The calcium-sensing receptor: A molecular perspective

Endocrine Reviews

Volumn 32, Issue 1, 2011, Pages 3-30

  Magno, Aaron L ^a   Ward, Bryan K ^a   Ratajczak, Thomas ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

1 (3 METHOXYPHENYL) N (3 PHENYLPROPYL)ETHYLAMINE; 2 CHLORO 6 [3 [1,1 DIMETHYL 2 (2 NAPHTHYL)ETHYLAMINO] 2 HYDROXYPROPOXY]BENZONITRILE; AMINO ACID; BETA ARRESTIN; CALCIUM SENSING RECEPTOR; CATION; CYCLIC AMP; FILAMIN; GENTAMICIN; KANAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; NEOMYCIN; PHOSPHOLIPASE; POLYAMINE; POLYPEPTIDE; POTASSIUM CHANNEL; PROTEIN KINASE B; PROTEIN SH3; RECEPTOR ACTIVITY MODIFYING PROTEIN; RHO FACTOR; TECALCET; TOBRAMYCIN; UNCLASSIFIED DRUG;

BONE; BREAST; CENTRAL NERVOUS SYSTEM; EPIDERMIS CELL; GASTROINTESTINAL TRACT; HEART; HUMAN; IONIC STRENGTH; KIDNEY; NONHUMAN; PARATHYROID GLAND; PH; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; BONE AND BONES; CALCIUM; CALCIUM SIGNALING; CATTLE; GASTROINTESTINAL TRACT; HOMEOSTASIS; HUMANS; KIDNEY; MICE; PARATHYROID GLANDS; RATS; RECEPTORS, CALCIUM-SENSING; SIGNAL TRANSDUCTION;

EID: 79951606631     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2009-0043     Document Type: Review

References (240)

1. Ringer S 1883 A further contribution regarding the influence of the different constituents of the blood on the contraction of the heart. J Physiol 4:29-42.3
2. Carafoli E 2003 The calcium-signalling saga: tap water and protein crystals. Nat Rev Mol Cell Biol 4:326-332 (Pubitemid 36383959)
3. Brown EM, MacLeod RJ 2001 Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81:239-297 (Pubitemid 32096177)
4. Sherwood LM, Potts Jr JT, Care AD, Mayer GP, Aurbach GD 1966 Evaluation by radioimmunoassay of factors controlling secretion of parathyroid hormone. Nature 209:52-55
5. Care AD, Sherwood LM, Potts Jr JT, Aurbach GD 1966 Perfusion of isolated parathyroid gland of goat and sheep. Nature 209:55-57
6. López-Barneo J, Armstrong CM 1983 Depolarizing response of rat parathyroid cells to divalent-cations. J Gen Physiol 82:269-294 (Pubitemid 13038063)
7. Shoback D, Thatcher J, Leombruno R, Brown E 1983 Effects of extracellular Ca++ and Mg++ on cytosolic Ca++ and PTH release in dispersed bovine parathyroid cells. Endocrinology 113:424-426 (Pubitemid 13045173)
8. Kifor O, Brown EM 1988 Relationship between diacylglycerol levels and extracellular Ca-2+ in dispersed bovine parathyroid cells. Endocrinology 123:2723-2729 (Pubitemid 19012787)
9. Brown E, Enyedi P, LeBoff M, Rotberg J, Preston J, Chen C 1987 High extracellular Ca-2+ and Mg-2+ stimulate accumulation of inositol phosphates in bovine parathyroid cells. FEBS Lett 218:113-118 (Pubitemid 17090944)
10. Shoback DM, Membreno LA, McGhee JG 1988 High calcium and other divalent-cations increase inositol trisphosphate in bovine parathyroid cells. Endocrinology 123:382-389
11. Nemeth EF, Scarpa A 1987 Rapid mobilization of cellular Ca2+ in bovine parathyroid cells evoked by extracellular divalent cations. Evidence for a cell surface calcium receptor. J Biol Chem 262:5188-5196
12. Nemeth EF, Carafoli E 1990 The role of extracellular calcium in the regulation of intracellular calcium and cell-function - introduction. Cell Calcium 11:319-321 (Pubitemid 20153811)
13. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC 1993 Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature 366:575-580 (Pubitemid 24035999)
14. Garrett JE, Capuano IV, Hammerland LG, Hung BC, Brown EM, Hebert SC, Nemeth EF, Fuller F 1995 Molecular-cloning and functional expression of human parathyroid calcium receptor cDNAs. J Biol Chem 270:12919-12925
15. Chikatsu N, Fukumoto S, Takeuchi Y, Suzawa M, Obara T, Matsumoto T, Fujita T 2000 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 (Pubitemid 30159653)
16. Riccardi D, Park J, Lee WS, Gamba G, Brown EM, Hebert SC 1995 Cloning and functional expression of a rat-kidney extracellular calcium polyvalent cation-sensing receptor. Proc Natl Acad Sci USA 92:131-135
17. Butters Jr RR, Chattopadhyay N, Nielsen P, Smith CP, Mithal A, Kifor O, Bai M, Quinn S, Goldsmith P, Hurwitz S, Krapcho K, Busby J, Brown EM 1997 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 (Pubitemid 27155216)
18. Oda Y, Tu CL, Chang W, Crumrine D, Kömüves L, Mauro T, Elias PM, Bikle DD 2000 The calcium sensing receptor and its alternatively spliced form in murine epidermal differentiation. J Biol Chem 275:1183-1190 (Pubitemid 30051170)
19. Skelly BJ, Franklin RJM 2007 Mutations in genes causing human familial isolated hyperparathyroidism do not account for hyperparathyroidism in Keeshond dogs. Vet J 174:652-654 (Pubitemid 350082703)
20. Gal A, Ridge TK, Graves TK 2010 Cloning and sequencing of the calcium-sensing receptor from the feline parathyroid gland. Domest Anim Endocrinol 38:57-61
21. Diaz R, Hurwitz S, Chattopadhyay N, Pines M, Yang Y, Kifor O, Einat MS, Butters R, Hebert SC, Brown EM 1997 Cloning, expression, and tissue localization of the calcium-sensing receptor in chicken (Gallus domesticus). Am J Physiol 273:R1008-R1016
22. Cima RR, Cheng I, Klingensmith ME, Chattopadhyay N, Kifor O, Hebert SC, Brown EM, Soybel DI 1997 Identification and functional assay of an extracellular calcium-sensing receptor in Necturus gastric mucosa. Am J Physiol 273:G1051-G1060
23. Loretz CA 2008 Extracellular calcium-sensing receptors in fishes. Comp Biochem Physiol A Mol Integr Physiol 149:225-245
24. Pin JP, Galvez T, Prézeau L 2003 Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol Ther 98:325-354 (Pubitemid 36638547)
25. Quinn SJ, Bai M, Brown EM 2004 pH sensing by the calcium-sensing receptor. J Biol Chem 279:37241-37249 (Pubitemid 39195430)
26. Bai M, Quinn S, Trivedi S, Kifor O, Pearce SH, Pollak MR, Krapcho K, Hebert SC, Brown EM 1996 Expression and characterization of inactivating and activating mutations in the human Ca-0(2+)-sensing receptor. J Biol Chem 271:19537-19545 (Pubitemid 26271631)
27. Bai M, Trivedi S, Brown EM 1998 Dimerization of the extracellular calcium-sensing receptor (CaR) on the cell surface of CaR-transfected HEK 293 cells. J Biol Chem 273:23605-23610 (Pubitemid 28417555)
28. Gama L, Wilt SG, Breitwieser GE 2001 Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons. J Biol Chem 276:39053-39059
29. Pidasheva S, Grant M, Canaff L, Ercan O, Kumar U, Hendy GN 2006 Calcium-sensing receptor dimerizes in the endoplasmic reticulum: biochemical and biophysical characterization of CASR mutants retained intracellularly. Hum Mol Genet 15:2200-2209 (Pubitemid 43985511)
