Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome type 5 and autosomal dominant hypocalcemia

PLoS ONE

Volumn 9, Issue 12, 2014, Pages

  Letz, Saskia ^a   Haag, Christine ^b   Schulze, Egbert ^b   Frank Raue, Karin ^b   Raue, Friedhelm ^b   Hofner, Benjamin ^c   Mayr, Bernhard ^a   Schöfl, Christof ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b Endocrine Practice   (Germany)

^c UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOALCOHOL; ATF 936; AXT 914; CALCIUM SENSING RECEPTOR; NPS 2143; QUINAZOLINONE DERIVATIVE; UNCLASSIFIED DRUG; ATF936; AXT914; CALCIUM; N-(2-HYDROXY-3-(2-CYANO-3-CHLOROPHENOXY)PROPYL)-1,1-DIMETHYL-2-(2-NEPHTHYL)ETHYLAMINE; NAPHTHALENE DERIVATIVE;

ARTICLE; AUTOSOMAL DOMINANT HYPOCALCEMIA; BARTTER SYNDROME; BARTTER SYNDROME TYPE 5; CALCIUM SIGNALING; CONTROLLED STUDY; DRUG MECHANISM; GENE MUTATION; HETEROZYGOSITY; HUMAN; HUMAN CELL; HYPOCALCEMIA; MUTANT; PROTEIN EXPRESSION; DRUG EFFECTS; GENETICS; HEK293 CELL LINE; HYPERCALCIURIA; HYPOPARATHYROIDISM; METABOLISM; MUTATION;

BARTTER SYNDROME; CALCIUM; CALCIUM SIGNALING; HEK293 CELLS; HUMANS; HYPERCALCIURIA; HYPOCALCEMIA; HYPOPARATHYROIDISM; MUTATION; NAPHTHALENES; QUINAZOLINONES; RECEPTORS, CALCIUM-SENSING;

EID: 84918808005     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0115178     Document Type: Article

References (36)

