The calcium-sensing receptor: Physiology, pathophysiology and car-based therapeutics: Physiology and pathophysiology of CaR

Subcellular Biochemistry

Volumn 45, Issue , 2007, Pages 139-167

  Brown, Edward M ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Acquired hypoparathyroidism; Autosomal dominant hypoparathyroidism; Calcilytic; Calcimimetic; Calcium homeostasis; Calcium sensing receptor; Familial hypocalciuric hypercalcemia; Hyperparathyroidism; Osteoporosis; Seven transmembrane receptor

Indexed keywords

CALCIUM; CALCIUM SENSING RECEPTOR;

AMINO ACID SEQUENCE; AUTOIMMUNE DISEASE; DRUG ANTAGONISM; DRUG POTENTIATION; GENETICS; HUMAN; HYPERCALCEMIA; HYPOPARATHYROIDISM; IMMUNOLOGY; INFANT; MOLECULAR GENETICS; NEWBORN; PARATHYROID GLAND; PATHOPHYSIOLOGY; PHYSIOLOGY; PRIMARY HYPERPARATHYROIDISM; REVIEW;

AMINO ACID SEQUENCE; AUTOIMMUNE DISEASES; CALCIUM; HUMANS; HYPERCALCEMIA; HYPERPARATHYROIDISM, PRIMARY; HYPOPARATHYROIDISM; INFANT; INFANT, NEWBORN; MOLECULAR SEQUENCE DATA; PARATHYROID GLANDS; RECEPTORS, CALCIUM-SENSING;

EID: 38849145209     PISSN: 03060225     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-4020-6191-2_6     Document Type: Article

References (136)

1. Aida, K, Koishi, S, Inoue, M, Nakazato, M, Tawata, M and Onaya, T, 1995, Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene, J Clin Endocrinol Metab 80: 2594-2598
2. Antonsen, JE, Sherrard, DJ and Andress, DL, 1998, A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure. Rapid communication, Kidney Int 53: 223-227
3. Attie, MF, Gill Jr, J, Stock, JL, Spiegel, AM, Downs Jr, RW, Levine, MA and Marx, SJ, 1983, Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism, J Clin Invest 72: 667-676
4. Auwerx, J, Demedts, M and Bouillon, R, 1984, Altered parathyroid set point to calcium in familial hypocalciuric hypercalcaemia, Acta Endocrinologica (Copenh) 106: 215-218
5. Awata, H, Huang, C, Handlogten, ME and Miller, RT, 2001, Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein, J Biol Chem 276: 34871-34879
6. Ba, J, Brown, D and Friedman, PA, 2003, Calcium-sensing receptor regulation of PTH-inhibitable proximal tubule phosphate transport, Am J Physiol Renal Physiol 285: F1233-1243
7. 2+-sensing receptor gene: normal maternal calcium homeostasis as a cause of secondary hyperparathyroidism in familial benign hypocalciuric hypercalcemia, J Clin Invest 99: 88-96
8. 2+osensing receptor, J Biol Chem 271: 19537-19545
9. Bai, M, Trivedi, S and Brown, EM, 1998a, Dimerization of the extracellular calcium-sensing receptor (CaR) on the cell surface of CaR-transfected HEK293 cells, J Biol Chem 273: 23605-23610
10. 2+ store release, J Biol Chem 273: 21267-21275
11. Bajwa, A, Horst, RL and Beckman, MJ, 2005, Gene profiling the effects of calcium deficiency versus 1,25-dihydroxyvitamin D induced hypercalcemia in rat kidney cortex, Arch Biochem Biophys 438: 182-194
12. Baron, J, Winer, KK, Yanovski, JA, Cunningham, AW, Laue, L, Zimmerman, D and Cutler, GB, Jr., 1996, Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism, Hum Mol Genet 5: 601-606
13. Blizzard, RM, Chee, D and Davis, W, 1966, The incidence of parathyroid and other antibodies in the sera of patients with idiopathic hypoparathyroidism, Clin Exp Immunol 1: 119-128