30. Ward DT, Brown EM, Harris HW 1998 Disulfide bonds in the extracellular calcium-polyvalent cation-sensing receptor correlate with dimer formation and its response to divalent cations in vitro. J Biol Chem 273:14476-14483 (Pubitemid 28319169)
31. Hu J, Spiegel AM 2007 Structure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators. J Cell Mol Med 11:908-922 (Pubitemid 350037042)
32. Ray K, Hauschild BC, Steinbach PJ, Goldsmith PK, Hauache O, Spiegel AM 1999 Identification of the cysteine residues in the amino-terminal extracellular domain of the human Ca2+ receptor critical for dimerization. Implications for function of monomeric Ca2+ receptor. J Biol Chem 274:27642-27650
33. Reyes-Cruz G, Hu J, Goldsmith PK, Steinbach PJ, Spiegel AM 2001 Human Ca2+ receptor extracellular domain. Analysis of function of lobe I loop deletion mutants. J Biol Chem 276:32145-32151
34. Hu J, Spiegel AM 2003 Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function. Trends Endocrinol Metab 14:282-288 (Pubitemid 36988441)
35. Huang Y, Zhou Y, Yang W, Butters R, Lee HW, Li S, Castiblanco A, Brown EM, Yang JJ 2007 Identification and dissection of Ca2+-binding sites in the extracellular domain of Ca2+-sensing receptor. J Biol Chem 282:19000-19010 (Pubitemid 47100150)
36. Silve C, Petrel C, Leroy C, Bruel H, Mallet E, Rognan D, Ruat M 2005 Delineating a Ca2+ binding pocket within the Venus flytrap module of the human calcium-sensing receptor. J Biol Chem 280:37917-37923 (Pubitemid 41642404)
37. Huang Y, Zhou Y, Castiblanco A, Yang W, Brown EM, Yang JJ 2009 Multiple Ca2+-binding sites in the extracellular domain of the Ca2+-sensing receptor corresponding to cooperative Ca2+ response. Biochemistry 48:388-398
38. Goldsmith PK, Fan GF, Ray K, Shiloach J, McPhie P, Rogers KV, Spiegel AM 1999 Expression, purification, and biochemical characterization of the amino-terminal extracellular domain of the human calcium receptor. J Biol Chem 274:11303-11309
39. Fan GF, Ray K, Zhao XM, Goldsmith PK, Spiegel AM 1998 Mutational analysis of the cysteines in the extracellular domain of the human Ca2+ receptor: effects on cell surface expression, dimerization and signal transduction. FEBS Lett 436:353-356 (Pubitemid 28482960)
40. Pace AJ, Gama L, Breitwieser GE 1999 Dimerization of the calcium-sensing receptor occurs within the extracellular domain and is eliminated by Cys→Ser mutations at Cys(101) and Cys(236). J Biol Chem 274:11629-11634
41. Zhang Z, Sun S, Quinn SJ, Brown EM, Bai M 2001 The extracellular calcium-sensing receptor dimerizes through multiple types of intermolecular interactions. J Biol Chem 276:5316-5322
42. Hu J, Hauache O, Spiegel AM 2000 Human Ca2+ receptor cysteine-rich domain. Analysis of function of mutant and chimeric receptors. J Biol Chem 275:16382-16389 (Pubitemid 30366956)
43. Ray K, Adipietro KA, Chen C, Northup JK 2007 Elucidation of the role of peptide linker in calcium-sensing receptor activation process. J Biol Chem 282:5310-5317 (Pubitemid 47103116)
44. Ray K, Clapp P, Goldsmith PK, Spiegel AM 1998 Identification of the sites of N-linked glycosylation on the human calcium receptor and assessment of their role in cell surface expression and signal transduction. J Biol Chem 273:34558-34567 (Pubitemid 29008938)
45. Fan G, Goldsmith PK, Collins R, Dunn CK, Krapcho KJ, Rogers KV, Spiegel AM 1997 N-linked glycosylation of the human Ca2+ receptor is essential for its expression at the cell surface. Endocrinology 138:1916-1922 (Pubitemid 27180807)
46. Wess J 1997 G-protein-coupled receptors: molecular mechanisms involved in receptor activation and selectivity of G-protein recognition. FASEB J 11:346-354 (Pubitemid 27193939)
47. Zhao XM, Hauache O, Goldsmith PK, Collins R, Spiegel AM 1999 A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor. FEBS Lett 448:180-184 (Pubitemid 29151656)
48. Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, Bouvier M 1996 A peptide derived from a β(2)-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem 271:16384-16392 (Pubitemid 26236264)
49. Chang W, Chen TH, Pratt S, Shoback D 2000 Amino acids in the second and third intracellular loops of the parathyroid Ca2+-sensing receptor mediate efficient coupling to phospholipase C. J Biol Chem 275:19955-19963 (Pubitemid 30441602)
50. Ray K, Ghosh SP, Northup JK 2004 The role of cysteines and charged amino acids in extracellular loops of the human Ca(2+) receptor in cell surface expression and receptor activation processes. Endocrinology 145:3892-3903 (Pubitemid 39037578)
51. Hauache OM, Hu J, Ray K, Xie R, Jacobson KA, Spiegel AM 2000 Effects of a calcimimetic compound and naturally activating mutations on the human Ca2+ receptor and on Ca2+ receptor/metabotropic glutamate chimeric receptors. Endocrinology 141:4156-4163
52. Hu J, Reyes-Cruz G, Chen W, Jacobson KA, Spiegel AM 2002 Identification of acidic residues in the extracellular loops of the seven-transmembrane domain of the human Ca2+receptor critical for response to Ca2+and a positive allosteric modulator. J Biol Chem 277:46622-46631 (Pubitemid 35417662)
53. Hu J, McLarnon SJ, Mora S, Jiang J, Thomas C, Jacobson KA, Spiegel AM 2005 A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+. J Biol Chem 280:5113-5120 (Pubitemid 40288687)
54. Miedlich SU, Gama L, Seuwen K, Wolf RM, Breitwieser GE 2004 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 (Pubitemid 38248875)
55. Petrel C, Kessler A, Dauban P, Dodd RH, Rognan D, Ruat M 2004 Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J Biol Chem 279:18990-18997 (Pubitemid 38623329)
56. Hu J, Jiang J, Costanzi S, Thomas C, Yang W, Feyen JH, Jacobson KA, Spiegel AM 2006 Amissense mutation in the seven-transmembrane domain of the human Ca2+ receptor converts a negative allosteric modulator into a positive allosteric modulator. J Biol Chem 281:21558-21565 (Pubitemid 44115492)
57. Ray K, Fan GF, Goldsmith PK, Spiegel AM 1997 The carboxyl terminus of the human calcium receptor. Requirements for cell-surface expression and signal transduction. J Biol Chem 272:31355-31361 (Pubitemid 28013270)
58. Heath 3rd H, Odelberg S, Jackson CE, Teh BT, Hayward N, Larsson C, Buist NR, Krapcho KJ, Hung BC, Capuano IV, Garrett JE, Leppert MF 1996 Clustered inactivating mutations and benign polymorphisms of the calcium receptor gene in familial benign hypocalciuric hypercalcemia suggest receptor functional domains. J Clin Endocrinol Metab 81:1312-1317 (Pubitemid 26118553)
59. Awata H, Huang C, Handlogten ME, Miller RT 2001 Interaction of the calcium-sensing receptorandfilamin, a potential scaffolding protein. J Biol Chem 276:34871-34879
