View More View Less
  • 1 Semmelweis Egyetem, Általános Orvostudományi Kar II. Belgyógyászati Klinika Budapest Szentkirályi u. 46. 1088
  • 2 Magyar Tudományos Akadémia és Semmelweis Egyetem Molekuláris Medicina Kutatócsoport Budapest
Open access

Régóta ismert, hogy az ionos kalcium fontos sejten belüli másodlagos hírvivő szerepet tölt be. Az utóbbi 15 évben megismert kísérletes vizsgálatok és klinikai tanulmányok eredményei alapján az is egyértelművé vált, hogy az ionos kalcium elsődleges jelként is működik: az extracelluláris kalciumion egy G-fehérjéhez kapcsolódó sejtfelszíni receptort aktivál, amit kalciumérzékelő receptornak neveztek el. A szerzők összefoglalják a kalciumérzékelő receptor szerepét a kalciumhomeosztázis fenntartásában, ismertetik a receptor működésének szövetspecifikus sajátosságait és azokat a kórképeket, amelyek a kalciumérzékelés zavarával járnak. A kalciumérzékelő receptor génjének funkcióvesztést vagy fokozott működést okozó csírasejtes mutációi hyper- vagy hypocalcaemiával járó öröklődő betegségeket váltanak ki. Az inaktiváló hatású mutációk heterozigóta formában familiáris hypocalciuriás hypercalcaemiát, míg homozigóta formában a gyakran életet veszélyeztető újszülöttkori hyperparathyreosist okozzák. Az autoszomális domináns hypocalcaemia hátterében aktiváló mutációk állnak. A szerzők összefoglalják ezeknek a betegségeknek a klinikai és laboratóriumi jellemzőit és a kezelés lehetőségeit. Áttekintik azokat a molekuláris folyamatokat, amelyek primer és szekunder hyperparathyreosisos betegekben hibás kalciumérzékelést váltanak ki, valamint azokat a klinikai vizsgálatokat, amelyek a kalciumérzékelő receptorgén genetikai variációinak funkcionális következményeiről számolnak be.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Brown, E. M.: 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., 1983, 56 , 572–581.

    Brown E. M. , 'Four-parameter model of the sigmoidal relationship between parathyroid hormone release and extracellular calcium concentration in normal and abnormal parathyroid tissue ' (1983 ) 56 J. Clin. Endocrinol. Metab. : 572 -581.

    • Search Google Scholar
  • Brown, E., Enyedi, P., LeBoff, M. és mtsai: High extracellular Ca 2+ and Mg 2+ stimulate accumulation of inositol phosphates in bovine parathyroid cells. FEBS Lett., 1987, 218 , 113–118.

    LeBoff M. , 'High extracellular Ca2+ and Mg2+ stimulate accumulation of inositol phosphates in bovine parathyroid cells ' (1987 ) 218 FEBS Lett. : 113 -118.

    • Search Google Scholar
  • Brown, E. M., Gamba, G., Riccardi, D. és mtsai: Cloning and characterization of an extracellular Ca 2+ -sensing receptor from bovine parathyroid. Nature, 1993, 366 , 575–580.

    Riccardi D. , 'Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid ' (1993 ) 366 Nature : 575 -580.

    • Search Google Scholar
  • Garrett, J. E., Capuano, I. V., Hammerland, L. G. és mtsai: Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. J. Biol. Chem., 1995, 270 , 12919–12925.

    Hammerland L. G. , 'Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs ' (1995 ) 270 J. Biol. Chem. : 12919 -12925.

    • Search Google Scholar
  • Janicic, N., Soliman, E., Pausova, Z. és mtsai: Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16. Mamm. Genome, 1995, 6 , 798–801.

    Pausova Z. , 'Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16 ' (1995 ) 6 Mamm. Genome : 798 -801.

    • Search Google Scholar
  • Brauner-Osborne, H., Jensen, A. A., Sheppard, P. O. és mtsai: Cloning and characterization of a human orphan family C G-protein coupled receptor GPRC5D. Biochim. Biophys. Acta, 2001, 1518 , 237–248.