14. Block, GA, Martin, KJ, de Francisco, AL, Turner, SA, Avram, MM, Suranyi, MG, Hercz, G, Cunningham, J, Abu-Alfa, AK, Messa, P, Coyne, DW, Locatelli, F, Cohen, RM, Evenepoel, P, Moe, SM, Fournier, A, Braun, J, McCary, LC, Zani, VJ, Olson, KA, Drueke, TB and Goodman, WG, 2004, Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis, N Engl J Med 350: 1516-1525
15. Bringhurst, FR, Demay, MB and Kronenberg, HM. Hormones and disorders of mineral metabolism. In: Williams Textbook of Endocrinology (9th ed.), edited by Wilson JD, et alFoster DW, et alKronenberg HM, et al. Philadelphia: W.B. Saunders, 1998, p. 1155-1209
16. Brown, AJ, Zhong, M, Finch, J, Ritter, C, McCracken, R, Morrissey, J and Slatopolsky, E, 1996, Rat calcium-sensing receptor is regulated by vitamin D but not by calcium, Am J Physiol 270: F454-460
17. Brown, AJ, Zhong, M, Ritter, C, Brown, EM and Slatopolsky, E, 1995, Loss of calcium responsiveness in cultured bovine parathyroid cells is associated with decreased calcium receptor expression, Biochem Biophys Res Commun 212: 861-867
18. 2+ and other ions as extracellular (first) messengers, Physiol Rev 71: 371-411
19. Brown, EM, 2000, Familial hypocalciuric hypercalcemia and other disorders with resistance to extracellular calcium, Endocrinol Metab Clin North Am 29: 503-522
20. Brown, EM, Bai, M and Pollak, MR. Familial benign hypocalciuric hypercalcemia and other syndromes of altered responsiveness to extracellular calcium. In: Metabolic Bone Diseases and Clinically Related Disorders. (third edition ed.), edited by Krane S and Avioli LV. San Diego, CA: Academic Press, 1997, p. 479-499
21. Brown, EM, Fuleihan, Ge-H, Chen, CJ and Kifor, O, 1990, A comparison of the effects of divalent and trivalent cations on parathyroid hormone release, 3′,5′-cyclic-adenosine monophosphate accumulation, and the levels of inositol phosphates in bovine parathyroid cells, Endocrinology 127: 1064-1071
22. Brown, EM, Gamba, G, Riccardi, D, Lombardi, M, Butters, R, Kifor, O, Sun, A, Hediger, MA, Lytton, J and Hebert, SC, 1993, Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid, Nature 366: 575-580
23. Brown, EM and MacLeod, RJ, 2001, Extracellular calcium sensing and extracellular calcium signaling, Physiol Rev 81: 239-297
24. Burski, K, Torjussen, B, Paulsen, AQ, Boman, H and Bollerslev, J, 2002, Parathyroid adenoma in a subject with familial hypocalciuric hypercalcemia: coincidence or causality?, J Clin Endocrinol Metab 87: 1015-1016
25. Butters, RR, Jr., Chattopadhyay, N, Nielsen, P, Smith, CP, Mithal, A, Kifor, O, Bai, M, Quinn, S, Goldsmith, P, Hurwitz, S, Krapcho, K, Busby, J and 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
26. Canaff, L and Hendy, GN, 2002, Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D, J Biol Chem 277: 30337-30350
27. Caride, AJ, Chini, EN, Homma, S, Dousa, TP and Penniston, JT, 1998, mRNAs coding for the calciumsensing receptor along the rat nephron: effect of a low-phosphate diet, Kidney Blood Press Res 21: 305-309
28. Carling, T, Szabo, E, Bai, M, Ridefelt, P, Westin, G, Gustavsson, P, Trivedi, S, Hellman, P, Brown, EM, Dahl, N and Rastad, J, 2000, Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor, J Clin Endocrinol Metab 85: 2042-2047
29. Chang, W, Tu, C, Chen, T-H, Komuves, L, Oda, Y, Pratt, S, Miller, S and Shoback, D, 1999, Expression and signal transduction of calcium-sensing receptors in cartilage and bone, Endocrinology 140: 5883-5893
30. Chattopadhyay, N, Yano, S, Tfelt-Hansen, J, Rooney, P, Kanuparthi, D, Bandyopadhyay, S, Ren, X, Terwilliger, E and Brown, EM, 2004, Mitogenic action of calcium-sensing receptor on rat calvarial osteoblasts, Endocrinology 145: 3451-3462