60. Hjälm G, MacLeod RJ, Kifor O, Chattopadhyay N, Brown EM 2001 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
61. Bai M, Janicic N, Trivedi S, Quinn SJ, Cole DE, Brown EM, Hendy GN 1997 Markedly reduced activity of mutant calcium-sensing receptor with an inserted Alu element from a kindred with familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. J Clin Invest 99:1917-1925 (Pubitemid 27175939)
62. Chang W, Pratt S, Chen TH, Bourguignon L, Shoback D 2001 Amino acids in the cytoplasmic C terminus of the parathyroid Ca2+-sensing receptor mediate efficient cellsurface expression and phospholipase C activation. J Biol Chem 276:44129-44136
63. Gama L, Breitwieser GE 1998 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 (Pubitemid 28509982)
64. Chang W, Tu C, Cheng Z, Rodriguez L, Chen TH, Gassmann M, Bettler B, Margeta M, Jan LY, Shoback D 2007 Complex formation with the type B γ-aminobutyric acid receptor affects the expression and signal transduction of the extracellular calcium-sensing receptor. Studies with HEK-293 cells and neurons. J Biol Chem 282:25030-25040 (Pubitemid 47347560)
65. Bai M, Trivedi S, Lane CR, Yang Y, Quinn SJ, Brown EM 1998 Protein kinase C phosphorylation of threonine at position 888 in Ca-0(2+)-sensing receptor (CaR) inhibits coupling to Ca2+ store release. J Biol Chem 273:21267-21275 (Pubitemid 28385419)
66. Jiang YF, Zhang Z, Kifor O, Lane CR, Quinn SJ, Bai M 2002 Protein kinase C (PKC) phosphorylation of the Ca2+-sensing receptor (CaR) modulates functional interaction of G proteins with the CaR cytoplasmic tail. J Biol Chem 277:50543-50549 (Pubitemid 36042212)
67. Bösel J, John M, Freichel M, Blind E 2003 Signaling of the human calcium-sensing receptor expressed in HEK293-cells is modulated by protein kinases A and C. Exp Clin Endocrinol Diabetes 111:21-26 (Pubitemid 36336812)
68. Davies SL, Ozawa A, McCormick WD, Dvorak MM, Ward DT 2007 Protein kinase C-mediated phosphorylation of the calcium-sensing receptor is stimulated by receptor activation and attenuated by calyculin-sensitive phosphatase activity. J Biol Chem 282:15048-15056 (Pubitemid 47093375)
69. Riccardi D 2002 Cell surface, ion-sensing receptors. Exp Physiol 87:403-411 (Pubitemid 34814568)
70. Hammerland LG, Krapcho KJ, Garrett JE, Alasti N, Hung BC, Simin RT, Levinthal C, Nemeth EF, Fuller FH 1999 Domains determining ligand specificity for Ca2+ receptors. Mol Pharmacol 55:642-648 (Pubitemid 29165428)
71. Conigrave AD, Quinn SJ, Brown EM 2000 L-amino acid sensing by the extracellular Ca2+-sensing receptor. Proc Natl Acad Sci USA 97:4814-4819 (Pubitemid 30238640)
72. Lee HJ, Mun HC, Lewis NC, Crouch MF, Culverston EL, Mason RS, ConigraveAD2007 Allosteric activation of the extracellular Ca2+-sensing receptor by L-amino acids enhances ERK1/2 phosphorylation. Biochem J 404:141-149
73. Mun HC, Culverston EL, Franks AH, Collyer CA, Clifton-Bligh RJ, Conigrave AD 2005 A double mutation in the extracellular Ca2+-sensing receptor's Venus flytrap domain that selectively disables L-amino acid sensing. J Biol Chem 280:29067-29072 (Pubitemid 41161356)
74. Trivedi R, Mithal A, Chattopadhyay N 2008 Recent updates on the calcium-sensing receptor as a drug target. Curr Med Chem 15:178-186 (Pubitemid 351234621)
75. Nemeth EF, Steffey ME, Hammerland LG, Hung BC, Van Wagenen BC, DelMar EG, Balandrin MF 1998 Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci USA 95:4040-4045 (Pubitemid 28173250)
76. Nemeth EF, Delmar EG, Heaton WL, Miller MA, Lambert LD, Conklin RL, Gowen M, Gleason JG, Bhatnagar PK, Fox J 2001 Calcilytic compounds: Potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone. J Pharmacol Exp Ther 299:323-331 (Pubitemid 32905150)
77. Bräuner-Osborne H, Wellendorph P, Jensen AA 2007 Structure, pharmacology and therapeutic prospects of family C G-protein coupled receptors. Curr Drug Targets 8:169-184 (Pubitemid 46049458)
78. Huang Y, Breitwieser GE 2007 Rescue of calcium-sensing receptor mutants by allosteric modulators reveals a conformational checkpoint in receptor biogenesis. J Biol Chem 282:9517-9525 (Pubitemid 47104573)
79. White E, McKenna J, Cavanaugh A, Breitwieser GE 2009 Pharmacochaperone- mediated rescue of calcium-sensing receptor loss-of-function mutants. Mol Endocrinol 23:1115-1123
80. Quinn SJ, Ye CP, Diaz R, Kifor O, Bai M, Vassilev P, Brown E 1997 The Ca2+-sensing receptor: a target for polyamines. Am J Physiol 273:C1315-C1323
81. Brown EM, Katz C, Butters R, Kifor O 1991 Polyarginine, polylysine, and protamine mimic the effects of high extracellular calcium concentrations on dispersed bovine parathyroid cells. J Bone Miner Res 6:1217-1225
82. Ruat M, Snowman AM, Hester LD, Snyder SH 1996 Cloned and expressed rat Ca2+-sensing receptor. Differential cooperative responses to calcium and magnesium. J Biol Chem 271:5972-5975
83. Ye C, Ho-Pao CL, Kanazirska M, Quinn S, Rogers K, Seidman CE, Seidman JG, Brown EM, Vassilev PM 1997 Amyloid-β proteins activate Ca2+-permeable channels through calcium-sensing receptors. J Neurosci Res 47:547-554 (Pubitemid 27106551)
84. Ohsu T, Amino Y, Nagasaki H, Yamanaka T, Takeshita S, Hatanaka T, Maruyama Y, Miyamura N, Eto Y 2010 Involvement of the calcium-sensing receptor in human taste perception. J Biol Chem 285:1016-1022
85. Bystrova MF, Romanov RA, Rogachevskaja OA, Churbanov GD, Kolesnikov SS 2010 Functional expression of the extracellular-Ca2+-sensing receptor in mouse taste cells. J Cell Sci 123:972-982
86. San Gabriel A, Uneyama H, Maekawa T, Torii K 2009 The calcium-sensing receptor in taste tissue. Biochem Biophys Res Commun 378:414-418
87. Brown EM, Butters R, Katz C, Kifor O 1991 Neomycin mimics the effects of high extracellular calcium concentrations on parathyroid function in dispersed bovine parathyroid cells. Endocrinology 128:3047-3054
88. McLarnon S, Holden D, Ward D, Jones M, Elliott A, Riccardi D 2002 Aminoglycoside antibiotics induce pH-sensitive activation of the calcium-sensing receptor. Biochem Biophys Res Commun 297:71-77
89. Quinn SJ, Kifor O, Trivedi S, Diaz R, Vassilev P, Brown E 1998 Sodium and ionic strength sensing by the calcium receptor. J Biol Chem 273:19579-19586 (Pubitemid 28367012)
90. Emanuel RL, Adler GK, Kifor O, Quinn SJ, Fuller F, Krapcho K, Brown EM 1996 Calcium-sensing receptor expression and regulation by extracellular calcium in the AtT-20 pituitary cell line. Mol Endocrinol 10:555-565 (Pubitemid 26142581)
91. Kifor O, Diaz R, Butters R, Brown EM 1997 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 (Pubitemid 27200322)