    Sheppard P. O. , 'Cloning and characterization of a human orphan family C G-protein coupled receptor GPRC5D ' (2001 ) 1518 Biochim. Biophys. Acta : 237 -248.

    • Search Google Scholar
  • Fan, G., Goldsmith, P. K., Collins, R. és mtsai: N-linked glycosylation of the human Ca 2+ receptor is essential for its expression at the cell surface. Endocrinology, 1997, 138 , 1916–1922.

    Collins R. , 'N-linked glycosylation of the human Ca2+ receptor is essential for its expression at the cell surface ' (1997 ) 138 Endocrinology : 1916 -1922.

    • Search Google Scholar
  • Pace, A. J., Gama, L., Breitwieser, G. E.: Dimerization of the calcium-sensing receptor occurs within the extracellular domain and is eliminated by Cys → Ser mutations at Cys101 and Cys236. J. Biol. Chem., 1999, 274 , 11629–11634.

    Breitwieser G. E. , 'Dimerization of the calcium-sensing receptor occurs within the extracellular domain and is eliminated by Cys → Ser mutations at Cys101 and Cys236 ' (1999 ) 274 J. Biol. Chem. : 11629 -11634.

    • Search Google Scholar
  • Bouschet, T., Martin, S., Henley, J. M.: Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane. J. Cell Sci., 2005, 118 , 4709–4720.

    Henley J. M. , 'Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane ' (2005 ) 118 J. Cell Sci. : 4709 -4720.

    • Search Google Scholar
  • Silve, C., Petrel, C., Leroy, C. és mtsai: Delineating a Ca 2+ binding pocket within the venus flytrap module of the human calcium-sensing receptor. J. Biol. Chem., 2005, 280 , 37917–37923.

    Leroy C. , 'Delineating a Ca2+ binding pocket within the venus flytrap module of the human calcium-sensing receptor ' (2005 ) 280 J. Biol. Chem. : 37917 -37923.

    • Search Google Scholar
  • Huang, Y., Zhou, Y., Castiblanco, A. és mtsai: Multiple Ca 2+ -binding sites in the extracellular domain of the Ca 2+ -sensing receptor corresponding to cooperative Ca 2+ response. Biochemistry, 2009, 48 , 388–398.

    Castiblanco A. , 'Multiple Ca2+-binding sites in the extracellular domain of the Ca2+-sensing receptor corresponding to cooperative Ca2+ response ' (2009 ) 48 Biochemistry : 388 -398.

    • Search Google Scholar
  • Chang, W., Shoback, D.: Extracellular Ca 2+ -sensing receptors – an overview. Cell Calcium, 2004, 35 , 183–196.

    Shoback D. , 'Extracellular Ca2+-sensing receptors – an overview ' (2004 ) 35 Cell Calcium : 183 -196.

    • Search Google Scholar
  • Hu, J., Spiegel, A. M.: Naturally occurring mutations of the extracellular Ca 2+ -sensing receptor: implications for its structure and function. Trends Endocrinol. Metab., 2003, 14 , 282–288.

    Spiegel A. M. , 'Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function ' (2003 ) 14 Trends Endocrinol. Metab. : 282 -288.

    • Search Google Scholar
  • Ramirez, J. A., Goodman, W. G., Gornbein, J. és mtsai: Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism. J. Clin. Endocrinol. Metab., 1993, 76 , 1489–1494.

    Gornbein J. , 'Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism ' (1993 ) 76 J. Clin. Endocrinol. Metab. : 1489 -1494.

    • Search Google Scholar
  • Brown, E. M., Fuleihan, G. E.-H., Chen, C. J. és mtsai: 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. [erratum appears in Endocrinology 1992 Aug;131(2):862]. Endocrinology, 1990, 127 , 1064–1071.

    Chen C. J. , '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 ' (1990 ) 127 Endocrinology : 1064 -1071.

    • Search Google Scholar
  • Breitwieser, G. E., Miedlich, S. U., Zhang, M.: Calcium sensing receptors as integrators of multiple metabolic signals. Cell Calcium, 2004, 35 , 209–216.