1. Riccardi D, Brown EM (2010) Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol 298: F485-499.
2. Hu J, Spiegel AM (2007) Structure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators. J Cell Mol Med 11: 908-922.
3. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, et al. (1993) Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 366: 575-580.
4. Hofer AM, Brown EM (2003) Extracellular calcium sensing and signalling. Nat Rev Mol Cell Biol 4: 530-538.
5. Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, et al. (2013) Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia. N Engl J Med 368: 2476-2486.
6. Egbuna OI, Brown EM (2008) Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations. Best Pract Res Clin Rheumatol 22: 129-148.
7. Pollak MR, Brown EM, Estep HL, McLaine PN, Kifor O, et al. (1994) Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. Nat Genet 8: 303-307.
8. Raue F, Pichl J, Dörr HG, Schnabel D, Heidemann P, et al. (2011) Activating mutations in the calcium-sensing receptor: genetic and clinical spectrum in 25 patients with autosomal dominant hypocalcaemia - a German survey. Clin Endocrinol (Oxf) 75: 760-765.
9. Sayer JA, Pearce SH (2003) Extracellular calcium-sensing receptor dysfunction is associated with two new phenotypes. Clin Endocrinol (Oxf) 59: 419-421.
10. Theman TA, Collins MT, Dempster DW, Zhou H, Reynolds JC, et al. (2009) PTH(1-34) replacement therapy in a child with hypoparathyroidism caused by a sporadic calcium receptor mutation. J Bone Miner Res 24: 964-973.
11. Gonzales MC, Lieb DC, Richardson DW, O'Brian JT, Aloi JA, et al. (2013) Recombinant human parathyroid hormone therapy (1-34) in an adult patient with a gain-of-function mutation in the calcium-sensing receptor-a case report. Endocr Pract 19: e24-28.
12. Hu J, Mora S, Weber G, Zamproni I, Proverbio MC, et al. (2004) Autosomal dominant hypocalcemia in monozygotic twins caused by a de novo germline mutation near the amino-terminus of the human calcium receptor. J Bone Miner Res 19: 578-586.
13. Vargas-Poussou R, Huang C, Hulin P, Houillier P, Jeunemaitre X, et al. (2002) Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome. J Am Soc Nephrol 13: 2259-2266.
14. Watanabe S, Fukumoto S, Chang H, Takeuchi Y, Hasegawa Y, et al. (2002) Association between activating mutations of calcium-sensing receptor and Bartter's syndrome. Lancet 360: 692-694.
15. Vezzoli G, Arcidiacono T, Paloschi V, Terranegra A, Biasion R, et al. (2006) Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome. J Nephrol 19: 525-528.
16. Zhao XM, Hauache O, Goldsmith PK, Collins R, Spiegel AM (1999) A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor. FEBS Lett 448: 180-184.
17. Gowen M, Stroup GB, Dodds RA, James IE, Votta BJ, et al. (2000) Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest 105: 1595-1604.
18. Nemeth EF, Delmar EG, Heaton WL, Miller MA, Lambert LD, et al. (2001) Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone. J Pharmacol Exp Ther 299: 323-331.
19. Widler L (2011) Calcilytics: antagonists of the calcium-sensing receptor for the treatment of osteoporosis. Future Med Chem 3: 535-547.
20. Letz S, Rus R, Haag C, Dörr HG, Schnabel D, et al. (2010) Novel activating mutations of the calcium-sensing receptor: the calcilytic NPS-2143 mitigates excessive signal transduction of mutant receptors. J Clin Endocrinol Metab 95: E229-233.
21. Rus R, Haag C, Bumke-Vogt C, Bähr V, Mayr B, et al. (2008) Novel inactivating mutations of the calcium-sensing receptor: the calcimimetic NPS R-568 improves signal transduction of mutant receptors. J Clin Endocrinol Metab 93: 4797-4803.
22. Szczawinska D, Schnabel D, Letz S, Schöfl C (2014) A homozygous CaSR mutation causing a FHH phenotype completely masked by vitamin D deficiency presenting as rickets. J Clin Endocrinol Metab: epub ahead of print.
23. Motulsky H, Christopoulos A (2004) Fitting Models to Biological Data Using Linear and Nonlinear Regression: A Practical Guide to Curve Fitting: Oxford University Press, USA.
24. Bates DM, Watts DG (1998) Nonlinear Regression Analysis and Its Applications. New York: Wiley.
25. Leach K, Wen A, Davey AE, Sexton PM, Conigrave AD, et al. (2012) Identification of molecular phenotypes and biased signaling induced by naturally occurring mutations of the human calcium-sensing receptor. Endocrinology 153: 4304-4316.
26. D'Souza-Li L (2006) The calcium-sensing receptor and related diseases. Arq Bras Endocrinol Metabol 50: 628-639.
27. Magno AL, Ward BK, Ratajczak T (2011) The calcium-sensing receptor: a molecular perspective. Endocr Rev 32: 3-30.
28. Lienhardt A, Bai M, Lagarde JP, Rigaud M, Zhang Z, et al. (2001) Activating mutations of the calcium-sensing receptor: management of hypocalcemia. J Clin Endocrinol Metab 86: 5313-5323.
29. John MR, Harfst E, Loeffler J, Belleli R, Mason J, et al. (2014) AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women. Bone 64C: 204-210.
30. Caltabiano S, Desjardins J, Hossain M, Kurtinecz M, Fitzpatrick L (2009) Characterization of the effect of ronacaleret, a calcium-sensing receptor antagonist, on renal calcium excretion. J Bone Miner Res 24 (Suppl 1).
31. Fitzpatrick L, Dabrowski C, Cicconetti G, Papapoulos S, Bone H, et al. (2009) Ronacaleret, a calcium-sensing receptor antagonist: results of a 1 year double-blind, placebo-controlled, dose-ranging phase II study. J Bone Miner Res 24 (Suppl 1).
32. Macleod RJ (2013) CaSR function in the intestine: Hormone secretion, electrolyte absorption and secretion, paracrine non-canonical Wnt signaling and colonic crypt cell proliferation. Best Pract Res Clin Endocrinol Metab 27: 385-402.
33. Liu XL, Lu YS, Gao JY, Marshall C, Xiao M, et al. (2013) Calcium sensing receptor absence delays postnatal brain development via direct and indirect mechanisms. Mol Neurobiol 48: 590-600.
34. Lia-Baldini AS, Magdelaine C, Nizou A, Airault C, Salles JP, et al. (2013) Two novel mutations of the calcium-sensing receptor gene affecting the same amino acid position lead to opposite phenotypes and reveal the importance of p.N802 on receptor activity. Eur J Endocrinol 168: K27-34.
35. Hu J, McLarnon SJ, Mora S, Jiang J, Thomas C, et al. (2005) A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+ . J Biol Chem 280: 5113-5120.
36. Park SY, Mun HC, Eom YS, Baek HL, Jung TS, et al. (2013) Identification and characterization of D410E, a novel mutation in the loop 3 domain of CASR, in autosomal dominant hypocalcemia and a therapeutic approach using a novel calcilytic, AXT914. Clin Endocrinol (Oxf) 78: 687-693.