92. Huang C, Hujer KM, Wu Z, Miller RT 2004 The Ca2+-sensing receptor couples to G α(12/13) to activate phospholipase D in Madin-Darby canine kidney cells. Am J Physiol Cell Physiol 286:C22-C30 (Pubitemid 38055809)
93. Handlogten ME, Huang C, Shiraishi N, Awata H, Miller RT 2001 The Ca2+-sensing receptor activates cytosolic phospholipase A2 via a Gqα-dependent ERK-independent pathway. J Biol Chem 276:13941-13948
94. Kifor O, MacLeod RJ, Diaz R, Bai M, Yamaguchi T, Yao T, Kifor I, Brown EM 2001 Regulation of MAP kinase by calcium-sensing receptor in bovine parathyroid and CaR-transfected HEK293 cells. Am J Physiol Renal Physiol 280:F291-F302
95. Ogata S, Kubota Y, Satoh S, Ito S, Takeuchi H, Ashizuka M, Shirasuna K 2006 Ca2+stimulates COX-2 expression through calcium-sensing receptor in fibroblasts. Biochem Biophys Res Commun 351:808-814 (Pubitemid 44715856)
96. McNeil SE, Hobson SA, Nipper V, Rodland KD 1998 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 (Pubitemid 28049212)
97. Hobson SA, McNeil SE, Lee F, Rodland KD 2000 Signal transduction mechanisms linking increased extracellular calcium to proliferation in ovarian surface epithelial cells. Exp Cell Res 258:1-11 (Pubitemid 30461102)
98. Hobson SA, Wright J, Lee F, McNeil SE, Bilderback T, Rodland KD 2003 Activation of the MAP kinase cascade by exogenous calcium-sensing receptor. Mol Cell Endocrinol 200:189-198 (Pubitemid 36331926)
99. MacLeod RJ, Yano S, Chattopadhyay N, Brown EM 2004 Extracellular calcium-sensing receptor transactivates the epidermal growth factor receptor by a triple-membrane-spanning signaling mechanism. Biochem Biophys Res Commun 320:455-460 (Pubitemid 38798889)
100. Yano S, Macleod RJ, Chattopadhyay N, Tfelt-Hansen J, Kifor O, Butters RR, Brown EM 2004 Calcium-sensing receptor activation stimulates parathyroid hormone-related protein secretion in prostate cancer cells: role of epidermal growth factor receptor transactivation. Bone 35:664-672 (Pubitemid 39141867)
101. Hoff AO, Cote GJ, Fritsche Jr HA, Qiu H, Schultz PN, Gagel RF 1999 Calcium-induced activation of a mutant G-protein-coupled receptor causes in vitro transformation of NIH/3T3 cells. Neoplasia 1:485-491
102. Yamaguchi T, Chattopadhyay N, Kifor O, Sanders JL, Brown EM 2000 Activation of p42/44 and p38 mitogen-activated protein kinases by extracellular calcium-sensing receptor agonists induces mitogenic responses in the mouse osteoblastic MC3T3-E1 cell line. Biochem Biophys Res Commun 279:363-368 (Pubitemid 32016723)
103. Tfelt-Hansen J, MacLeod RJ, Chattopadhyay N, Yano S, Quinn S, Ren X, Terwilliger EF, Schwarz P, Brown EM 2003 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-E337 (Pubitemid 36899706)
104. Maiti A, Hait NC, Beckman MJ 2008 Extracellular calcium-sensing receptor activation induces vitamin D-receptor levels in proximal kidney HK-2G cells by a mechanism that requires phosphorylation of p38 α MAPK. J Biol Chem 283:175-183
105. Chen CJ, Barnett JV, Congo DA, Brown EM 1989 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 (Pubitemid 19033651)
106. De Jesus Ferreira MC, Bailly C 1998 Extracellular Ca2+ decreases chloride reabsorption in rat CTAL by inhibiting cAMP pathway. Am J Physiol 275:F198-F203
107. Chang W, Pratt S, Chen TH, Nemeth E, Huang Z, Shoback D 1998 Coupling of calcium receptors to inositol phosphate and cyclic AMP generation in mammalian cells and Xenopus laevis oocytes and immunodetection of receptor protein by region-specific antipeptide antisera. J Bone Miner Res 13:570-580
108. Mamillapalli R, VanHouten J, Zawalich W, Wysolmerski J 2008 Switching of G-protein usage by the calcium-sensing receptor reverses its effect on parathyroid hormone-related protein secretion in normal versus malignant breast cells. J Biol Chem 283:24435-24447
109. Dvorak MM, Siddiqua A, Ward DT, Carter DH, Dallas SL, Nemeth EF, Riccardi D 2004 Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones. Proc Natl Acad Sci USA 101:5140-5145 (Pubitemid 38469215)
110. Ward DT, Maldonado-Pérez D, Hollins L, Riccardi D 2005 Aminoglycosides induce acute cell signaling and chronic cell death in renal cells that express the calcium-sensing receptor. J Am Soc Nephrol 16:1236-1244 (Pubitemid 41716508)
111. Peiris D, Pacheco I, Spencer C, MacLeod RJ 2007 The extracellular calcium-sensing receptor reciprocally regulates the secretion of BMP-2 and the BMP antagonist Noggin in colonic myofibroblasts. Am J Physiol Gastrointest Liver Physiol 292:G753-G766 (Pubitemid 46440383)
112. Pi M, Spurney RF, Tu Q, Hinson T, Quarles LD 2002 Calcium-sensing receptor activation of rho involves filamin and rho-guanine nucleotide exchange factor. Endocrinology 143:3830-3838 (Pubitemid 35244362)
113. Rey O, Young SH, Yuan J, Slice L, Rozengurt E 2005 Amino acid-stimulated Ca2+ oscillations produced by the Ca2+-sensing receptor are mediated by a phospholipase C/inositol 1,4,5-trisphosphate-independent pathway that requires G(12), Rho, filamin-A, and the actin cytoskeleton. J Biol Chem 280:22875-22882
114. Huang C, Miller RT 2007 The calcium-sensing receptor and its interacting proteins. J Cell Mol Med 11:923-934
115. Zhang M, Breitwieser GE 2005 High affinity interaction with filamin a protects against calcium-sensing receptor degradation. J Biol Chem 280:11140-11146 (Pubitemid 40418420)
116. Huang C, Wu Z, Hujer KM, Miller RT 2006 Silencing of filamin A gene expression inhibits Ca2+-sensing receptor signaling. FEBS Lett 580:1795-1800
117. Huang C, Sindic A, Hill CE, Hujer KM, Chan KW, Sassen M, Wu Z, Kurachi Y, Nielsen S, Romero MF, Miller RT 2007 Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function. Am J Physiol Renal Physiol 292:F1073-F1081 (Pubitemid 46393434)
118. Lourdel S, Paulais M, Cluzeaud F, Bens M, Tanemoto M, Kurachi Y, Vandewalle A, Teulon J 2002 An inward rectifier K+ channel at the basolateral membrane of the mouse distal convoluted tubule: similarities with Kir4-Kir5.1 heteromeric channels. J Physiol 538:391-404 (Pubitemid 35175369)
119. Sampson LJ, Leyland ML, Dart C 2003 Direct interaction between the actin-binding protein filamin-A and the inwardly rectifying potassium channel, Kir2.1. J Biol Chem 278:41988-41997 (Pubitemid 37310462)
120. Huang Y, Niwa J, Sobue G, Breitwieser GE 2006 Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin. J Biol Chem 281:11610-11617 (Pubitemid 43855418)
121. Herrera-Vigenor F, Hernández-García R, Valadez- Sánchez M, Vázquez-Prado J, Reyes-Cruz G 2006 AMSH regulates calcium- sensing receptor signaling through direct interactions. Biochem Biophys Res Commun 347:924-930 (Pubitemid 44118207)
