Skip to main content
SpringerLink
Log in

An Overview of Extracellular Calcium Homeostasis and the Roles of the CaR in Parathyroid and C-cells

  • Chapter
Calcium-Sensing Receptor

Part of the book series: Endocrine updates ((ENDO,volume 19))

Abstract

Calcium ions are of vital importance for the human body. Both within the outside of the cell, calcium (Ca2+) plays key roles in numerous crucial physiological processes. Intracellular calcium is vital for regulating myriad cellular functions, such as differentiation, secretion, proliferation and motility, and it also acts as a cofactor in numerous enzymatic reactions (1). Equally importantly, it serves as an intracellular second messenger for a variety of receptor-mediated events. The levels of free calcium in the cytosol (Ca2+ i), although dependent to some extent on extracellular calcium (Ca2+ o), are much lower than the latter (100 nM vs. 1.1–1.3 mM) (2,3). Quite unlike Ca2+ o, Ca2+ i fluctuates rapidly and over a wide range (10-fold or more) in response to hormonal and other stimuli (3).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Berridge M, Lipp M, Bootman M 1999 Calcium signalling. Curr Biol 9:R157–159

    Article  PubMed  CAS  Google Scholar 

  2. Brown EM 1991 Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messengers. Physiol Rev 71:371–411

    PubMed  CAS  Google Scholar 

  3. Pozzan T, Rizzuto R, Volpe P, Meldolesi J 1994 Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 74:595–636

    Article  PubMed  CAS  Google Scholar 

  4. Brown EM Physiology of Calcium homeostasis. In: Biliezikian JP, Raisz LG, Rodan G, eds. The Parathyroids, 2 edn. San Diego: Academic Press, 2001: 167–181

    Chapter  Google Scholar 

  5. Bringhurst FR, Demay MB, Kronenberg HM Hormones and disorders of mineral metabolism. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR, eds. Williams Textbook of Endocrinology, 9th edn. Philadelphia: W.B. Saunders, 1998:1155–1209

    Google Scholar 

  6. 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

    Article  PubMed  CAS  Google Scholar 

  7. Quarles LD 1997 Cation-sensing receptors in bone: A novel paradigm for regulating bone remodeling? J Bone Miner Res 12:1971–1974

    Article  PubMed  CAS  Google Scholar 

  8. Hoare SR, Usdin TD 2001 Molecular mechanisms of ligand recognition by parathyroid hormone 1 (PTH1) and PTH2 receptors. Curr Pharm Res 7:689–713

    Article  CAS  Google Scholar 

  9. Abou-Samra A, Juppner H, Force T, Freeman MW, Kong X, Schipani E, Segre G, Kronenberg H 1992 Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol phosphates and increases intracellular freee calcium. Proc Natl Acad Sci USA 89:2732–2736

    Article  PubMed  CAS  Google Scholar 

  10. Khosla S 2001 The OPG/RANK/RANK ligand system. Endocrinology 142:5050–5055

    Article  PubMed  CAS  Google Scholar 

  11. D’Amour P 2002 Effects of acute and chronic hypercalcemia on parathyroid function and circulating parathyroid hormone molecular forms. Eur J Endocrinol 146:407–410

    Article  PubMed  Google Scholar 

  12. Russell J, Lettieri DF, Sherwood LM 1983 Direct regulation by calcium of cytoplasmic messenger ribonucleic acid coding for preproparathyroid hormone in isolated bovine parathyroid cells. J Clin Invest 72:1851–1855

    Article  PubMed  CAS  Google Scholar 

  13. Yamamoto M, Igarishi T, Muramatsu M, Fukagawa M, Motokura T, Ogata E 1989 Hypocalcemia increases and hypercalcemia decreases the steady state level of parathyroid hormone messenger RNA in the rat. J Clin Invest 83:1053–1056

    Article  PubMed  CAS  Google Scholar 

  14. Silver J, Sela SB, Naveh-Many T 1997 Regulation of parathyroid cell proliferation. Curr Opin Nephrol Hypertens 6:321–326.

