
  105. 105.
    Freichel M, Zink-Lorenz A, Holloschi A, et al. Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology 137:3842–3848, 1996.PubMedCrossRefGoogle Scholar
  106. 106.
    Fudge NJ, Kovacs CS. Physiological studies in heterozygous calcium sensing receptor (CaSR) gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo. BMC Physiol 4:5, 2004.PubMedCrossRefGoogle Scholar
  107. 107.
    McGehee DS, Aldersberg M, Liu KP, et al. Mechanism of extracellular Ca2+ receptor-stimulated hormone release from sheep thyroid parafollicular cells. J Physiol (Lond) 502:31–44, 1997.CrossRefGoogle Scholar
  108. 108.
    Harty RF, Maico DG, Brown CM, et al. Effects of calcium on cholinergic-stimulated gastrin release in the rat. Mol Cell Endocrinol 37:133–138, 1984.PubMedCrossRefGoogle Scholar
  109. 109.
    Ray JM, Squires PE, Curtis SB, et al. Expression of the calcium-sensing receptor on human antral gastrin cells in culture. J Clin Invest 99:2328–2333, 1997.PubMedGoogle Scholar
  110. 110.
    Buchan AM, Squires PE, Ring M, et al. Mechanism of action of the calcium-sensing receptor in human antral gastrin cells. Gastroenterology 120:1128–1139, 2001.PubMedCrossRefGoogle Scholar
  111. 111.
    Igarashi T, Ogata E, Maruyama K, et al. Effect of calcimimetic agent, KRN568, on gastrin secretion in healthy subjects. Endocr J 47:517–523, 2000.PubMedGoogle Scholar
  112. 112.
    Goebel SU, Peghini PL, Goldsmith PK, et al. Expression of the calcium-sensing receptor in gastrinomas. J Clin Endocrinol Metab 85:4131–4137, 2000.PubMedCrossRefGoogle Scholar
  113. 113.
    Modlin IM, Jaffe BM, Sank A, et al. The early diagnosis of gastrinoma. Ann Surg 196:512–517, 1982.PubMedCrossRefGoogle Scholar
  114. 114.
    Romanus ME, Neal JA, Dilley WG, et al. Comparison of four provocative tests for the diagnosis of gastrinoma. Ann Surg 197:608–617, 1983.PubMedCrossRefGoogle Scholar
  115. 115.
    Corbetta S, Lania A, Filopanti M, et al. Mitogen-activated protein kinase cascade in human normal and tumoral parathyroid cells. J Clin Endocrinol Metab 87:2201–2205, 2002.PubMedCrossRefGoogle Scholar
  116. 116.
    Haden ST, Brown EM, Stoll AL, et al. The effect of lithium on calcium-induced changes in adrenocorticotrophin levels. J Clin Endocrinol Metab 84:198–200, 1999.PubMedCrossRefGoogle Scholar
  117. 117.
    Ferry S, Chatel B, Dodd RH, et al. Effects of divalent cations and of a calcimimetic on adrenocorticotropic hormone release in pituitary tumor cells. Biochem Biophys Res Commun 238:866–873, 1997.PubMedCrossRefGoogle Scholar
  118. 118.
    van den Hurk MJ, Ouwens DT, Scheenen WJ, et al. Expression and characterization of the extracellular Ca(2+)-sensing receptor in melanotrope cells of Xenopus laevis. Endocrinology 144:2524–2533, 2003.PubMedCrossRefGoogle Scholar
  119. 119.
    Veldhuis JD, Borges JL, Drake CR, et al. Divergent influences of calcium ions on releasing factor-stimulated anterior pituitary hormone secretion in normal man. J Clin Endocrinol Metab 59:56–61, 1984.PubMedGoogle Scholar
  120. 120.
    Davis M, Nassberg B, Borges JL, et al. Actions of calcium ions and a calcium-influx blocker on basal and TRH- and GnRH-stimulated hormone release in patients with pituitary adenomas. J Endocrinol Invest 10:427–433, 1987.PubMedGoogle Scholar
  121. 121.
    Brunt LM, Veldhuis JD, Dilley WG, et al. Stimulation of insulin secretion by a rapid intravenous calcium infusion in patients with beta-cell neoplasms of the pancreas. J Clin Endocrinol Metab 62:210–216, 1986.PubMedGoogle Scholar
  122. 122.