    Zhang M. , 'Calcium sensing receptors as integrators of multiple metabolic signals ' (2004 ) 35 Cell Calcium : 209 -216.

    • Search Google Scholar
  • Petrel, C., Kessler, A., Dauban, P. és mtsai: Positive and negative allosteric modulators of the Ca 2+ -sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J. Biol. Chem., 2004, 279 , 18990–18997.

    Dauban P. , 'Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain ' (2004 ) 279 J. Biol. Chem. : 18990 -18997.

    • Search Google Scholar
  • Conigrave, A. D., Quinn, S. J., Brown, E. M.: L-amino acid sensing by the extracellular Ca 2+ -sensing receptor [see comment]. Proc. Natl. Acad. Sci. U. S. A., 2000, 97 , 4814–4819.

    Brown E. M. , 'L-amino acid sensing by the extracellular Ca2+-sensing receptor [see comment] ' (2000 ) 97 Proc. Natl. Acad. Sci. U. S. A. : 4814 -4819.

    • Search Google Scholar
  • Bai, M., Quinn, S., Trivedi, S. és mtsai: Expression and characterization of inactivating and activating mutations in the human Ca 2+ o -sensing receptor. J. Biol. Chem., 1996, 271 , 19537–19545.

    Trivedi S. , 'Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor ' (1996 ) 271 J. Biol. Chem. : 19537 -19545.

    • Search Google Scholar
  • Kifor, O., Diaz, R., Butters, R. és mtsai: The Ca 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., 1997, 12 , 715–725.

    Butters R. , 'The Ca2+-sensing receptor (CaR) activates phospholipases C, A2, and D in bovine parathyroid and CaR-transfected, human embryonic kidney (HEK293) cells ' (1997 ) 12 J. Bone Miner. Res. : 715 -725.

    • Search Google Scholar
  • Muff, R., Nemeth, E. F., Haller-Brem, S. és mtsai: Regulation of hormone secretion and cytosolic Ca 2+ by extracellular Ca 2+ in parathyroid cells and C-cells: role of voltage-sensitive Ca 2+ channels. Arch. Biochem. Biophys., 1988, 265 , 128–135.

    Haller-Brem S. , 'Regulation of hormone secretion and cytosolic Ca2+ by extracellular Ca2+ in parathyroid cells and C-cells: role of voltage-sensitive Ca2+ channels ' (1988 ) 265 Arch. Biochem. Biophys. : 128 -135.

    • Search Google Scholar
  • Chang, W., Chen, T. H., Gardner, P. és mtsai: Regulation of Ca(2+)-conducting currents in parathyroid cells by extracellular Ca(2+) and channel blockers. Am. J. Physiol., 1995, 269 , E864–877.

    Gardner P. , 'Regulation of Ca(2+)-conducting currents in parathyroid cells by extracellular Ca(2+) and channel blockers ' (1995 ) 269 Am. J. Physiol. : E864 -877.

    • Search Google Scholar
  • Chen, C. J., Barnett, J. V., Congo, D. A. és mtsai: Divalent cations suppress 3’,5’-adenosine monophosphate accumulation by stimulating a pertussis toxin-sensitive guanine nucleotide-binding protein in cultured bovine parathyroid cells. Endocrinology, 1989, 124 , 233–239.

    Congo D. A. , 'Divalent cations suppress 3’,5’-adenosine monophosphate accumulation by stimulating a pertussis toxin-sensitive guanine nucleotide-binding protein in cultured bovine parathyroid cells ' (1989 ) 124 Endocrinology : 233 -239.

    • Search Google Scholar
  • Roux, P. P., Blenis, J.: ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev., 2004, 68 , 320–344.

    Blenis J. , 'ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions ' (2004 ) 68 Microbiol. Mol. Biol. Rev. : 320 -344.

    • Search Google Scholar
  • Pi, M., Oakley, R. H., Gesty-Palmer, D. és mtsai: Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization. Mol. Endocrinol., 2005, 19 , 1078–1087.