122. McCullough J, Clague MJ, Urbé S 2004 AMSH is an endosome-associated ubiquitin isopeptidase. J Cell Biol 166:487-492 (Pubitemid 39097168)
123. Reyes-Ibarra AP, García-Regalado A, Ramírez-Rangel I, Esparza-Silva AL, Valadez-Sánchez M, Vázquez-Prado J, Reyes-Cruz G 2007 Calcium-sensing receptor endocytosis links extracellular calcium signaling to parathyroid hormone-related peptide secretion via a Rab11a-dependent and AMSH-sensitive mechanism. Mol Endocrinol 21:1394-1407 (Pubitemid 46984745)
124. DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK 2007 β-Arrestins and cell signaling. Annu Rev Physiol 69:483-510
125. Pi M, Oakley RH, Gesty-Palmer D, Cruickshank RD, Spurney RF, Luttrell LM, Quarles LD 2005 β-Arrestin-and G protein receptor kinase-mediated calcium-sensing receptor desensitization. Mol Endocrinol 19:1078-1087 (Pubitemid 40397070)
126. Lorenz S, Frenzel R, Paschke R, Breitwieser GE, Miedlich SU 2007 Functional desensitization of the extracellular calcium-sensing receptor is regulated via distinct mechanisms: role of G protein-coupled receptor kinases, protein kinase C and β-arrestins. Endocrinology 148:2398-2404 (Pubitemid 46997055)
127. Morfis M, Christopoulos A, Sexton PM 2003 RAMPs: 5 years on, where to now? Trends Pharmacol Sci 24:596-601
128. Bouschet T, Martin S, Henley JM 2005 Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane. J Cell Sci 118:4709-4720 (Pubitemid 41646381)
129. Brown EM 2000 The extracellular Ca2+-sensing receptor: central mediator of systemic calcium homeostasis. Annu Rev Nutr 20:507-533
130. Quarles LD 2003 Extracellular calcium-sensing receptors in the parathyroid gland, kidney, and other tissues. Curr Opin Nephrol Hypertens 12:349-355 (Pubitemid 36871857)
131. Thakker RV 2004 Diseases associated with the extracellular calcium-sensing receptor. Cell Calcium 35:275-282 (Pubitemid 38292371)
132. Pidasheva S, D'Souza-Li L, Canaff L, Cole DE, Hendy GN 2004 CASRdb: calcium-sensing receptor locus-specific database for mutations causing familial (benign) hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat 24:107-111 (Pubitemid 39006589)
133. Hendy GN, D'Souza-Li L, Yang B, Canaff L, Cole DE 2000 Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat 16:281-296
134. Ward BK, Magno AL, Blitvich BJ, Rea AJ, Stuckey BG, Walsh JP, Ratajczak T 2006 Novel mutations in the calcium-sensing receptor gene associated with biochemical and functional differences in familial hypocalciuric hypercalcaemia. Clin Endocrinol (Oxf) 64:580-587
135. Watanabe S, Fukumoto S, Chang H, Takeuchi Y, Hasegawa Y, Okazaki R, Chikatsu N, Fujita T 2002 Association between activating mutations of calcium-sensing receptor and Bartter's syndrome. Lancet 360:692-694 (Pubitemid 35232341)
136. Kifor O, McElduff A, LeBoff MS, Moore Jr FD, Butters R, Gao P, Cantor TL, Kifor I, Brown EM 2004 Activating antibodies to the calcium-sensing receptor in two patients with autoimmune hypoparathyroidism. J Clin Endocrinol Metab 89:548-556 (Pubitemid 38269856)
137. Pallais JC, Kifor O, Chen YB, Slovik D, Brown EM 2004 Brief report: Acquired hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor. N Engl J Med 351:362-369 (Pubitemid 38944405)
138. Farnebo F, Enberg U, Grimelius L, Bäckdahl M, Schalling M, Larsson C, Farnebo LO 1997 Tumor-specific decreased expression of calcium sensing receptor messenger ribonucleic acid in sporadic primary hyperparathyroidism. J Clin Endocrinol Metab 82:3481-3486 (Pubitemid 27419108)
139. Kifor O, Moore Jr FD, Wang P, Goldstein M, Vassilev P, Kifor I, Hebert SC, Brown EM 1996 Reduced immunostaining for the extracellular Ca sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab 81:1598-1606
140. Bikle DD, Ratnam A, Mauro T, Harris J, Pillai S 1996 Changes in calcium responsiveness and handling during keratinocyte differentiation . Potential role of the calcium receptor. J Clin Invest 97:1085-1093 (Pubitemid 26070588)
141. Chattopadhyay N, Legradi G, Bai M, Kifor O, Ye C, Vassilev PM, Brown EM, Lechan RM 1997 Calcium-sensing receptor in the rat hippocampus: a developmental study. Brain Res Dev Brain Res 100:13-21 (Pubitemid 27241488)
142. Cheng I, Klingensmith ME, Chattopadhyay N, Kifor O, Butters RR, Soybel DI, Brown EM 1998 Identification and localization of the extracellular calcium-sensing receptor in human breast. J Clin Endocrinol Metab 83:703-707 (Pubitemid 28496562)
143. Buchan AM, Squires PE, Ring M, Meloche RM 2001 Mechanism of action of the calcium-sensing receptor in human antral gastrin cells. Gastroenterology 120:1128-1139 (Pubitemid 32246667)
144. Komuves L, Oda Y, Tu CL, Chang WH, Ho-Pao CL, Mauro T, BikleDD2002 Epidermal expression of the fulllength extracellular calcium-sensing receptor is required for normal keratinocyte differentiation. J Cell Physiol 192:45-54
145. Rutten MJ, Bacon KD, Marlink KL, Stoney M, Meichsner CL, Lee FP, Hobson SA, Rodland KD, Sheppard BC, Trunkey DD, Deveney KE, Deveney CW 1999 Identification of a functional Ca2+-sensing receptor in normal human gastric mucous epithelial cells. Am J Physiol 277:G662-G670 (Pubitemid 29458240)
146. Tu CL, Chang W, Xie Z, Bikle DD 2008 Inactivation of the calcium sensing receptor inhibits E-cadherin-mediated cell-cell adhesion and calcium-induced differentiation in human epidermal keratinocytes. J Biol Chem 283:3519-3528
147. Kifor O, Diaz R, Butters R, Kifor I, Brown EM 1998 The calcium-sensing receptor is localized in caveolin-rich plasma membrane domains of bovine parathyroid cells. J Biol Chem 273:21708-21713 (Pubitemid 28405345)
148. Kifor O, Kifor I, Moore Jr FD, Butters Jr RR, Brown EM 2003 m-Calpain colocalizes with the calcium-sensing receptor (CaR) in caveolae in parathyroid cells and participates in degradation of the CaR. J Biol Chem 278:31167-31176 (Pubitemid 36994632)
149. Carrillo-López N, Alvarez-Hernández D, González- Suárez I, Román-García P, Valdivielso JM, Fernández-Martín JL, Cannata-Andía JB 2008 Simultaneous changes in the calcium-sensing receptor and the vitamin D receptor under the influence of calcium and calcitriol. Nephrol Dial Transplant 23:3479-3484
150. Ritter CS, Pande S, Krits I, Slatopolsky E, Brown AJ 2008 Destabilization of parathyroid hormone mRNA by extracellular Ca2+ and the calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for gene transcription. J Mol Endocrinol 40:13-21 (Pubitemid 351279505)
151. Ho C, Conner DA, Pollak MR, Ladd DJ, Kifor O, Warren HB, Brown EM, Seidman JG, Seidman CE 1995 A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Nat Genet 11:389-394