    Komoto I, Kato M, Itami A, et al. Expression and function of the calcium-sensing receptor in pancreatic islets and insulinoma cells. Pancreas 26:178–184, 2003.PubMedCrossRefGoogle Scholar
  123. 123.
    Rasschaert J, Malaisse WJ. Expression of the calcium-sensing receptor in pancreatic islet B-cells. Biochem Biophys Res Commun 264:615–618, 1999.PubMedCrossRefGoogle Scholar
  124. 124.
    Kato M, Doi R, Imamura M, et al. Calcium-evoked insulin release from insulinoma cells is mediated via calcium-sensing receptor. Surgery 122:1203–1211, 1997.PubMedCrossRefGoogle Scholar
  125. 125.
    Leech CA, Habener JF. Regulation of glucagon-like peptide-1 receptor and calcium-sensing receptor signaling by L-histidine. Endocrinology 144:4851–4858, 2003.PubMedCrossRefGoogle Scholar
  126. 126.
    Squires PE, Harris TE, Persaud SJ, et al. The extracellular calcium-sensing receptor on human beta-cells negatively modulates insulin secretion. Diabetes 49:409–417, 2000.PubMedCrossRefGoogle Scholar
  127. 127.
    Roy BK, Abuid J, Wendorff H, et al. Insulin release in response to calcium in the diagnosis of insulinoma. Metabolism 28:246–252, 1979.PubMedCrossRefGoogle Scholar
  128. 128.
    De Palo C, Sicolo N, Vettor R, et al. Lack of effect of calcium infusion on blood glucose and plasma insulin levels in patients with insulinova. J Clin Endocrinol Metab 52:804–806, 1981.PubMedGoogle Scholar
  129. 129.
    Adebanjo OA, Igietseme J, Huang CL, et al. The effect of extracellularly applied divalent cations on cytosolic CA2+ in murine leydig cells evidence for a Ca2+-sensing receptor. J Physiol 513 (Pt 2):399–410, 1998.PubMedCrossRefGoogle Scholar
  130. 130.
    Meike AW, Liu XH, Stringham JD. Extraccellular calcium and luteinizing hormone effects on 22-hydroxycholesterol used for testosterone production in mouse Leydig cells. Androl 12:148–151, 1991.Google Scholar
  131. 131.
    Simpson BJ, Risbridger GP, Hedger MP, et al. The role of calcium in luteinizing hormone/human chorionic gonadotrophin stimulation of Leydig cell immunoactive inhibin secretion in vitro. Mol Cell Endocrinol 75:49–56, 1991.PubMedCrossRefGoogle Scholar
  132. 132.
    Rabbani SA, Gladu J, Liu B, et al. Regulation in vivo of the growth of Leydig cell tumors by antisense ribonucleic acid for parathyroid hormone-related peptide. Endocrinology 136:5416–5422, 1995.PubMedCrossRefGoogle Scholar
  133. 133.
    Sanders JL, Chattopadhyay N, Kifor O et al. Extracellular calcium-sensing receptor (CaR) expression and its potential role in parathyroid hormone-related peptide (PTHrP) secretion in the H-500 rat Leydig cell model of humoral hypercalcemia of malignancy. Biochem Biophys Res Commun 269:427–432, 2000.PubMedCrossRefGoogle Scholar
  134. 134.
    Tfelt-Hansen J, Schwarz P, Terwilliger EF, et al. Calcium-sensing receptor induces messenger ribonucleic acid of human securin, pituitary tumor transforming gene, in rat testicular cancer. Endocrinology 144:5188–5193, 2003.PubMedCrossRefGoogle Scholar
  135. 135.
    Tfelt-Hansen J, Chattopadhyay N, Yano S, et al. Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy. Endocrinology 145:1211–1217, 2004.PubMedCrossRefGoogle Scholar
  136. 136.
    McNeil L, Hobson S, Nipper V, et al. Functional calcium-sensing receptor expression in ovarian surface epithelial cells. Am J Obstet Gynecol 178:305–313, 1998.PubMedCrossRefGoogle Scholar
  137. 137.