    Article  PubMed  CAS  Google Scholar 

  15. Silver J, Naveh-Many T, Mayer H, Schmelzer HJ, Popovtzer MM 1986 Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat. J Clin Invest 78:1296–1301

    Article  PubMed  CAS  Google Scholar 

  16. Russell J, Sherwood LM 1987 The effects of 1,25-dihydroxyvitamin D3 and high calcium on transcription of the pre-proparathyroid hormone gene are direct. Trans Assoc Am Physicians 100:256–262

    PubMed  CAS  Google Scholar 

  17. Brent GA, LeBoff MS, Seely EW, Conlin PR, Brown EM 1988 Relationship between the concentration and rate of change of calcium and serum intact parathyroid hormone levels in normal humans. J Clin Endocrinol Metab 67:944–950

    Article  PubMed  CAS  Google Scholar 

  18. Brown EM, Leombruno R, Thatcher J, Burrowes M 1985 The acute secretory response to alterations in the extracellular calcium concentration and dopamine in perifused bovine parathyroid cells. Endocrinology 116:1123–1132

    Article  PubMed  CAS  Google Scholar 

  19. Hanley D, Takatsuki K, Sultan J, Schneider A, Sherwood L 1978 Direct release of parathyroid hormone fragments from functioning bovine parathyroid glands in vitro. J Clin Invest 62:1247–1254

    Article  PubMed  CAS  Google Scholar 

  20. Sela-Brown A, Naveh-Many T, Silver J 1999 transcriptional and post-transcriptional regulation of PTH gene expression by vitamin D, calcium and phosphate. Miner Electrolyte Metab 25:342–344

    Article  PubMed  CAS  Google Scholar 

  21. Silver J, Moallem E, Epstein E, Kilav R, Naveh-Many T 1994 New aspects in the control of parathyroid hormone secretion. Curr Opin Nephrol Hypertens 3:379–385

    Article  PubMed  CAS  Google Scholar 

  22. Mayer GP, Habener JF, Potts Jr J 1979 Parathyroid hormone secretion in vivo: demonstration of a calcium-independent, non-suppressible component of secretion. J Clin Invest 57:678–683

    Article  Google Scholar 

  23. Brown EM 1983 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

    Article  PubMed  CAS  Google Scholar 

  24. Brown EM 2000 Familial hypocalciuric hypercalcemia and other disorders with resistance to extracellular calcium. Endocrinol Metab Clin North Am 29:503–522

    Article  PubMed  CAS  Google Scholar 

  25. Hauache OM 2001 Extracellular calcium-sensing receptor: structural and functional features and association with diseases. Braz J Med Biol Res 34:577–584

    Article  PubMed  CAS  Google Scholar 

  26. Conlin PR, Fajtova VT, Mortensen RM, LeBoff MS, Brown EM 1989 Hysteresis in the relationship between serum ionized calcium and intact parathyroid hormone during recovery from induced hyper-and hypocalcemia in normal humans. J Clin Endocrinol Metab 69:593–599

    Article  PubMed  CAS  Google Scholar 

  27. Grant FD, Conlin PR, Brown EM 1990 Rate and concentration dependence of parathyroid hormone dynamics during stepwise changes in serum ionized calcium in normal humans. J Clin Endocrinol Metab 71:370–378

    Article  PubMed  CAS  Google Scholar 

  28. Brown E, Enyedi P, LeBoff M, Rotberg J, Preston J, Chen C 1987 High extracellular Ca2+ and Mg2+ stimulate accumulation of inositol phosphates in bovine parathyroid cells. FEBS Lett 218:113–118

    Article  PubMed  CAS  Google Scholar 

  29. Nemeth E, Scarpa A 1987 Rapid mobilization of cellular Ca2+ in bovine parathyroid cells by external divalent cations. J Biol Chem 202:5188–5196

    Google Scholar 

  30. Chen C, Barnett J, Congo D, Brown E 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

    Article  PubMed  CAS  Google Scholar 

  31. El-Hajj Fuleihan G, Brown EM 1990 Effect of the lectin concanavalin-A on calcium-regulated adenosine 3′,5′-monophosphate accumulation in bovine parathyroid cells. Endocrinology 126:1996–2002

    Article  PubMed  CAS  Google Scholar 

  32. Kifor O, Congo D, Brown EM 1990 Phorbol esters modulate the high Ca2+-stimulated accumulation of inositol phosphates in bovine parathyroid cells. J Bone Miner Res 5:1003–1011