152. Mun HC, Brennan SC, Delbridge L, Wilkinson M, Brown EM, Conigrave AD 2009 Adenomatous human parathyroid cells exhibit impaired sensitivity to L-amino acids. J Clin Endocrinol Metab 94:3567-3574
153. Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN 2009 Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism. Hum Mutat 30:85-92
154. Mizobuchi M, Ritter CS, Krits I, Slatopolsky E, Sicard G, Brown AJ 2009 Calcium-sensing receptor expression is regulated by glial cells missing-2 in human parathyroid cells. J Bone Miner Res 24:1173-1179
155. Riccardi D, Hall AE, Chattopadhyay N, Xu JZ, Brown EM, Hebert SC 1998 Localization of the extracellular Ca2+ polyvalent cation-sensing protein in rat kidney. Am J Physiol 274:F611-F622
156. Ba J, Friedman PA 2004 Calcium-sensing receptor regulation of renal mineral ion transport. Cell Calcium 35:229-237 (Pubitemid 38292366)
157. Wang WH, Lu M, Hebert SC 1996 Cytochrome P-450 metabolites mediate extracellular Ca2+-induced inhibition of apical K+ channels in the TAL. Am J Physiol 271:C103-C111
158. Aslanova UF, Morimoto T, Farajov EI, Kumagai N, Nishino M, Sugawara N, Ohsaga A, Maruyama Y, Tsuchiya S, Takahashi S, Kondo Y 2006 Chloride-dependent intracellular pH regulation via extracellular calcium-sensing receptor in the medullary thick ascending limb of the mouse kidney. Tohoku J Exp Med 210:291-300 (Pubitemid 44883969)
159. Abdullah HI, Pedraza PL, McGiff JC, Ferreri NR 2008 CaR activation increases TNF production by mTAL cells via a G (i)-dependent mechanism. Am J Physiol Renal Physiol 294:F345-F354
160. de Jesus Ferreira MC, Héliès-Toussaint C, Imbert-Teboul M, Bailly C, Verbavatz JM, Bellanger AC, Chabardès D 1998 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 (Pubitemid 28272819)
161. Motoyama HI, Friedman PA 2002 Calcium-sensing receptor regulation of PTH-dependent calcium absorption by mouse cortical ascending limbs. Am J Physiol Renal Physiol 283:F399-F406
162. Bustamante M, Hasler U, Leroy V, de Seigneux S, Dimitrov M, Mordasini D, Rousselot M, Martin PY, Féraille E 2008 Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism. J Am Soc Nephrol 19:109-116
163. Procino G, Carmosino M, Tamma G, Gouraud S, Laera A, Riccardi D, Svelto M, Valenti G 2004 Extracellular calcium antagonizes forskolin-induced aquaporin 2 trafficking in collecting duct cells. Kidney Int 66:2245-2255 (Pubitemid 41115287)
164. Topala CN, Schoeber JP, Searchfield LE, Riccardi D, Hoenderop JG, Bindels RJ 2009 Activation of the Ca2+-sensing receptor stimulates the activity of the epithelial Ca2+ channel TRPV5. Cell Calcium 45:331-339
165. Kirchhoff P, Geibel JP2006 Role of calcium and other trace elements in the gastrointestinal physiology. World J Gastroenterol 12:3229-3236
166. Chattopadhyay N, Cheng I, Rogers K, Riccardi D, Hall A, Diaz R, Hebert SC, Soybel DI, Brown EM 1998 Identification and localization of extracellular Ca2+-sensing receptor in rat intestine. Am J Physiol 274:G122-G130
167. Cheng I, Kifor O, Chattopadhyay N, Butters RR, Cima RR, Hebert SC, Brown EM, Soybel DI 1997 Expression of an extracellular Ca2+-sensing receptor in rat gastrointestinal tract. Gastroenterology 112:A1139-A1139 (Abstract)
168. Justinich CJ, Mak N, Pacheco I, Mulder D, Wells RW, Blennerhassett MG, MacLeod RJ 2008 The extracellular calcium-sensing receptor (CaSR) on human esophagus and evidence of expression of the CaSR on the esophageal epithelial cell line (HET-1A).AmJ Physiol Gastrointest Liver Physiol 294:G120-G129
169. Busque SM, Kerstetter JE, Geibel JP, Insogna K 2005 Ltype amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. Am J Physiol Gastrointest Liver Physiol 289:G664-G669 (Pubitemid 41377172)
170. Dufner MM, Kirchhoff P, Remy C, Hafner P, Müller MK, Cheng SX, Tang LQ, Hebert SC, Geibel JP, Wagner CA 2005 The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands. Am J Physiol Gastrointest Liver Physiol 289:G1084-G1090 (Pubitemid 41740614)
171. Ceglia L, Harris SS, Rasmussen HM, Dawson-Hughes B 2009 Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants. Osteoporos Int 20:71-78
172. Cheng SX, Okuda M, Hall AE, Geibel JP, Hebert SC 2002 Expression of calcium-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion. Am J Physiol Gastrointest Liver Physiol 283:G240-G250 (Pubitemid 34666182)
173. Cheng SX, Geibel JP, Hebert SC 2004 Extracellular polyamines regulate fluid secretion in rat colonic crypts via the extracellular calcium-sensing receptor. Gastroenterology 126:148-158 (Pubitemid 38040732)
174. Chakrabarty S, Radjendirane V, Appelman H, Varani J 2003 Extracellular calcium and calcium sensing receptor function in human colon carcinomas. Promotion of E-cadherin expression and suppression of β-catenin/TCF activation. Cancer Res 63:67-71
175. Kállay E, Kifor O, Chattopadhyay N, Brown EM, Bischof MG, Peterlik M, Cross HS 1997 Calcium-dependent c-myc proto-oncogene expression and proliferation of CACO-2 cells: a role for a luminal extracellular calcium-sensing receptor. Biochem Biophys Res Commun 232:80-83 (Pubitemid 27211923)
176. Yamaguchi T, Chattopadhyay N, Kifor O, Butters Jr RR, Sugimoto T, Brown EM 1998 Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca-0(2+))-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells. J Bone Miner Res 13:1530-1538 (Pubitemid 28465293)
177. Colloton M, Shatzen E, Miller G, Stehman-Breen C, Wada M, Lacey D, Martin D 2005 Cinacalcet HCl attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism. Kidney Int 67:467-476 (Pubitemid 40139838)
178. Chang W, Tu C, Chen TH, Komuves L, Oda Y, Pratt SA, Miller S, Shoback D 1999 Expression and signal transduction of calcium-sensing receptors in cartilage and bone. Endocrinology 140:5883-5893 (Pubitemid 30645377)
179. Chattopadhyay N, Yano S, Tfelt-Hansen J, Rooney P, Kanuparthi D, Bandyopadhyay S, Ren X, Terwilliger E, Brown EM 2004 Mitogenic action of calcium-sensing receptor on rat calvarial osteoblasts. Endocrinology 145:3451-3462 (Pubitemid 38830018)
180. Kameda T, Mano H, Yamada Y, Takai H, Amizuka N, Kobori M, Izumi N, Kawashima H, Ozawa H, Ikeda K, Kameda A, Hakeda Y, Kumegawa M 1998 Calcium-sensing receptor inmatureosteoclasts,whichareboneresorbing cells. Biochem Biophys Res Commun 245:419-422
181. Mentaverri R, Yano S, Chattopadhyay N, Petit L, Kifor O, Kamel S, Terwilliger EF, Brazier M, Brown EM 2006 The calcium sensing receptor is directly involved in both osteoclast differentiation and apoptosis. FASEB J 20:2562-2564