31. Chou, YH, Brown, EM, Levi, T, Crowe, G, Atkinson, AB, Arnqvist, HJ, Toss, G, Fuleihan, GE, Seidman, JG and Seidman, CE, 1992, The gene responsible for familial hypocalciuric hypercalcemia maps to chromosome 3q in four unrelated families, Nat Genet 1: 295-300
32. Cole, DE, Janicic, N, Salisbury, SR and Hendy, GN, 1997, Neonatal severe hyperparathyroidism, secondary hyperparathyroidism, and familial hypocalciuric hypercalcemia: multiple different phenotypes associated with an inactivating Alu insertion mutation of the calcium- sensing receptor gene [published erratum appears in Am J Med Genet 1997 Oct 17;72(2):251-2], Am J Med Genet 71: 202-210
33. 2+- sensing receptor, Proc Natl Acad Sci U S A 97: 4814-4819
34. D'Souza-Li, L, Canaff, L, Janicic, N, Cole, DEC and Hendy, GN, 1998, An acceptor splice site mutation in the calcium-sensing receptor gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, Submitted
35. D'Souza-Li, L, Yang, B, Canaff, L, Bai, M, Hanley, DA, Bastepe, M, Salisbury, SR, Brown, EM, Cole, DE and Hendy, GN, 2002, Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia, J Clin Endocrinol Metab 87: 1309-1318
36. Eftekhari, F and Yousefzadeh, D, 1982, Primary infantile hyperparathyroidism: clinical, laboratory, and radiographic features in 21 cases, Skeletal Radiol 8: 201-208
37. Finegold, DN, Armitage, MM, Galiani, M, Matise, TC, Pandian, MR, Perry, YM, Deka, R and Ferrell, RE, 1994, Preliminary localization of a gene for autosomal dominant hypoparathyroidism to chromosome 3q13, Pediatr Res 36: 414-417
38. Foley Jr, T, Harrison, H, Arnaud, C and Harrison, H, 1972, Familial benign hypercalcemia, J Pediatr 81: 1060-1067
39. Fox, J, Lowe, SH, Petty, BA and Nemeth, EF, 1999, 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
40. Fudge, NJ and Kovacs, CS, 2004, Physiological studies in heterozygous calcium sensing receptor (CaSR) gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo, BMC Physiol 4: 5
41. Fukumoto, S, Chikatsu, N, Okazaki, R, Takeuchi, Y, Tamura, Y, Murakami, T, Obara, T and Fujita, T, 2001, Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia, Diagn Mol Pathol 10: 242-247
42. Fuleihan Gel, H, 2002, Familial benign hypocalciuric hypercalcemia, J Bone Miner Res 17 Suppl 2: N51-56
43. Garrett, JE, Capuano, IV, Hammerland, LG, Hung, BC, Brown, EM, Hebert, SC, Nemeth, EF and Fuller, F, 1995, Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs, J Biol Chem 270: 12919-12925
44. Goodman, WG, Hladik, GA, Turner, SA, Blaisdell, PW, Goodkin, DA, Liu, W, Barri, YM, Cohen, RM and Coburn, JW, 2002, The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism, J Am Soc Nephrol 13: 1017-1024
45. Goswami, R, Brown, EM, Kochupillai, N, Gupta, N, Rani, R, Kifor, O and Chattopadhyay, N, 2004, Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism, Eur J Endocrinol 150: 9-18
46. Gowen, M, Stroup, GB, Dodds, RA, James, IE, Votta, BJ, Smith, BR, Bhatnagar, PK, Lago, AM, Callahan, JF, DelMar, EG, Miller, MA, Nemeth, EF and Fox, J, 2000, Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats, J Clin Invest 105: 1595-1604
47. Grantmyre, E, 1973, Roentgenographic features of "primary" hyperparathyroidism in infancy, J Can Assoc Radiol 24: 257-260
48. 2+-sensing receptor activates cytosolic phospholipase A2 via a Gqalpha -dependent ERK-independent pathway, J Biol Chem 276: 13941-13948