    Article  PubMed  CAS  Google Scholar 

  33. Nygren P, Gylfe E, Larsson R, Johansson H, Juhlin C, Klareskoq L, Akerstrom G, Rastad J 1988 Modulation of the Ca2+-sensing function of parathyroid cells in vitro and in hyperparathyroidism. Biochim Biophys Acta 968:253–260

    Article  PubMed  CAS  Google Scholar 

  34. Racke F, Hammerland L, Dubyak G, Nemeth E 1993 Functional expression of the parathyroid cell calcium receptor in Xenopus oocytes. FEBS Lett 333:132–136

    Article  PubMed  CAS  Google Scholar 

  35. Chen TH, Pratt SA, Shoback DM 1994 Injection of bovine parathyroid poly(A+) RNA into Xenopus oocytes confers sensitivity to high extracellular calcium. J Bone Miner Res 9:293–300

    Article  PubMed  CAS  Google Scholar 

  36. 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 U S A 92:131–135

    Article  PubMed  CAS  Google Scholar 

  37. Garrett JE, Tamir H, Kifor O, Simin RT, Rogers KV, Mithal A, Gagel RF, Brown EM 1995 Calcitonin-secreting cells of the thyroid express an extracellular calcium receptor gene. Endocrinology 136:5202–5211

    Article  PubMed  CAS  Google Scholar 

  38. 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, 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

    Article  PubMed  CAS  Google Scholar 

  39. Garrett JE, Capuano IV, Hammerland LG, Hung BCP, 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

    Article  PubMed  CAS  Google Scholar 

  40. Freichel M, Zink-Lorenz A, Holloschi A, Hafner M, Flockerzi V, Raue F 1996 Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology 137:3842–3848

    Article  PubMed  CAS  Google Scholar 

  41. 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

    Article  PubMed  CAS  Google Scholar 

  42. Bai M, Trivedi S, Brown EM 1998 Dimerization of the extracellular calcium-sensing receptor (CaR) on the cell surface of CaR-transfected HEK293 cells. J Biol Chem 273:23605–23610

    Article  PubMed  CAS  Google Scholar 

  43. Bai M, Trivedi S, Kifor O, Quinn SJ, Brown EM 1999 Intermolecular interactions between dimeric calcium-sensing receptor monomers are important for its normal function. Proc Natl Acad Sci U S A 96:2834–2839

    Article  PubMed  CAS  Google Scholar 

  44. Pin J, Duvoisin R 1995 The metabotropic glutamate receptors-structure and functions. Neuropharmacol 34:1–26

    Article  CAS  Google Scholar 

  45. Bowery NG, Brown DA 1997 The cloning of GABA(B) receptors. Nature 386:239–246

    Article  Google Scholar 

  46. Matsunami H, Buck LB 1997 A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90:775–784.

    Article  PubMed  CAS  Google Scholar 

  47. Mombaerts P 1999 Molecular biology of odorant receptors in vertebrates. Annu Rev Neurosci 22:487–509

    Article  PubMed  CAS  Google Scholar 

  48. Hoon MA, Adler E, Lindemeier J, Battey JF, Ryba NJ, Zuker CS 1999 Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell 96:541–551

    Article  PubMed  CAS  Google Scholar 

  49. Shilton BH, Flocco MM, Nilsson M, Mowbray SL 1996 Conformational changes of three periplasmic receptors for bacterial Chemotaxis and transport: the maltose-, glucose/galactose-and ribose-binding proteins. J Mol Biol 264:350–363

    Article  PubMed  CAS  Google Scholar 

  50. Olszak IT, Poznansky MC, Evans RH, Olson D, Kos C, Pollak MR, Brown EM, Scadden DT 2000 Extracellular calcium elicits a chemokinetic response from monocytes in vitro and in vivo. J Clin Invest 105:1299–1305

    Article  PubMed  CAS  Google Scholar 

  51. 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

    Article  PubMed  CAS  Google Scholar 

  52. 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

    Article  PubMed  CAS  Google Scholar 

  53. 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

    Article  PubMed  CAS  Google Scholar 

  54. 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:F291–302

    PubMed  CAS  Google Scholar 

  55. Awata H, Huang C, Handlogten ME, Miller RT 2001 Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein. J Biol Chem 276:34871–34879