    Gesty-Palmer D. , 'Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization ' (2005 ) 19 Mol. Endocrinol. : 1078 -1087.

    • Search Google Scholar
  • Lorenz, S., Frenzel, R., Paschke, R. és mtsai: 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, 2007, 148 , 2398–2404.

    Paschke R. , '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 ' (2007 ) 148 Endocrinology : 2398 -2404.

    • Search Google Scholar
  • Watson, P. H., Hanley, D. A.: Parathyroid hormone: regulation of synthesis and secretion. Clin. Invest. Med., 1993, 16 , 58–77.

    Hanley D. A. , 'Parathyroid hormone: regulation of synthesis and secretion ' (1993 ) 16 Clin. Invest. Med. : 58 -77.

    • Search Google Scholar
  • Brown, E. M.: Calcium receptor and regulation of parathyroid hormone secretion. Rev. Endocr. Metab. Disord., 2000, 1 , 307–315.

    Brown E. M. , 'Calcium receptor and regulation of parathyroid hormone secretion ' (2000 ) 1 Rev. Endocr. Metab. Disord. : 307 -315.

    • Search Google Scholar
  • Ritter, C. S., Pande, S., Krits, I. és mtsai: Destabilization of parathyroid hormone mRNA by extracellular Ca 2+ and the calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for gene transcription. J. Mol. Endocrinol., 2008, 40 , 13–21.

    Krits I. , '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 ' (2008 ) 40 J. Mol. Endocrinol. : 13 -21.

    • Search Google Scholar
  • Nechama, M., Ben Dov, I. Z., Silver, J. és mtsai: Regulation of PTH mRNA stability by the calcimimetic R568 and the phosphorus binder lanthanum carbonate in CKD.; Am. J. Physiol. Renal. Physiol., 2009, Jan 7 (Epub ahead of print).

  • Tominaga, Y.: Mechanism of parathyroid tumourigenesis in uraemia. Nephrol. Dial. Transplant., 1999, 14 , 63–65.

    Tominaga Y. , 'Mechanism of parathyroid tumourigenesis in uraemia ' (1999 ) 14 Nephrol. Dial. Transplant. : 63 -65.

    • Search Google Scholar
  • Chen, R. A., Goodman, W. G.: Role of the calcium-sensing receptor in parathyroid gland physiology. Am. J. Physiol. Renal Physiol., 2004, 286 , F1005–1011.

    Goodman W. G. , 'Role of the calcium-sensing receptor in parathyroid gland physiology ' (2004 ) 286 Am. J. Physiol. Renal Physiol. : F1005 -1011.

    • Search Google Scholar
  • Goodman, W. G.: The flavors of vitamin D: tasting the molecular mechanisms [comment]. Kidney Int., 2004, 66 , 1286–1287.

    Goodman W. G. , 'The flavors of vitamin D: tasting the molecular mechanisms [comment] ' (2004 ) 66 Kidney Int. : 1286 -1287.

    • Search Google Scholar
  • McGehee, D. S., Aldersberg, M., Liu, K. P. és mtsai: Mechanism of extracellular Ca 2+ receptor-stimulated hormone release from sheep thyroid parafollicular cells. J. Physiol., 1997, 502 , 31–44.

    Liu K. P. , 'Mechanism of extracellular Ca2+ receptor-stimulated hormone release from sheep thyroid parafollicular cells ' (1997 ) 502 J. Physiol. : 31 -44.

    • Search Google Scholar
  • Riccardi, D., Hall, A. E., Chattopadhyay, N. és mtsai: Localization of the extracellular Ca 2+ /polyvalent cation-sensing protein in rat kidney. Am. J. Physiol., 1998, 274 , F611–622.

    Chattopadhyay N. , 'Localization of the extracellular Ca2+/polyvalent cation-sensing protein in rat kidney ' (1998 ) 274 Am. J. Physiol. : F611 -622.