    Brown EM. Familial hypocalciuric hypercal cemia and other disorders with resistance to extracellular calcium. Endocrinol Metab Clin North Am 29:503–522, 2000.PubMedCrossRefGoogle Scholar
  138. 138.
    Hauache OM. Extracellular calcium-sensing receptor: structural and functional features and association with diseases. Braz J Med Biol Res 34:577–584, 2001.PubMedCrossRefGoogle Scholar
  139. 139.
    Pollak MR, Brown EM, Chou YH, et al. Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell 75:1297–1303, 1993.PubMedCrossRefGoogle Scholar
  140. 140.
    Marx SJ, Fraser D, Rapoport A. Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes. Am J Med 78:15–22, 1995.CrossRefGoogle Scholar
  141. 141.
    Marx SJ, Attie MF, Levine MA, et al. The hypocalciuric or benign variant of familial hypercalcemia: clinical and biochemical features in fifteen kindreds. Medicine (Baltimore) 60:397–412, 1981.CrossRefGoogle Scholar
  142. 142.
    Marx S, Spiegel A, Brown E, et al. Divalent cation metabolism. Familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism. Am J Med 65:235–242, 1978.PubMedCrossRefGoogle Scholar
  143. 143.
    Heath DA. Familial hypocalciuric hypercalcemia. In: Bilezikian JP, Marcus R, Levine MA, eds. The parathyroids. New York, NY: Raven Press, 1994; 699–710.Google Scholar
  144. 144.
    Heath Hd, Jackson CE, Otterud B, et al. Genetic linkage analysis in familial benign (hypocalciuric) hypercalcemia: evidence for locus heterogeneity. Am J Hum Genet 53:193–200, 1993.PubMedGoogle Scholar
  145. 145.
    Lloyd SE, Pannett AA, Dixon PH, et al. Localization of familial benign hypercalcemia, Oklahoma variant (FBHOk), to chromosome 19q13. Am J Hum Genet 64:189–195, 1999.PubMedCrossRefGoogle Scholar
  146. 146.
    Bai M, Quinn S, Trivedi S, et al. Expression and characterization of inactivating and activating mutations in the human Ca2+-sensing receptor. J Biol Chem 271:19537–19545, 1996.PubMedCrossRefGoogle Scholar
  147. 147.
    Bai M, Brown EM, Harris HW. Role of the Ca(2+)-sensing receptor in divalent mineral ion homeostasis. J Exp Biol 200:295–302, 1997.Google Scholar
  148. 148.
    Bai M, Pearce SH, Kifor O, et al. In vivo and in vitro characterization of neonatal hyperparathyroidism resulting from a denovo, heterozygous mutation in the Ca2+-sensing receptor gene: normal maternal calcium homeostasis as a cause of secondary hyperparathyroidism in familial benign hypocalciuric hypercalcemia. J Clin Invest 99:88–96, 1997.PubMedGoogle Scholar
  149. 149.
    Carling T, Szabo E, Bai M, et al. Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor [see comments]. J Clin Endocrinol Metab 85:2042–2047, 2000.PubMedCrossRefGoogle Scholar
  150. 150.
    Fukumoto S, Chikatsu N, Okazaki R, et al. Parathyroid lipohyperplasia is caused by mutations in calcium-sensing receptor (CaSR). Bone 23:S283 (abstract T346), 1998.CrossRefGoogle Scholar
  151. 151.
    Kobayashi M, Tanaka H, Tsuzuki K, et al. Two novel missense mutations in calciumsensing receptor gene associated with neonatal severe hyperparathyroidism. J Clin Endocrinol Metab 82:2716–2719, 1997.PubMedCrossRefGoogle Scholar
  152. 152.
    Aida K, Koishi S, Inoue M, et al. Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene. J Clin Endocrinol Metab 80:2594–2598, 1995.PubMedCrossRefGoogle Scholar
  153. 153.
    Pearce S, Steinmann B. Casting new light on the clinical spectrum of neonatal severe hyperparathyroidism. Clin Endocrinol (Oxf) 50:691–693, 1999.CrossRefGoogle Scholar
  154. 154.
    Pearce SH, Williamson C, Kifor O, et al. A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor [see comments]. N Engl J Med 335:1115–1122, 1996.PubMedCrossRefGoogle Scholar
  155. 155.
    Strewler GJ. Familial benign hypocalciuric hypercalcemia—from the clinic to the calcium sensor [editorial; comment]. West J Med 160:579–580, 1994.PubMedGoogle Scholar
  156. 156.
    Baron J, Winer KK, Yanovski JA, et al. Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism. Hum Mol Genet 5: 601–606, 1996.PubMedCrossRefGoogle Scholar
  157. 157.
    Watanabe T, Bai M, Lane CR, et al. Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor J Clin Endocrinol Metab 83:2497–2502, 1998.PubMedCrossRefGoogle Scholar
  158. 158.
    Sato K, Hasegawa Y, Nakae J, et al. Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene. J Clin Endocrinol Metab 87:3068–3073, 2002.PubMedCrossRefGoogle Scholar
  159. 159.
    Watanabe S, Fukumoto S, Chang H, et al. Association between activating mutations of calcium-sensing receptor and Bartter’s syndrome. Lancet 360:692–694, 2002.PubMedCrossRefGoogle Scholar
  160. 160.
    Vargas-Poussou R, Huang C, Hulin P, et al. Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome. J Am Soc Nephrol 13:2259–2266, 2002.PubMedCrossRefGoogle Scholar
  161. 161.
    Blizzard RM, Chee D, Davis W. The incidence of adrenal and other antibodies in the sera of patients with idiopathic adrenal insufficiency (Addison’s disease). Clin Exp Immunol 2:19–30, 1967.PubMedGoogle Scholar
  162. 162.
    Li Y, Song YH, Rais N, et al. Autoantibodies to the extracellular domain of the calcium sensing receptor in patients with acquired hypoparathyroidism. J Clin Invest 97:910–914, 1996.PubMedGoogle Scholar
  163. 163.
    Kifor O, McElduff A, LeBoff MS, et al. Activating antibodies to the calcium-sensing receptor in two patients with autoimmune hypoparathyroidism. J Clin Endocrinol Metab 89:548–556, 2004.PubMedCrossRefGoogle Scholar
  164. 164.
    Goswami R, Brown EM, Kochupillai N, et al. Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism. Eur J Endocrinol 150:9–18, 2004.PubMedCrossRefGoogle Scholar
  165. 165.
    Soderbergh A, Myhre AG, Ekwall O, et al. Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 89:557–562, 2004.PubMedCrossRefGoogle Scholar
  166. 166.
    Kifor O, Moore FD, Jr., Delaney M, et al. A syndrome of hypocalciuric hypercalcemia caused by autoantibodies directed at the calcium-sensing receptor. J Clin Endocrinol Metab 88:60–72, 2003.PubMedCrossRefGoogle Scholar
  167. 167.
    Garner SC, Pi M, Tu Q, et al. Rickets in cation-sensing receptor-deficient mice: an unexpected skeletal phenotype. Endocrinology 142:3996–4005, 2001.PubMedCrossRefGoogle Scholar
  168. 168.
    Kos CH, Karaplis AC, Peng JB, et al. The calcium-sensing receptor is required for normal calcium homeostasis independent of parathyroid hormone. J Clin Invest 111: 1021–1028, 2003.PubMedCrossRefGoogle Scholar
  169. 169.
    Tu Q, Pi M, Karsenty G, et al. Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background. J Clin Invest 111:1029–1037, 2003.PubMedCrossRefGoogle Scholar
  170. 170.
    Brown EM. Four parameter model of the sigmoidal relationship between parathyroid hormone release and extracellular calcium concentration in normal and abnormal parathyroid tissue. J Clin Endocrinol Metab 56:572–581, 1983.PubMedCrossRefGoogle Scholar
  171. 171.
    Gowen M, Stroup GB, Dodds RA, et al Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest 105:1595–1604, 2000.PubMedCrossRefGoogle Scholar
  172. 172.
    Silverberg SJ, Bone III HG, Marriott TB, et al. Short-term inhibition of parathyroid hormone secretion by a calcium-receptor agonist in patients with primary hyperparathyroidism. N Engl J Med 337:1506–1510, 1997.PubMedCrossRefGoogle Scholar
  173. 173.
    Collins MT, Skarulis MC, Bilezikian JP, et al. Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent [see comments]. J Clin Endocrinol Metab 83:1083–1088, 1998.PubMedCrossRefGoogle Scholar
  174. 174.