    Article  PubMed  CAS  Google Scholar 

  56. 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:R1008–1016

    PubMed  CAS  Google Scholar 

  57. 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

    Article  PubMed  CAS  Google Scholar 

  58. Diaz R, El-Hajj Fuleihan G, Brown EM: Regulation of parathyroid function. In: Fray J, ed. Handbook of Physiology. section 7:, Endocrinology, Vol. III. Hormonal regulation of water and electrolyte balance. New York: Oxford University Press, 1998:607–662

    Google Scholar 

  59. Corbetta S, Lania A, Filopanti M, Vincentini L, Ballare E, Spada A 2002 Mitogen-activated protein kinase cascade in human normal and tumoral parathyroid cells. J Clin Endocrinol Metab 87:2201–2205

    Article  PubMed  CAS  Google Scholar 

  60. Thogeirsson U, Costa J, Marx SJ 1981 The parathyroid glands in familial hypocalciuric hypercalcemia. Hum Pathol 12:229–237

    Article  Google Scholar 

  61. Wada M, Nagano N, Furuya Y, Chin J, Nemeth EF, Fox J 2000 Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. Kidney Int 57:50–58

    Article  PubMed  CAS  Google Scholar 

  62. Garrett J, Steffey M, Nemeth E 1995 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)

    Google Scholar 

  63. LeBoff MS, Rennke HG, Brown EM 1983 Abnormal regulation of parathyroid cell secretion and proliferation in primary cultures of bovine parathyroid cells. Endocrinology 113:277–284

    Article  PubMed  CAS  Google Scholar 

  64. Mithal A, Kifor O, Kifor I, Vassilev P, Butters R, Krapcho K, Simin R, Fuller F, Hebert SC, Brown EM 1995 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

    Article  PubMed  CAS  Google Scholar 

  65. Brown AJ, Zhong M, Ritter C, Brown EM, 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

    Article  PubMed  CAS  Google Scholar 

  66. Roussanne MC, Gogusev J, Hory B, Duchambon P, Souberbielle JC, Nabarra B, Pierrat D, Sarfati E, Drueke T, Bourdeau A 1998 Persistence of Ca2+-sensing receptor expression in functionally active, long-term human parathyroid cell cultures. J Bone Miner Res 13:354–362

    Article  PubMed  CAS  Google Scholar 

  67. Bai M, Quinn S, Trivedi S, Kifor O, Pearce SHS, Pollak MR, Krapcho K, Hebert SC, Brown EM 1996 Expression and characterization of inactivating and activating mutations in the human Ca2+ o-sensing receptor. J Biol Chem 271:19537–19545

    Article  PubMed  CAS  Google Scholar 

  68. Bai M, Pearce SH, Kifor O, Trivedi S, Stauffer UG, Thakker RV, Brown EM, Steinmann B 1997 In vivo and in vitro characterization of neonatal hyperparathyroidism resulting from a de novo, 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

    Article  PubMed  CAS  Google Scholar 

  69. Pollak MR, Brown EM, Estep HL, McLaine PN, Kifor O, Park J, Hebert SC, Seidman CE, Seidman JG 1994 Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. Nat Genet 8:303–307

    Article  PubMed  CAS  Google Scholar 

  70. Kifor O, Moore FD, Jr., Wang P, Goldstein M, Vassilev P, Kifor I, Hebert SC, Brown EM 1996 Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab 81:1598–1606

    Article  PubMed  CAS  Google Scholar 

  71. Corbetta S, Mantovani G, Lania A, Borgato S, Vicentini L, Beretta E, Faglia G, Di Blasio AM, Spada A 2000 Calcium-sensing receptor expression and signalling in human parathyroid adenomas and primary hyperplasia. Clin Endocrinol (Oxf) 52:339–348

    Article  CAS  Google Scholar 

  72. Gogusev J, Duchambon P, Hory B, Giovannini M, Goureau Y, Sarfati E, Drueke TB 1997 Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 51:328–336

    Article  PubMed  CAS  Google Scholar 

  73. Cetani F, Picone A, Cerrai P, Vignali E, Borsari S, Pardi E, Viacava P, Naccarato AG, Miccoli P, Kifor O, Brown EM, Pinchera A, Marcocci C 2000 Parathyroid expression of calcium-sensing receptor protein and in vivo parathyroid hormone-Ca(2+) set-point in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 85:4789–4794

    Article  PubMed  CAS  Google Scholar 

  74. Sudhaker Rao D, Han ZH, Phillips ER, Palnitkar S, Parfitt AM 2000 Reduced vitamin D receptor expression in parathyroid adenomas: implications for pathogenesis. Clin Endocrinol (Oxf) 53:373–381

    Article  CAS  Google Scholar 

  75. 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.