    • Search Google Scholar
  • Ba, J., Brown, D., Friedman, P. A.: Calcium-sensing receptor regulation of PTH-inhibitable proximal tubule phosphate transport. Am. J. Physiol. Renal Physiol., 2003, 285 , F1233–1243.

    Friedman P. A. , 'Calcium-sensing receptor regulation of PTH-inhibitable proximal tubule phosphate transport ' (2003 ) 285 Am. J. Physiol. Renal Physiol. : F1233 -1243.

    • Search Google Scholar
  • Wang, W., Lu, M., Balazy, M. és mtsai: Phospholipase A2 is involved in mediating the effect of extracellular Ca 2+ on apical K +  channels in rat TAL. Am. J. Physiol., 1997, 273 , F421–429.

    Balazy M. , 'Phospholipase A2 is involved in mediating the effect of extracellular Ca2+ on apical K+ channels in rat TAL ' (1997 ) 273 Am. J. Physiol. : F421 -429.

    • Search Google Scholar
  • Blankenship, K. A., Williams, J. J., Lawrence, M. S. és mtsai: The calcium-sensing receptor regulates calcium absorption in MDCK cells by inhibition of PMCA. Am. J. Physiol. Renal Physiol., 2001, 280 , F815–822.

    Lawrence M. S. , 'The calcium-sensing receptor regulates calcium absorption in MDCK cells by inhibition of PMCA ' (2001 ) 280 Am. J. Physiol. Renal Physiol. : F815 -822.

    • Search Google Scholar
  • Sands, J. M., Naruse, M., Baum, M. és mtsai: Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. J. Clin. Invest., 1997, 99 , 1399–1405.

    Baum M. , 'Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct ' (1997 ) 99 J. Clin. Invest. : 1399 -1405.

    • Search Google Scholar
  • Bustamante, M., Hasler, U., Leroy, V. és mtsai: Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism. J. Am. Soc. Nephrol., 2008, 19 , 109–116.

    Leroy V. , 'Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism ' (2008 ) 19 J. Am. Soc. Nephrol. : 109 -116.

    • Search Google Scholar
  • Buchan, A. M., Squires, P. E., Ring, M. és mtsai: Mechanism of action of the calcium-sensing receptor in human antral gastrin cells [see comment]. Gastroenterology, 2001, 120 , 1128–1139.

    Ring M. , 'Mechanism of action of the calcium-sensing receptor in human antral gastrin cells [see comment] ' (2001 ) 120 Gastroenterology : 1128 -1139.

    • Search Google Scholar
  • Bevilacqua, M., Dominguez, L. J., Righini, V. és mtsai: Increased gastrin and calcitonin secretion after oral calcium or peptones administration in patients with hypercalciuria: a clue to an alteration in calcium-sensing receptor activity. J. Clin. Endocrinol. Metab., 2005, 90 , 1489–1494.

    Righini V. , 'Increased gastrin and calcitonin secretion after oral calcium or peptones administration in patients with hypercalciuria: a clue to an alteration in calcium-sensing receptor activity ' (2005 ) 90 J. Clin. Endocrinol. Metab. : 1489 -1494.

    • Search Google Scholar
  • Hebert, S. C., Cheng, S., Geibel, J.: Functions and roles of the extracellular Ca 2+ -sensing receptor in the gastrointestinal tract. Cell Calcium, 2004, 35 , 239–247.

    Geibel J. , 'Functions and roles of the extracellular Ca2+-sensing receptor in the gastrointestinal tract ' (2004 ) 35 Cell Calcium : 239 -247.

    • Search Google Scholar
  • Geibel, J., Sritharan, K., Geibel, R. és mtsai: Calcium-sensing receptor abrogates secretagogue-induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction [see comment]. Proc. Natl. Acad. Sci. U. S. A., 2006, 103 , 9390–9397.

    Geibel R. , 'Calcium-sensing receptor abrogates secretagogue-induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction [see comment] ' (2006 ) 103 Proc. Natl. Acad. Sci. U. S. A. : 9390 -9397.

    • Search Google Scholar
  • Dvorak, M. M., Riccardi, D.: Ca 2+ as an extracellular signal in bone. Cell Calcium, 2004, 35 , 249–255.

    Riccardi D. , 'Ca2+ as an extracellular signal in bone ' (2004 ) 35 Cell Calcium : 249 -255.

  • Huan, J., Martuseviciene, G., Olgaard, K. és mtsai: Calcium-sensing receptor and recovery from hypocalcaemia in thyroparathyroidectomized rats. Eur. J. Clin. Invest., 2007, 37 , 214–221.

    Olgaard K. , 'Calcium-sensing receptor and recovery from hypocalcaemia in thyroparathyroidectomized rats ' (2007 ) 37 Eur. J. Clin. Invest. : 214 -221.

    • Search Google Scholar
  • Kanatani, M., Sugimoto, T., Kanzawa, M. és mtsai: 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., 1999, 261 , 144–148.

    Kanzawa M. , 'High extracellular calcium inhibits osteoclast-like cell formation by directly acting on the calcium-sensing receptor existing in osteoclast precursor cells ' (1999 ) 261 Biochem. Biophys. Res. Commun. : 144 -148.

    • Search Google Scholar
  • Yamaguchi, T., Chattopadhyay, N., Kifor, O. és mtsai: Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca 2+ o )-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells. J. Bone Miner. Res., 1998, 13 , 1530–1538.

    Kifor O. , 'Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells ' (1998 ) 13 J. Bone Miner. Res. : 1530 -1538.

    • Search Google Scholar
  • Deyama, A., Deyama, Y., Matsumoto, A. és mtsai: A low calcium environment enhances AP-1 transcription factor-mediated gene expression in the development of osteoblastic MC3T3-E1 cells. Miner. Electrolyte Metab., 1999, 25 , 147–160.

    Matsumoto A. , 'A low calcium environment enhances AP-1 transcription factor-mediated gene expression in the development of osteoblastic MC3T3-E1 cells ' (1999 ) 25 Miner. Electrolyte Metab. : 147 -160.

    • Search Google Scholar
  • Bradbury, R. A., Cropley, J., Kifor, O. és mtsai: Localization of the extracellular Ca 2+ -sensing receptor in the human placenta. Placenta, 2002, 23 , 192–200.

    Kifor O. , 'Localization of the extracellular Ca2+-sensing receptor in the human placenta ' (2002 ) 23 Placenta : 192 -200.

    • Search Google Scholar
  • Hellman, P., Hellman, B., Juhlin, C. és mtsai: Regulation of proliferation in JEG-3 cells by a 500-kDa Ca 2+ sensor and parathyroid hormone-related protein. Arch. Biochem. Biophys., 1993, 307 , 379–385.

    Juhlin C. , 'Regulation of proliferation in JEG-3 cells by a 500-kDa Ca2+ sensor and parathyroid hormone-related protein ' (1993 ) 307 Arch. Biochem. Biophys. : 379 -385.

    • Search Google Scholar
  • Foley, T. P., Jr., Harrison, H. C., Arnaud, C. D. és mtsai: Familial benign hypercalcemia. J. Pediatr., 1972, 81 , 1060–1067.

    Arnaud C. D. , 'Familial benign hypercalcemia ' (1972 ) 81 J. Pediatr. : 1060 -1067.

  • Pollak, M. R., Brown, E. M., Chou, Y. H. és mtsai: Mutations in the human Ca 2+ -sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism [see comment]. Cell, 1993, 75 , 1297–1303.

    Chou Y. H. , 'Mutations in the human Ca2+-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism [see comment] ' (1993 ) 75 Cell : 1297 -1303.

    • Search Google Scholar
  • Gunn, I. R., Gaffney, D.: Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. Ann. Clin. Biochem., 2004, 41 , 441–458.

    Gaffney D. , 'Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review ' (2004 ) 41 Ann. Clin. Biochem. : 441 -458.

    • Search Google Scholar
  • Hinnie, J., Bell, E., McKillop, E. és mtsai: The prevalence of familial hypocalciuric hypercalcemia [see comment]. Calcif. Tissue Int., 2001, 68 , 216–218.

    McKillop E. , 'The prevalence of familial hypocalciuric hypercalcemia [see comment]. Calcif ' (2001 ) 68 Tissue Int. : 216 -218.

    • Search Google Scholar
  • Bilezikian, J. P., Potts, J. T., Jr., Fuleihan, G. E.-H. és mtsai: Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. J. Clin. Endocrinol. Metab., 2002, 87 , 5353–5361.

    Fuleihan G. E.-H. , 'Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century ' (2002 ) 87 J. Clin. Endocrinol. Metab. : 5353 -5361.

    • Search Google Scholar
  • Christensen, S. E., Nissen, P. H., Vestergaard, P. és mtsai: Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow-up study on methods. Clin. Endocrinol. (Oxf), 2008, 69 , 713–720.

    Vestergaard P. , 'Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow-up study on methods ' (2008 ) 69 Clin. Endocrinol. (Oxf) : 713 -720.

    • Search Google Scholar
  • Egbuna, O. I., Brown, E. M.: Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations. Best Pract. Res. Clin. Rheumatol., 2008, 22 , 129–148.

    Brown E. M. , 'Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations ' (2008 ) 22 Best Pract. Res. Clin. Rheumatol. : 129 -148.

    • Search Google Scholar
  • Lloyd, S. E., Pannett, A. A., Dixon, P. H. és mtsai: Localization of familial benign hypercalcemia, Oklahoma variant (FBHOk), to chromosome 19q13. Am. J. Hum. Genet., 1999, 64 , 189–195.

    Dixon P. H. , 'Localization of familial benign hypercalcemia, Oklahoma variant (FBHOk), to chromosome 19q13 ' (1999 ) 64 Am. J. Hum. Genet. : 189 -195.

    • Search Google Scholar
  • Rus, R., Haag, C., Bumke-Vogt, C. és mtsai: Novel inactivating mutations of the calcium-sensing receptor: the calcimimetic NPS R-568 improves signal transduction of mutant receptors. J. Clin. Endocrinol. Metab., 2008, 93 , 4797–4803.

    Bumke-Vogt C. , 'Novel inactivating mutations of the calcium-sensing receptor: the calcimimetic NPS R-568 improves signal transduction of mutant receptors ' (2008 ) 93 J. Clin. Endocrinol. Metab. : 4797 -4803.

    • Search Google Scholar
  • Huang, Y., Breitwieser, G. E.: Rescue of calcium-sensing receptor mutants by allosteric modulators reveals a conformational checkpoint in receptor biogenesis. J. Biol. Chem., 2007, 282 , 9517–9525.

    Breitwieser G. E. , 'Rescue of calcium-sensing receptor mutants by allosteric modulators reveals a conformational checkpoint in receptor biogenesis ' (2007 ) 282 J. Biol. Chem. : 9517 -9525.

    • Search Google Scholar
  • Marx, S. J., Fraser, D., Rapoport, A.: Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes. Am. J. Med., 1985, 78 , 15–22.

    Rapoport A. , 'Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes ' (1985 ) 78 Am. J. Med. : 15 -22.

    • Search Google Scholar
  • Pearce, S. H., Trump, D., Wooding, C. és mtsai: Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism. J. Clin. Invest., 1995, 96 , 2683–2692.

    Wooding C. , 'Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism ' (1995 ) 96 J. Clin. Invest. : 2683 -2692.

    • Search Google Scholar
  • Brown, E. M.: Editorial: mutant extracellular calcium-sensing receptors and severity of disease. J. Clin. Endocrinol. Metab., 2005, 90 , 1246–1248.

    Brown E. M. , 'Editorial: mutant extracellular calcium-sensing receptors and severity of disease ' (2005 ) 90 J. Clin. Endocrinol. Metab. : 1246 -1248.

    • Search Google Scholar
  • Pallais, J. C., Kifor, O., Chen, Y.-B. és mtsai: Acquired hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor [see comment]. N. Engl. J. Med., 2004, 351 , 362–369.