    Shoback DM, Bilezikian JP, Turner SA, et al. The calcimimetic cinacalcet normalizes serum calcium in subjects with primary hyperparathyroidism. J Clin Endocrinol Metab 88:5644–5649, 2003.PubMedCrossRefGoogle Scholar
  175. 175.
    Ogata H, Ritz E, Odoni G, et al. Beneficial effects of calcimimetics on progression of renal failure and cardiovascular risk factors. J Am Soc Nephrol 14:959–967, 2003.PubMedCrossRefGoogle Scholar
  176. 176.
    Roussanne MC, Lieberherr M, Souberbielle JC, et al. Human parathyroid cell proliferation in response to calcium, NPS R-467, calcitriol and phosphate. Eur J Clin Invest 31:610–616, 2001.PubMedCrossRefGoogle Scholar
  177. 177.
    Wada M, Ishii H, Furuya Y, et al. NPS R-568 halts or reverses osteitis fibrosa in uremic rats [see comments]. Kidney Int 53:448–453, 1998.PubMedCrossRefGoogle Scholar
  178. 178.
    Wada M, Nagano N, Furuya Y, et al. Calcimimetic NPSR-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. Kidney Int 57:50–58, 2000.PubMedCrossRefGoogle Scholar
  179. 179.
    Fox J, Lowe SH, Petty BA, et al. NPS R-568: a type II calcimimetic compound that acts on parathyroid cell calcium receptor of rats to reduce plasma levels of parathyroid hormone and calcium. J Pharmacol Exp Ther 290:473–479, 1999.PubMedGoogle Scholar
  180. 180.
    Silver J, Moallem E, Kilav R, et al. New insights into the regulation of parathyroid hormone synthesis and secretion in chronic renal failure. Nephrol Dial Transplant 11:2–5, 1996.PubMedGoogle Scholar
  181. 181.
    Sudhaker Rao D, Han ZH, Phillips ER, et al. Reduced vitamin D receptor expression in parathyroid adenomas: implications for pathogenesis. Clin Endocrinol (Oxf) 53:373–381, 2000.CrossRefGoogle Scholar
  182. 182.
    Yano S, Sugimoto T, Tsukamoto T, et al. Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism. Kidney Int 58:1980–1986, 2000.PubMedCrossRefGoogle Scholar
  183. 183.
    Antonsen JE, Sherrard DJ, Andress DL. A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure. Rapid communication. Kidney Int 53:223–227, 1998.PubMedCrossRefGoogle Scholar
  184. 184.
    Goodman WG, Frazao JM, Goodkin DA, et al. A calcimimetic agents lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism. Kidney Int 58:436–445, 2000.PubMedCrossRefGoogle Scholar
  185. 185.
    Goodman WG, Hladik GA, Turner SA, et al. The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol 13:1017–1024, 2002.PubMedGoogle Scholar
  186. 186.
    Lindberg JS, Moe SM, Goodman WG, et al. The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Kidney Int 63:248–254, 2003.PubMedCrossRefGoogle Scholar
  187. 187.
    Ohashi N, Uematsu T, Nagashima S, et al. The calcimimetic agent KRN 1493 lowers plasma parathyroid hormone and ionized calcium concentrations in patients with chronic renal failure on haemodialysis both on the day of haemodialysis and on the day without haemodialysis. Br J Clin Pharmacol 57:726–734, 2004.PubMedCrossRefGoogle Scholar
  188. 188.
    Diaz R, Hurwitz S, Chattopadhyay N, et al. Cloning, expression, and tissue localization of the calcium-sensing receptor in chicken (Gallus domesticus). Am J Physiol 273:R1008–1016, 1997.PubMedGoogle Scholar
  189. 189.
    Cima RR, Cheng I, Klingensmith ME, et al. Identification and functional assay of an extracellular calcium-sensing receptor in Necturus gastric mucosa. Am J Physiol 273:G1051–1060, 1997.PubMedGoogle Scholar
  190. 190.
    Fellner SK, Parker L. A Ca(2+)-sensing receptor modulates shark rectal gland function. J Exp Biol 205:1889–1897, 2002.PubMedGoogle Scholar
  191. 191.