182. Ahlstrom M, Pekkinen M, Riehle U, Lamberg-Allardt C 2008 Extracellular calcium regulates parathyroid hormone-related peptide expression in osteoblasts and osteoblast progenitor cells. Bone 42:483-490
183. Garner SC, Pi M, Tu Q, Quarles LD 2001 Rickets in cation-sensing receptor-deficient mice: an unexpected skeletal phenotype. Endocrinology 142:3996-4005 (Pubitemid 32802673)
184. Tu Q, Pi M, Karsenty G, Simpson L, Liu S, Quarles LD 2003 Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background. J Clin Invest 111:1029-1037 (Pubitemid 36397479)
185. Rodriguez L, Tu C, Cheng Z, Chen TH, Bikle D, Shoback D, Chang W 2005 Expression and functional assessment of an alternatively spliced extracellular Ca2+-sensing receptor in growth plate chondrocytes. Endocrinology 146:5294-5303 (Pubitemid 41653042)
186. Chang W, Tu C, Chen TH, Bikle D, Shoback D 2008 The extracellular calcium-sensing receptor (CaSR) is a critical modulator of skeletal development. Sci Signal 1:ra1
187. Dvorak MM, Chen TH, Orwoll B, Garvey C, Chang W, Bikle DD, Shoback DM 2007 Constitutive activity of the osteoblast Ca2+-sensing receptor promotes loss of cancellous bone. Endocrinology 148:3156-3163 (Pubitemid 46996999)
188. Hamdy NAT 2009 Strontium ranelate improves bone micro architecture in osteoporosis. Rheumatology 48:iv9-iv13
189. Brennan TC, Rybchyn MS, Green W, Atwa S, Conigrave AD, Mason RS 2009 Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol 157:1291-1300
190. Chattopadhyay N, Quinn SJ, Kifor O, Ye C, Brown EM 2007 The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation. Biochem Pharmacol 74:438-447 (Pubitemid 46970843)
191. Fromigué O, Haÿ E, Barbara A, Petrel C, Traiffort E, Ruat M, Marie PJ 2009 Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate. J Cell Mol Med 13:2189-2199
192. Hurtel-Lemaire AS, Mentaverri R, Caudrillier A, Cournarie F, Wattel A, Kamel S, Terwilliger EF, Brown EM, BrazierM 2009 The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. J Biol Chem 284:575-584
193. Yano S, Brown EM, Chattopadhyay N 2004 Calcium-sensing receptor in the brain. Cell Calcium 35:257-264 (Pubitemid 38292369)
194. Cheng Z, Tu C, Rodriguez L, Chen TH, Dvorak MM, Margeta M, Gassmann M, Bettler B, Shoback D, Chang W 2007 Type B γ-aminobutyric acid receptors modulate the function of the extracellular Ca2+-sensing receptor and cell differentiation in murine growth plate chondrocytes. Endocrinology 148:4984-4992 (Pubitemid 47481544)
195. Washburn DL, Anderson JW, Ferguson AV 2000 The calcium receptor modulates the hyperpolarization-activated current in subfornical organ neurons. Neuroreport 11:3231-3235
196. Washburn DL, Anderson JW, Ferguson AV 2000 A subthreshold persistent sodium current mediates bursting in rat subfornical organ neurones. J Physiol 529:359-371 (Pubitemid 32007733)
197. Ye C, Ho-Pao CL, Kanazirska M, Quinn S, Seidman CE, Seidman JG, Brown EM, Vassilev PM 1997 Deficient cation channel regulation in neurons from mice with targeted disruption of the extracellular Ca2+-sensing receptor gene. Brain Res Bull 44:75-84 (Pubitemid 27375179)
198. Vassilev PM, Ho-Pao CL, Kanazirska MP, Ye C, Hong K, Seidman CE, Seidman JG, Brown EM 1997 Ca-o-sensing receptor (CaR)-mediated activation of K+ channels is blunted in CaR gene-deficient mouse neurons. Neuroreport 8:1411-1416 (Pubitemid 27242546)
199. Conley YP, Mukherjee A, Kammerer C, DeKosky ST, Kamboh MI, Finegold DN, Ferrell RE 2009 Evidence supporting a role for the calcium-sensing receptor in Alzheimer disease. Am J Med Genet B Neuropsychiatr Genet 150B:703-709
200. Chen W, Bergsman JB, Wang X, Gilkey G, Pierpoint CR, Daniel EA, Awumey EM, Dauban P, Dodd RH, Ruat M, Smith SM 2010 Presynaptic external calcium signaling involves the calcium-sensing receptor in neocortical nerve terminals. PLoS One 5:e8563
201. Harnett MT, Chen W, Smith SM 2009 Calcium-sensing receptor: a high-affinity presynaptic target for aminoglycoside-induced weakness. Neuropharmacology 57:502-505
202. Kapoor A, Satishchandra P, Ratnapriya R, Reddy R, Kadandale J, Shankar SK, Anand A 2008 An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene. Ann Neurol 64:158-167
203. Vizard TN, O'Keeffe GW, Gutierrez H, Kos CH, Riccardi D, Davies AM 2008 Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor. Nat Neurosci 11:285-291 (Pubitemid 351311792)
204. Phillips CG, Harnett MT, Chen W, Smith SM 2008 Calcium-sensing receptor activation depresses synaptic transmission. J Neurosci 28:12062-12070
205. Chattopadhyay N, Ye CP, Yamaguchi T, Kifor O, Vassilev PM, Nishimura R, Brown EM 1998 Extracellular calcium-sensing receptor in rat oligodendrocytes: expression and potential role in regulation of cellular proliferation and an outward K+ channel. Glia 24:449-458 (Pubitemid 28494764)
206. Chattopadhyay N, Ye C, Yamaguchi T, Nakai M, Kifor O, Vassilev PM, Nishimura RN, Brown EM 1999 The extracellular calcium-sensing receptor is expressed in rat microglia and modulates an outward K+ channel. J Neurochem 72:1915-1922 (Pubitemid 29185994)
207. Bandyopadhyay S, Jeong KH, Hansen JT, Vassilev PM, Brown EM, Chattopadhyay N 2007 Calcium-sensing receptor stimulates secretion of an interferon-γ-induced monokine (CXCL10) and monocyte chemoattractant protein-3 in immortalized GnRH neurons. J Neurosci Res 85:882-895 (Pubitemid 46426088)
208. Chattopadhyay N, Evliyaoglu C, Heese O, Carroll R, Sanders J, Black P, Brown EM 2000 Regulation of secretion of PTHrP by Ca2+-sensing receptor in human astrocytes, astrocytomas, and meningiomas. Am J Physiol Cell Physiol 279:C691-C699
209. Heyeraas KJ, Haug SR, Bukoski RD, Awumey EM 2008 Identification of a Ca2+-sensing receptor in rat trigeminal ganglia, sensory axons, and tooth dental pulp. Calcif Tissue Int 82:57-65
210. Mudò G, Trovato-Salinaro A, Barresi V, Belluardo N, Condorelli DF 2009 Identification of calcium sensing receptor (CaSR) mRNA-expressing cells in normal and injured rat brain. Brain Res 1298:24-36
211. VanHouten J, Dann P, McGeoch G, Brown EM, Krapcho K, Neville M, Wysolmerski JJ 2004 The calcium-sensing receptor regulates mammary gland parathyroid hormone-related protein production and calcium transport. J Clin Invest 113:598-608 (Pubitemid 38542509)
212. Sanders JL, Chattopadhyay N, Kifor O, Yamaguchi T, Butters RR, Brown EM 2000 Extracellular calcium-sensing receptor expression and its potential role in regulating parathyroid hormone-related peptide secretion in human breast cancer cell lines. Endocrinology 141:4357-4364 (Pubitemid 32055109)