    Chen Y.-B. , 'Acquired hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor [see comment] ' (2004 ) 351 N. Engl. J. Med. : 362 -369.

    • Search Google Scholar
  • Arnold, A., Shattuck, T. M., Mallya, S. M. és mtsai: Molecular pathogenesis of primary hyperparathyroidism. J. Bone Miner. Res., 2002, 17 , N30–36.

    Mallya S. M. , 'Molecular pathogenesis of primary hyperparathyroidism ' (2002 ) 17 J. Bone Miner. Res. : N30 -36.

    • Search Google Scholar
  • Brown, E. M.: The pathophysiology of primary hyperparathyroidism. J. Bone Miner. Res., 2002, 17 , N24–29.

    Brown E. M. , 'The pathophysiology of primary hyperparathyroidism ' (2002 ) 17 J. Bone Miner. Res. : N24 -29.

    • Search Google Scholar
  • Corbetta, S., Mantovani, G., Lania, A. és mtsai: Calcium-sensing receptor expression and signalling in human parathyroid adenomas and primary hyperplasia. Clin. Endocrinol. (Oxf), 2000, 52 , 339–348.

    Lania A. , 'Calcium-sensing receptor expression and signalling in human parathyroid adenomas and primary hyperplasia ' (2000 ) 52 Clin. Endocrinol. (Oxf) : 339 -348.

    • Search Google Scholar
  • Fukuda, N., Tanaka, H., Tominaga, Y. és mtsai: Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J. Clin. Invest., 1993, 92 , 1436–1443.

    Tominaga Y. , 'Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients ' (1993 ) 92 J. Clin. Invest. : 1436 -1443.

    • Search Google Scholar
  • Kifor, O., Moore, F. D., Jr., Wang, P. és mtsai: Reduced immunostaining for the extracellular Ca 2+ -sensing receptor in primary and uremic secondary hyperparathyroidism. J. Clin. Endocrinol. Metab., 1996, 81 , 1598–1606.

    Wang P. , 'Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism ' (1996 ) 81 J. Clin. Endocrinol. Metab. : 1598 -1606.

    • Search Google Scholar
  • Yano, S., Sugimoto, T., Tsukamoto, T. és mtsai: Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism. Kidney Int., 2000, 58 , 1980–1986.

    Tsukamoto T. , 'Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism ' (2000 ) 58 Kidney Int. : 1980 -1986.

    • Search Google Scholar
  • Scillitani, A., Guarnieri, V., De Geronimo, S. és mtsai: Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor. J. Clin. Endocrinol. Metab., 2004, 89 , 5634–5638.

    Geronimo S. , 'Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor ' (2004 ) 89 J. Clin. Endocrinol. Metab. : 5634 -5638.

    • Search Google Scholar
  • Scillitani, A., Guarnieri, V., Battista, C. és mtsai: Primary hyperparathyroidism and the presence of kidney stones are associated with different haplotypes of the calcium-sensing receptor. J. Clin. Endocrinol. Metab., 2007, 92 , 277–283.

    Battista C. , 'Primary hyperparathyroidism and the presence of kidney stones are associated with different haplotypes of the calcium-sensing receptor ' (2007 ) 92 J. Clin. Endocrinol. Metab. : 277 -283.

    • Search Google Scholar
  • Brown, E. M.: Clinical lessons from the calcium-sensing receptor. Nat. Clin. Pract. Endocrinol. Metab., 2007, 3 , 122–133.

    Brown E. M. , 'Clinical lessons from the calcium-sensing receptor ' (2007 ) 3 Nat. Clin. Pract. Endocrinol. Metab. : 122 -133.

    • Search Google Scholar
  • Mayer, A., Ploix, C., Orgiazzi, J. és mtsai: Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism. J. Clin. Endocrinol. Metab., 2004, 89 , 4484–4488.

    Orgiazzi J. , 'Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism ' (2004 ) 89 J. Clin. Endocrinol. Metab. : 4484 -4488.

    • Search Google Scholar