    Wise A, Green A, Main MJ, et al. Calcium sensing properties of the GABA(B) receptor. Neuropharmacology 38:1647–1656, 1999.PubMedCrossRefGoogle Scholar
  192. 192.
    Raya A, Kawakami Y, Rodriguez-Esteban C, et al. Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determinator. Nature 427:121–128, 2004.PubMedCrossRefGoogle Scholar
  193. 193.
    Quist AP, Khee SK, Lin H, et al. Physiological role of gap-junctional hemichannels. Extracellular calcium-dependent isosmotic volume regulation. J Cell Biol 148:1063–1074, 2000.PubMedCrossRefGoogle Scholar
  194. 194.
    Yabini E, Paukert M, Geisler HS, et al. Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1). J Biol Chem 277:41597–41603, 2002.CrossRefGoogle Scholar
  195. 195.
    Xiong Z, Lu W, MacDonald JF. Extracellular calcium sensed by a novel cation channel in hippocampal neurons. Proc Natl Acad Sci USA 94:7012–7017 1997.PubMedCrossRefGoogle Scholar
  196. 196.
    Johnson JP, Jr, Balser JR, Bennett PB. A novel extracellular calcium sensing mechanism in voltage-gated potassium ion channels. J Neurosci 21:4143–4153, 2001.PubMedGoogle Scholar
  197. 197.
    Regelmann AG, Lesley JA, Mott C, et al. Mutational analysis of the Escherichia coli PhoQ sensor kinase: differences with the Salmonella enterica serovar Typhimurium PhoQ protein and in the mechanism of Mg2+ and Ca2+ sensing. J Bacteriol 184:5468–5478, 2002.PubMedCrossRefGoogle Scholar
  198. 198.
    Klauke N, Blanchard M, Plattner H. Polyamine triggering of exocytosis in paramecium involves an extracellular Ca(2+)/(polyvalent cation)-sensing receptor, subplasmalemmal Ca-store mobilization and store-operated Ca(2+)-influx via unspecific cation channels. J Membr Biol 174:141–156, 2000.PubMedCrossRefGoogle Scholar
  199. 199.
    Kellermayer R, Aiello DP, Miseta A, et al. Extracellular Ca(2+) sensing contributes to excess Ca(2+) accumulation and vacuolar fragmentation in a pmr1 Delta mutant of S. cerevisiae. J Cell Sci 116:1637–1646, 2003.PubMedCrossRefGoogle Scholar
  200. 200.
    Han S, Tang R, Anderson LK, et al. A cell surface receptor mediates extracellular Ca(2+) sensing in guard cells. Nature 425:196–200, 2003.PubMedCrossRefGoogle Scholar
  201. 201.
    Goetzl EJ, Graeler M, Huang MC, et al. Lysophospholipid growth factors and their G protein-coupled receptors in immunity, coronary artery disease, and cancer. Scientific World J 2:324–338, 2002.Google Scholar
  202. 202.
    He W, Miao FJ, Lin DC, et al. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature 429:188–193, 2004.PubMedCrossRefGoogle Scholar
  203. 203.
    Nelson G, Chandrashekar J, Hoon MA, et al. An amino-acid taste receptor. Nature 416:199–202, 2002.PubMedCrossRefGoogle Scholar
  204. 204.
    Chaudhari N, Landin AM, Roper SD. A metabotropic glutamate receptor variant functions as a taste receptor. Nat Neurosci 3:113–119, 2000.PubMedCrossRefGoogle Scholar
  205. 205.
    Karpe F, Frayn KN. The nicotinic acid receptor—a new mechanism for an old drug. Lancet 363:1892–1894, 2004.PubMedCrossRefGoogle Scholar
  206. 206.
    Nemeth EF, Bennett SA. Tricking the parathyroid gland with novel calcimimetic agents [editorial]. Nephrol Dial Transplant 13:1923–1925, 1998.PubMedCrossRefGoogle Scholar
  207. 207.
    Quinn SJ, Bai M, Brown EM. pH sensing by the calcium-sensing receptor. J Biol Chem 279:37241–37249, 2004.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  1. 1.Division of Endocrinology, Diabetes and HypertensionBrighamrand Women’s HospitalBoston

Personalised recommendations