213. Ardeshirpour L, Dann P, Pollak M, Wysolmerski J, VanHouten J 2006 The calcium-sensing receptor regulates PTHrP production and calcium transport in the lactating mammary gland. Bone 38:787-793 (Pubitemid 44498587)
214. VanHouten JN, Neville MC, Wysolmerski JJ 2007 The calcium-sensing receptor regulates plasma membrane calcium adenosine triphosphatase isoform 2 activity in mammary epithelial cells: a mechanism for calcium-regulated calcium transport into milk. Endocrinology 148:5943-5954 (Pubitemid 350146194)
215. Huang C, Hydo LM, Liu S, Miller RT 2009 Activation of choline kinase by extracellular Ca2+ is Ca2+-sensing receptor, G α(12) and Rho-dependent in breast cancer cells. Cell Signal 21:1894-1900
216. El Hiani Y, Ahidouch A, Lehen'kyi V, Hague F, Gouilleux F, Mentaverri R, Kamel S, Lassoued K, Brûlé G, Ouadid-Ahidouch H 2009 Extracellular signal-regulated kinases 1 and 2 and TRPC1 channels are required for calcium-sensing receptor-stimulated MCF-7 breast cancer cell proliferation. Cell Physiol Biochem 23:335-346
217. Journé F, Dumon JC, Kheddoumi N, Fox J, Laïos I, Leclercq G, Body JJ 2004 Extracellular calcium downregulates estrogen receptor α and increases its transcriptional activity through calcium-sensing receptor in breast cancer cells. Bone 35:479-488 (Pubitemid 38953196)
218. Liu G, Hu X, Varani J, Chakrabarty S 2009 Calcium and calcium sensing receptor modulates the expression of thymidylate synthase. NAD(P)H:quinone oxidoreductase 1 and survivin inhumancolon carcinoma cells: promotion of cytotoxic response to mitomycin C and fluorouracil. Mol Carcinog 48:202-211
219. Mihai R, Stevens J, McKinney C, Ibrahim NBN 2006 Expression of the calcium receptor inhumanbreast cancer - a potential new marker predicting the risk of bone metastases. Eur J Surg Oncol 32:511-515
220. Saidak Z, Boudot C, Abdoune R, Petit L, Brazier M, Mentaverri R, Kamel S 2009 Extracellular calcium promotes the migration of breast cancer cells through the activation of the calcium sensing receptor. Exp Cell Res 315:2072-2080
221. Liao J, Schneider A, Datta NS, McCauley LK 2006 Extracellular calcium as a candidate mediator of prostate cancer skeletal metastasis. Cancer Res 66:9065-9073 (Pubitemid 44521125)
222. Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski ZM, Poznansky MC, Kos CH, Pollak MR, Brown EM, Scadden DT 2006 Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439:599-603 (Pubitemid 43185384)
223. Tommila M, Jokilammi A, Terho P, Wilson T, Penttinen R, Ekholm E 2009 Hydroxyapatite coating of cellulose sponges attracts bone-marrow-derived stem cells in rat subcutaneous tissue. J R Soc Interface 6:873-880
224. Oda Y, Tu CL, Pillai S, Bikle DD 1998 The calcium sensing receptor and its alternatively spliced form in keratinocyte differentiation. J Biol Chem 273:23344-23352 (Pubitemid 28417522)
225. Turksen K, Troy TC 2003 Overexpression of the calcium sensing receptor accelerates epidermal differentiation and permeability barrier formation in vivo. Mech Dev 120:733-744 (Pubitemid 36794454)
226. Arabzadeh A, Troy TC, Turksen K 2009 Insights into the role of the calcium sensing receptor in epidermal differentiation in vivo. Mol Biotechnol 43:264-272
227. Finney BA, del Moral PM, Wilkinson WJ, Cayzac S, Cole M, Warburton D, Kemp PJ, Riccardi D 2008 Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR. J Physiol 586:6007-6019
228. Wang R, Xu C, Zhao W, Zhang J, Cao K, Yang B, Wu L 2003 Calcium and polyamine regulated calcium-sensing receptors in cardiac tissues. Eur J Biochem 270:2680-2688 (Pubitemid 36733535)
229. Zhang WH, Fu SB, Lu FH, Wu B, Gong DM, Pan ZW, Lv YJ, Zhao YJ, Li QF, Wang R, Yang BF, Xu CQ 2006 Involvement of calcium-sensing receptor in ischemia/reperfusion-induced apoptosis in rat cardiomyocytes. Biochem Biophys Res Commun 347:872-881 (Pubitemid 44118200)
230. Tastan I, Schreckenberg R, Mufti S, Abdallah Y, Piper HM, Schlüter KD 2009 Parathyroid hormone improves contractile performance of adult rat ventricular cardiomyocytes at low concentrations in a non-acute way. Cardiovasc Res 82:77-83
231. Sun YH, Liu MN, Li H, Shi S, Zhao YJ, Wang R, Xu CQ 2006 Calcium-sensing receptor induces rat neonatal ventricular cardiomyocyte apoptosis. Biochem Biophys Res Commun 350:942-948 (Pubitemid 44584183)
232. Tfelt-Hansen J, Hansen JL, Smajilovic S, Terwilliger EF, Haunso S, Sheikh SP 2006 Calcium receptor is functionally expressed in rat neonatal ventricular cardiomyocytes. Am J Physiol Heart Circ Physiol 290:H1165-H1171
233. Wang LN, Wang C, Lin Y, Xi YH, Zhang WH, Zhao YJ, Li HZ, Tian Y, Lv YJ, Yang BF, Xu CQ 2008 Involvement of calcium-sensing receptor in cardiac hypertrophy-induced by angiotensin II through calcineurin pathway in cultured neonatal rat cardiomyocytes. Biochem Biophys Res Commun 369:584-589
234. Fanghao L, Zhiliang T, Weihua Z, Yajun Z, Shuzhi B, Huan R, He C, Xue Y, Jingxiao W, Lina W, Hong L, Zhenwei P, Ye T, Baofeng Y, Rui W, Changqing X 2009 Calcium-sensing receptors induce apoptosis in rat cardiomyocytes via the endo(sarco)plasmic reticulum pathway during hypoxia/reoxygenation. Basic Clin Pharmacol Toxicol 106:396-405
235. Jin G, Hong-zhu L, Wei-hua Z, Lu-chuan W, Li-na W, Li Z, Guang-wei L, Hong-xia L, Bao-feng Y, Lingyun W, Rui W, Chang-qing X 2010 Increased expression of calcium-sensing receptors induced by ox-LDL amplifies apoptosis of cardiomyocytes during simulated ischaemia/reperfusion. Clin Exp Pharmacol Physiol 37:e128-e135
236. Berra Romani R, Raqeeb A, Laforenza U, Scaffino MF, Moccia F, Avelino-Cruz JE, Oldani A, Coltrini D, Milesi V, Taglietti V, Tanzi F 2009 Cardiac microvascular endothelial cells express a functional Ca2+-sensing receptor. J Vasc Res 46:73-82
237. Smajilovic S, Hansen JL, Christoffersen TE, Lewin E, Sheikh SP, Terwilliger EF, Brown EM, Haunso S, Tfelt-Hansen J 2006 Extracellular calcium sensing in rat aortic vascular smooth muscle cells. Biochem Biophys Res Commun 348:1215-1223 (Pubitemid 44308418)
238. Ziegelstein RC, Xiong Y, He C, Hu Q 2006 Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells. Biochem Biophys Res Commun 342:153-163 (Pubitemid 43247372)
239. Evenepoel P 2008 Calcimimetics in chronic kidney disease: evidence, opportunities and challenges. Kidney Int 74:265-275 (Pubitemid 352001237)
240. Kumar S, Matheny CJ, Hoffman SJ, Marquis RW, Schultz M, Liang X, Vasko JA, Stroup GB, Vaden VR, Haley H, Fox J, DelMar EG, Nemeth EF, Lago AM, Callahan JF, Bhatnagar P, Huffman WF, Gowen M, Yi B, Danoff TM, Fitzpatrick LA 2010 An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation. Bone 46:534-542