49. Hauache, OM, 2001, Extracellular calcium-sensing receptor: structural and functional features and association with diseases, Braz J Med Biol Res 34: 577-584
50. Heath, D, 1989a, Familial benign hypercalcemia, Trends Endocrinol Metab 1: 6-9
51. Heath, Hd, 1989b, Familial benign (hypocalciuric) hypercalcemia. A troublesome mimic of mild primary hyperparathyroidism, Endocrinol Metab Clin North Am 18: 723-740
52. Heath, Hd, Jackson, CE, Otterud, B and Leppert, MF, 1993, Genetic linkage analysis in familial benign (hypocalciuric) hypercalcemia: evidence for locus heterogeneity, Am J Hum Genet 53: 193-200
53. 2+-sensing receptor in the gastrointestinal tract, Cell Calcium 35: 239-247
54. Hendy, GN, D'Souza-Li, L, Yang, B, Canaff, L and Cole, DE, 2000, Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia [In Process Citation], Hum Mutat 16: 281-296
55. Hirai, H, Nakajima, S, Miyauchi, A, Nishimura, K, Shimizu, N, Shima, M, Michigami, T, Ozono, K and Okada, S, 2001, A novel activating mutation (C129S) in the calcium-sensing receptor gene in a Japanese family with autosomal dominant hypocalcemia, J Hum Genet 46: 41-44
56. Hjalm, G, MacLeod, RJ, Kifor, O, Chattopadhyay, N and Brown, EM, 2001, Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaRmediated activation of mitogen-activated protein kinase, J Biol Chem 276: 34880-34887
57. Ho, C, Conner, DA, Pollak, MR, Ladd, DJ, Kifor, O, Warren, HB, Brown, EM, Seidman, JG and Seidman, CE, 1995, A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism [see comments], Nat Genet 11: 389-394
58. 2+, J Biol Chem 280: 5113-5120
59. Huang, C, Handlogten, ME and Miller, RT, 2002, Parallel activation of phosphatidylinositol 4-kinase and phospholipase C by the extracellular calcium-sensing receptor, J Biol Chem 277: 20293-20300
60. Janicic, N, Pausova, Z, Cole, DE and Hendy, GN, 1995, Insertion of an Alu sequence in the Ca(2+)- sensing receptor gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, Am J Hum Genet 56: 880-886
61. Kanatani, M, Sugimoto, T, Kanzawa, M, Yano, S and Chihara, K, 1999, High extracellular calcium inhibits osteoclast-like cell formation by directly acting on the calcium-sensing receptor existing in osteoclast precursor cells, Biochem Biophys Res Commun 261: 144-148
62. 2+-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
63. Kifor, O, Diaz, R, Butters, R, Kifor, I and 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
64. Kifor, O, McElduff, A, LeBoff, MS, Moore, FD, Jr., Butters, R, Gao, P, Cantor, TL, Kifor, I and Brown, EM, 2004, Activating antibodies to the calcium-sensing receptor in two patients with autoimmune hypoparathyroidism, J Clin Endocrinol Metab 89: 548-556
65. Kifor, O, Moore, FD, Jr., Delaney, M, Garber, J, Hendy, GN, Butters, R, Gao, P, Cantor, TL, Kifor, I, Brown, EM and Wysolmerski, J, 2003, A syndrome of hypocalciuric hypercalcemia caused by autoantibodies directed at the calcium-sensing receptor, J Clin Endocrinol Metab 88: 60-72
66. Kobayashi, M, Tanaka, H, Tsuzuki, K, Tsuyuki, M, Igaki, H, Ichinose, Y, Aya, K, Nishioka, N and Seino, Y, 1997, Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism, J Clin Endocrinol Metab 82: 2716-2719
67. Law Jr, WM and Heath III, H, 1985, Familial benign hypercalcemia (hypocalciuric hypercalcemia). Clinical and pathogenetic studies in 21 families, Ann Int Med 105: 511-519