    Article  PubMed  CAS  Google Scholar 

  76. Cetani F, Pinchera A, Pardi E, Cianferotti L, Vignali E, Picone A, Miccoli P, Viacava P, Marcocci C 1999 No evidence for mutations in the calcium-sensing receptor gene in sporadic parathyroid adenomas. J Bone Miner Res 14:878–882

    Article  PubMed  CAS  Google Scholar 

  77. Hosokawa Y, Pollak MR, Brown EM, Arnold A 1995 Mutational analysis of the extracellular Ca(2+)-sensing receptor gene in human parathyroid tumors. J Clin Endocrinol Metab 80:3107–3110

    Article  PubMed  CAS  Google Scholar 

  78. 78._Yano S, Sugimoto T, Tsukamoto T, Chihara K, Kobayashi A, Kitazawa S, Maeda S, Kitazawa R 2000 Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism. Kidney Int 5 8:1980-1986

    Google Scholar 

  79. Yano S, Sugimoto T, Kanzawa M, Tsukamoto T, Hattori T, Hattori S, Chihara K 2000 Association of polymorphic alleles of the calciumsensing receptor gene with parathyroid hormone secretion in hemodialysis patients. Nephron 85:317–323

    Article  PubMed  CAS  Google Scholar 

  80. Brown AJ, Zhong M, Finch J, Ritter C, McCracken R, Morrissey J, Slatopolsky E 1996 Rat calcium-sensing receptor is regulated by vitamin D but not by calcium. Am J Physiol 270:F454–460

    PubMed  CAS  Google Scholar 

  81. Rogers KV, Dunn CK, Conklin RL, Hadfield S, Petty BA, Brown EM, Hebert SC, Nemeth EF, Fox J 1995 Calcium receptor messenger ribonucleic acid levels in the parathyroid glands and kidney of vitamin D-deficient rats are not regulated by plasma calcium or 1,25-dihydroxyvitamin D3. Endocrinology 136:499–504

    Article  PubMed  CAS  Google Scholar 

  82. Brown A J, Zhong M, Finch J, Ritter C, Slatopolsky E 1995 The roles of calcium and 1,25-dihydroxy vitamin D3 in the regulation of vitamin D receptor expression by rat parathyroid glands. Endocrinology 136:1419–1425

    Article  PubMed  CAS  Google Scholar 

  83. Yarden N, Lavelin I, Genina O, Hurwitz S, Diaz R, Brown EM, 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

    Article  PubMed  CAS  Google Scholar 

  84. Suzuki K, Lavaroni S, Mori A, Okajima F, Kimura S, Katoh R, Kawaoi A, Kohn LD 1998 Thyroid transcription factor 1 is calcium modulated and coordinately regulates genes involved in calcium homeostasis in C cells. Mol Cell Biol 18:7410–7422

    PubMed  CAS  Google Scholar 

  85. Mantovani G, Corbetta S, Romoli R, Alberti L, Beck-Peccoz P, Spada A 2001 Absence of thyroid transcription factor-1 expression in human parathyroid and pituitary glands. Mol Cell Endocrinol 182:13–17

    Article  PubMed  CAS  Google Scholar 

  86. Brown A J, Ritter CS, Finch JL, Slatopolsky EA 1999 Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: role of dietary phosphate. Kidney Int 55:1284–1292

    Article  PubMed  CAS  Google Scholar 

  87. Hernandez A, Torres A, Conception MT, Salido E 1996 Parathyroid gland calcium receptor gene expression is not regulated by increased dietary phosphorus in normal and renal failure rats. Nephrol Dial Transplant 11:11–14

    Article  PubMed  CAS  Google Scholar 

  88. Ritter CS, Finch JL, Slatopolsky EA, Brown AJ 2001 Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor. Kidney Int 60:1737–1744

    Article  PubMed  CAS  Google Scholar 

  89. Nielsen PK, Rasmussen AK, Butters R, Feldt-Rasmussen U, Bendtzen K, Diaz R, Brown EM, Olgaard K 1997 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

    Article  PubMed  CAS  Google Scholar 

  90. Murphey ED, Chattopadhyay N, Bai M, Kifor O, Harper D, Traber DL, Hawkins HK, Brown EM, 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

    Article  PubMed  CAS  Google Scholar 

  91. Fried R, Tashjian AJ 1986 Unusual sensitivity of cytosolic free Ca2+ to changes in extracellular Ca2+ in rat C-cells. J Biol Chem 261:7669–7674.