68. Li, Y, Song, YH, Rais, N, Connor, E, Schatz, D, Muir, A and Maclaren, N, 1996, Autoantibodies to the extracellular domain of the calcium sensing receptor in patients with acquired hypoparathyroidism., J Clin Invest 97: 910-914
69. Lienhardt, A, Bai, M, Lagarde, JP, Rigaud, M, Zhang, Z, Jiang, Y, Kottler, ML, Brown, EM and Garabedian, M, 2001, Activating mutations of the calcium-sensing receptor: management of hypocalcemia, J Clin Endocrinol Metab 86: 5313-5323
70. Lienhardt, A, Garabedian, M, Bai, M, Sinding, C, Zhang, Z, Lagarde, JP, Boulesteix, J, Rigaud, M, Brown, EM and Kottler, ML, 2000, A large homozygous or heterozygous in-frame deletion within the calcium-sensing receptor's carboxylterminal cytoplasmic tail that causes autosomal dominant hypocalcemia, J Clin Endocrinol Metab 85: 1695-1702
71. Lloyd, SE, Pannett, AA, Dixon, PH, Whyte, MP and Thakker, RV, 1999, Localization of familial benign hypercalcemia, Oklahoma variant (FBHOk), to chromosome 19q13, Am J Hum Genet 64: 189-195
72. 2+-sensing receptor with truncated C-terminal tail from the Mozambique tilapia (Oreochromis mossambicus), J Biol Chem 279: 53288-53297
73. Lorget, F, Kamel, S, Mentaverri, R, Wattel, A, Naassila, M, Maamer, M and Brazier, M, 2000, High extracellular calcium concentrations directly stimulate osteoclast apoptosis, Biochem Biophys Res Commun 268: 899-903
74. Marx, S, Attie, M, Spiegel, A, Levine, M, Lasker, R and Fox, M, 1982, An association between neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia in three kindreds, N Engl J Med 306: 257-284
75. Marx, SJ, Attie, MF, Levine, MA, Spiegel, AM, Downs Jr, RW and Lasker, RD, 1981a, The hypocalciuric or benign variant of familial hypercalcemia: clinical and biochemical features in fifteen kindreds, Medicine (Baltimore) 60: 397-412
76. Marx, SJ, Attie, MF, Stock, JL, Spiegel, AM and Levine, MA, 1981b, Maximal urine-concentrating ability: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism, J Clin Endocrinol Metab 52: 736-740
77. Marx, SJ, Fraser, D and Rapoport, A, 1985, Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes, Am J Med 78: 15-22
78. 2+ is associated with marked reduction in the expression of extracellular Ca(2+)-sensing receptor messenger ribonucleic acid and protein, Endocrinology 136: 3087-3092
79. Mizobuchi, M, Hatamura, I, Ogata, H, Saji, F, Uda, S, Shiizaki, K, Sakaguchi, T, Negi, S, Kinugasa, E, Koshikawa, S and Akizawa, T, 2004, Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency, J Am Soc Nephrol 15: 2579-2587
80. Motoyama, HI and Friedman, PA, 2002, Calcium-sensing receptor regulation of PTH-dependent calcium absorption by mouse cortical ascending limbs, Am J Physiol Renal Physiol 283: F399-406
81. Murphey, ED, Chattopadhyay, N, Bai, M, Kifor, O, Harper, D, Traber, DL, Hawkins, HK, Brown, EM and Klein, GL, 2000, 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
82. Nearing, J, Betka, M, Quinn, S, Hentschel, H, Elger, M, Baum, M, Bai, M, Chattopadyhay, N, Brown, EM, Hebert, SC and Harris, HW, 2002, Polyvalent cation receptor proteins (CaRs) are salinity sensors in fish, Proc Natl Acad Sci U S A 99: 9231-9236
83. Neer, RM, Arnaud, CD, Zanchetta, JR, Prince, R, Gaich, GA, Reginster, JY, Hodsman, AB, Eriksen, EF, Ish-Shalom, S, Genant, HK, Wang, O and Mitlak, BH, 2001, Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis, N Engl J Med 344: 1434-1441
84. 2+ in bovine parathyroid cells by external divalent cations, J Biol Chem 202: 5188-5196
85. Nemeth, EF, Fox, J, Delmar, EG, Steffey, ME, Lambert, LD, Conklin, RL, Bhatnagar, PK and Gowen, M, 1998a, Stimulation of parathyroid hormone secretion by a small molecule antagonist of the calcium receptor., J Bone Miner Res 23: S156 (absract #1030)
86. Nemeth, EF, Steffey, ME, Hammerland, LG, Hung, BC, Van Wagenen, BC, DelMar, EG and Balandrin, MF, 1998b, Calcimimetics with potent and selective activity on the parathyroid calcium receptor, Proc Natl Acad Sci U S A 95: 4040-4045
87. Ogata, H, Koiwa, F, Ito, H and Kinugasa, E, 2006, Therapeutic strategies for secondary hyperparathyroidism in dialysis patients, Ther Apher Dial 10: 355-363
88. Ogata, H, Ritz, E, Odoni, G, Amann, K and Orth, SR, 2003, Beneficial effects of calcimimetics on progression of renal failure and cardiovascular risk factors, J Am Soc Nephrol 14: 959-967
89. Ohashi, N, Uematsu, T, Nagashima, S, Kanamaru, M, Togawa, A, Hishida, A, Uchida, E, Akizawa, T and Koshikawa, S, 2004, 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
90. Okazaki, R, Chikatsu, N, Nakatsu, M, Takeuchi, Y, Ajima, M, Miki, J, Fujita, T, Arai, M, Totsuka, Y, Tanaka, K and Fukumoto, S, 1999, A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia, J Clin Endocrinol Metab 84: 363-366
91. Peacock, M, Bilezikian, JP, Klassen, PS, Guo, MD, Turner, SA and Shoback, D, 2005, Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism, J Clin Endocrinol Metab 90: 135-141
92. Pearce, S, Coulthard, M, Kendall-Taylor, P and Thakker, R, 1995a, Autosomal dominant hypocalcemia associated with a mutation in the calcium-sensing receptor, J Bone Miner Res 10: S176(Abstract 149)
93. Pearce, SH, Trump, D, Wooding, C, Besser, GM, Chew, SL, Grant, DB, Heath, DA, Hughes, IA, Paterson, CR, Whyte, MP and et al., 1995b, Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism, J Clin Invest 96: 2683-2692
94. Pearce, SH, Williamson, C, Kifor, O, Bai, M, Coulthard, MG, Davies, M, Lewis-Barned, N, McCredie, D, Powell, H, Kendall-Taylor, P, Brown, EM and Thakker, RV, 1996, A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor [see comments], N Engl J Med 335: 1115-1122
95. Pi, M, Faber, P, Ekema, G, Jackson, PD, Ting, A, Wang, N, Fontilla-Poole, M, Mays, RW, Brunden, KR, Harrington, JJ and Quarles, LD, 2005, Identification of a novel extracellular cation-sensing G-protein-coupled receptor, J Biol Chem 280: 40201-40209
96. Pi, M, Hinson, TK and Quarles, L, 1999, Failure to detect the extracellular calcium-sensing receptor (CasR) in human osteoblast cell lines, J Bone Miner Res 14: 1310-1319
97. Pollak, MR, Brown, EM, Chou, YH, Hebert, SC, Marx, SJ, Steinmann, B, Levi, T, Seidman, CE and Seidman, JG, 1993, Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, Cell 75: 1297-1303
98. Pollak, MR, Brown, EM, Estep, HL, McLaine, PN, Kifor, O, Park, J, Hebert, SC, Seidman, CE and Seidman, JG, 1994a, Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation, Nat Genet 8: 303-307
99. Pollak, MR, Chou, YH, Marx, SJ, Steinmann, B, Cole, DE, Brandi, ML, Papapoulos, SE, Menko, FH, Hendy, GN, Brown, EM and et al., 1994b, Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Effects of mutant gene dosage on phenotype, J Clin Invest 93: 1108-1112
100. Posillico, JT, Wortsman, J, Srikanta, S, Eisenbarth, GS, Mallette, LE and Brown, EM, 1986, Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells, J Bone Miner Res 1: 475-483
101. Quarles, LD, Hartle, JE, 2nd, Middleton, JP, Zhang, J, Arthur, JM and Raymond, JR, 1994, Aluminuminduced DNA synthesis in osteoblasts: mediation by a G-protein coupled cation sensing mechanism, J Cell Biochem 56: 106-117
102. 2+-sensing receptor: a target for polyamines, Am J Physiol 273: C1315-1323
103. Ray, K, Clapp, P, Goldsmith, PK and 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
104. 2+/polyvalent cation-sensing protein in rat kidney, Am J Physiol 274: F611-622
105. Riccardi, D, Lee, WS, Lee, K, Segre, GV, Brown, EM and Hebert, SC, 1996, Localization of the extracellular Ca(2+)-sensing receptor and PTH/PTHrP receptor in rat kidney, Am J Physiol 271: F951-956
106. Riccardi, D, Park, J, Lee, WS, Gamba, G, Brown, EM and Hebert, SC, 1995, Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor, Proc Natl Acad Sci U S A 92: 131-135
107. Riccardi, D, Traebert, M, Ward, DT, Kaissling, B, Biber, J, Hebert, SC and Murer, H, 2000, 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
108. Roussanne, MC, Lieberherr, M, Souberbielle, JC, Sarfati, E, Drueke, T and Bourdeau, A, 2001, Human parathyroid cell proliferation in response to calcium, NPS R-467, calcitriol and phosphate, Eur J Clin Invest 31: 610-616
109. Sanders, JL, Chattopadhyay, N, Kifor, O, Yamaguchi, T and Brown, EM, 2000, Extracellular calciumsensing 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
110. Sands, JM, Flores, FX, Kato, A, Baum, MA, Brown, EM, Ward, DT, Hebert, SC and Harris, HW, 1998, Vasopressin-elicited water and urea permeabilities are altered in IMCD in hypercalcemic rats, Am J Physiol 274: F978-985
111. Sands, JM, Naruse, M, Baum, M, Jo, I, Hebert, SC, Brown, EM and Harris, HW, 1997, Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct, J Clin Invest 99: 1399-1405
112. 2+-sensing receptor gene in three Danish families, Scand J Clin Lab Invest 60: 221-227
113. Schwarz, P, Sorensen, HA, McNair, P and Transbol, I, 1993, Cica-clamp technique: a method for quantifying parathyroid hormone secretion: a sequential citrate and calcium clamp study, Eur J Clin Invest 23: 546-553
114. Shalhoub, V, Grisanti, M, Padagas, J, Scully, S, Rattan, A, Qi, M, Varnum, B, Vezina, C, Lacey, D and Martin, D, 2003, In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult osteoblastic and osteoclastic cells, Crit Rev Eukaryot Gene Expr 13: 89-106
115. Shoback, DM, Membreno, LA and McGhee, JG, 1988, High calcium and other divalent cations increase inositol trisphosphate in bovine parathyroid cells, Endocrinology 123: 382-389
116. 2+ binding pocket within the venus flytrap module of the human calcium-sensing receptor, J Biol Chem 280: 37917-37923
117. Simonds, WF, James-Newton, LA, Agarwal, SK, Yang, B, Skarulis, MC, Hendy, GN and Marx, SJ, 2002, Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds, Medicine (Baltimore) 81: 1-26
118. Soderbergh, A, Myhre, AG, Ekwall, O, Gebre-Medhin, G, Hedstrand, H, Landgren, E, Miettinen, A, Eskelin, P, Halonen, M, Tuomi, T, Gustafsson, J, Husebye, ES, Perheentupa, J, Gylling, M, Manns, MP, Rorsman, F, Kampe, O and Nilsson, T, 2004, Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I, J Clin Endocrinol Metab 89: 557-562
119. Tfelt-Hansen, J and Brown, EM, 2005, The calcium-sensing receptor in normal physiology and pathophysiology: a review, Crit Rev Clin Lab Sci 42: 35-70
120. Tfelt-Hansen, J, Chattopadhyay, N, Yano, S, Kanuparthi, D, Rooney, P, Schwarz, P and Brown, EM, 2004, 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
121. Wada, M, Ishii, H, Furuya, Y, Fox, J, Nemeth, EF and Nagano, N, 1998, NPS R-568 halts or reverses osteitis fibrosa in uremic rats [see comments], Kidney Int 53: 448-453
122. Wada, M, Nagano, N, Furuya, Y, Chin, J, Nemeth, EF and Fox, J, 2000, Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism, Kidney Int 57: 50-58
123. Ward, DT and Riccardi, D, 2002, Renal physiology of the extracellular calcium-sensing receptor, Pflugers Arch 445: 169-176
124. Warner, J, Epstein, M, Sweet, A, Singh, D, Burgess, J, Stranks, S, Hill, P, Perry-Keene, D, Learoyd, D, Robinson, B, Birdsey, P, Mackenzie, E, Teh, BT, Prins, JB and Cardinal, J, 2004, Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications, J Med Genet 41: 155-160
125. Wellendorph, P and Brauner-Osborne, H, 2004, Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor, Gene 335: 37-46
126. Wellendorph, P, Hansen, KB, Balsgaard, A, Greenwood, JR, Egebjerg, J and Brauner-Osborne, H, 2005, Deorphanization of GPRC6A: a promiscuous L-alpha-amino acid receptor with preference for basic amino acids, Mol Pharmacol 67: 589-597
127. Wettschureck, N, Lee, E, Libutti, SK, Offermanns, S, Robey, PG and Spiegel, AM, 2006, Parathyroidspecific double knockout of Gq- and G11-{alpha} subunits leads to a phenotype resembling germline knockout of the extracellular Ca++-sensing receptor, Mol Endocrinol
128. Winer, KK, Yanovski, JA, Sarani, B and Cutler, GB, Jr., 1998, A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism, J Clin Endocrinol Metab 83: 3480-3486
129. 2+ sensing receptor activation in the growth plate, Faseb J 18: 143-145
130. Yamaguchi, T, Ye, C, Chattopadhyay, N, Sanders, JL, Vassilev, PM and Brown, EM, 2000, Enhanced expression of extracellular calcium sensing receptor in monocyte-differentiated versus undifferentiated HL-60 cells: potential role in regulation of a nonselective cation channel [In Process Citation], Calcif Tissue Int 66: 375-382
131. Yamamoto, M, Akatsu, T, Nagase, T and Ogata, E, 2000, Comparison of hypocalcemic hypercalciuria between patients with idiopathic hypoparathyroidism and those with gain-of-function mutations in the calcium-sensing receptor: is it possible to differentiate the two disorders?, J Clin Endocrinol Metab 85: 4583-4591
132. Yarden, N, Lavelin, I, Genina, O, Hurwitz, S, Diaz, R, Brown, EM and Pines, M, 2000, Expression of calcium-sensing receptor gene by avian parathyroid gland in vivo: relationship to plasma calcium, Gen Comp Endocrinol 117: 173-181
133. Ye, C, Ho-Pao, CL, Kanazirska, M, Quinn, S, Rogers, K, Seidman, CE, Seidman, JG, Brown, EM and Vassilev, PM, 1997, Amyloid-beta proteins activate Ca(2+)-permeable channels through calciumsensing receptors, J Neurosci Res 47: 547-554
134. Zaidi, M, Adebanjo, OA, Moonga, BS, Sun, L and Huang, CL, 1999, Emerging insights into the role of calcium ions in osteoclast regulation, J Bone Miner Res 14: 669-674
135. Zhang, M and Breitwieser, GE, 2005, High affinity interaction with filamin A protects against calciumsensing receptor degradation, J Biol Chem 280: 11140-11146
136. Zhang, Z, Qiu, W, Quinn, SJ, Conigrave, AD, Brown, EM and Bai, M, 2002, Three adjacent serines in the extracellular domains of the CaR are required for L-amino acid-mediated potentiation of receptor function, J Biol Chem 277: 33727-33735