    PubMed  CAS  Google Scholar 

  92. Fajtova V, Quinn S, Brown E 1991 Cytosolic calcium responses of single rMTC 44-2 cells to stimulation with external calcium and potassium. Am J Physiol 261:E151–158

    PubMed  CAS  Google Scholar 

  93. Scherubl H, Kleppisch T, Zink A, Raue F, Krautwurst D, Hescheler J 1993 Major role of dihydropyridine-sensitive Ca2+ channels in Ca2+-induced calcitonin secretion. Am J Physiol 264:E354–360

    PubMed  CAS  Google Scholar 

  94. Douglas WW, Stimulus-secretion coupling: Variations on the theme of calcium activated exocytosis involving cellular and extracellular sources of calcium. In: vol Ciba Foundation Symposium, 1978: 61–90

    Google Scholar 

  95. Muff R, Nemeth EF, Haller-Brem S, Fischer JA 1988 Regulation of hormone secretion and cytosolic Ca2+ by extracellular Ca2+ in parathyroid cells and C-cells: Role of voltage-sensitive Ca2+ channels. Arch Biochem Biophys 265:128–135

    Article  PubMed  CAS  Google Scholar 

  96. Nemeth EF, Scarpa A 1986 Cytosolic Ca2+ and the regulation of secretion in parathyroid cells. FEBS Lett 203:15–19

    Article  PubMed  CAS  Google Scholar 

  97. Eskert R, Scherubl H, Petzelt C, Friedhelm R, Ziegler R 1989 Rhythmic oscillations of cytosolic calcium in rat C-cells. Mol Cell Endocrinol 64:267–270

    Article  Google Scholar 

  98. Miki H, Maercklein PB, Fitzpatrick LA 1995 Spontaneous oscillations of intracellular calcium in single bovine parathyroid cells may be associated with the inhibition of parathyroid-hormone secretion. Endocrinology 136:2954–2959

    Article  PubMed  CAS  Google Scholar 

  99. Chang W, Chen TH, Gardner P, Shoback D 1995 Regulation of Ca2+-conducting currents in parathyroid cells by extracellular Ca2+ and channel blockers. Am J Physiol 269:E864–877

    PubMed  CAS  Google Scholar 

  100. Pocotte S, Ehrenstein G, Fitzpatrick L 1995 Role of calcium channels in parathyroid hormone secretion. Bone 16:S365–S372

    Google Scholar 

  101. McGehee DS, Aldersberg M, Liu KP, Hsuing S, Heath MJ, Tamir H 1997 Mechanism of extracellular Ca2+ receptor-stimulated hormone release from sheep thyroid parafollicular cells. J Physiol (Lond) 502:31–44

    Article  CAS  Google Scholar 

  102. Tamir H, Liu KP, Aldersberg M, Hsuiung SC, Gershon MD 1996 Acidification of serotonin-containing secretory vesicles induced by a plasma membrane calcium receptor. J Biol Chem 271:6441–6450

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrinology and Diabetes Department, Indraprastha Apollo Hospitals, New Delhi, India

    Ambrish Mithal M.D.

  2. Endocrine-Hypertension Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Edward M. Brown M.D.

Authors
  1. Ambrish Mithal M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edward M. Brown M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Endocrine-Hypertension Division Department of Medicine, Brigham and Women’s Hospital Harvard Medical School, Boston, Massachusetts, USA

    Naibedya Chattopadhyay  & Edward M. Brown  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Mithal, A., Brown, E.M. (2003). An Overview of Extracellular Calcium Homeostasis and the Roles of the CaR in Parathyroid and C-cells. In: Chattopadhyay, N., Brown, E.M. (eds) Calcium-Sensing Receptor. Endocrine updates, vol 19. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9256-7_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9256-7_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4861-0

  • Online ISBN: 978-1-4419-9256-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation