Behind the curtain: Cellular mechanisms for allosteric modulation of calcium-sensing receptors

British Journal of Pharmacology

Volumn 165, Issue 6, 2012, Pages 1670-1677

  Cavanaugh, Alice ^a   Huang, Ying ^b   Breitwieser, Gerda E ^a  

^a WEIS CENTER FOR RESEARCH   (United States)

^b ROYAL VICTORIA HOSPITAL   (Canada)

Author keywords

allosteric modulation; biosynthesis; calcilytic; calcimimetic; calcium sensing receptor; NPS 2143; NPS R 568; pharmacologic chaperone

Indexed keywords

1 (3 METHOXYPHENYL) N (3 PHENYLPROPYL)ETHYLAMINE; 2 CHLORO 6 [3 [1,1 DIMETHYL 2 (2 NAPHTHYL)ETHYLAMINO] 2 HYDROXYPROPOXY]BENZONITRILE; 4 AMINOBUTYRIC ACID B RECEPTOR; BETA ARRESTIN; CALCILYTIC AGENT; CALCIMIMETIC AGENT; CALCIUM SENSING RECEPTOR; CINACALCET; G PROTEIN COUPLED RECEPTOR; TECALCET; UNCLASSIFIED DRUG;

ALLOSTERISM; CALCIUM HOMEOSTASIS; CELL MEMBRANE; DRUG MECHANISM; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM STRESS; GAIN OF FUNCTION MUTATION; HUMAN; HYDROPHOBICITY; IMMUNOMODULATION; NONHUMAN; OSCILLATION; OSTEOPOROSIS; PARATHYROID CARCINOMA; PARATHYROID HORMONE RELEASE; PRIMARY HYPERPARATHYROIDISM; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STABILITY; PROTEIN SYNTHESIS; REVIEW; SIGNAL TRANSDUCTION; TRANSLATION REGULATION;

ANIMALS; BINDING SITES; CELL MEMBRANE; DRUG DESIGN; HUMANS; RECEPTORS, CALCIUM-SENSING; SIGNAL TRANSDUCTION;

EID: 84863115494     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01403.x     Document Type: Review

References (77)

1. Arey BJ, Seethala R, Ma Z, Fura A, Morin J, Swartz J, et al,. (2005). A novel calcium-sensing receptor antagonist transiently stimulates parathyroid hormone secretion in vivo. Endocrinol 146: 2015-2022.
2. Bernier V, Bichet DG, Bouvier M, (2004). Pharmacological chaperone action on G-protein-coupled receptors. Curr Opin Pharmacol 4: 528-533.
3. Brauner-Osborne H, Wellendorph P, Jensen AA, (2007). Structure, pharmacology and therapeutic prospects of family C G-protein coupled receptors. Curr Drug Targets 8: 169-184.
4. Broadhead GK, Mun H, Avlani VA, Jourdon O, Church WB, Christopoulos A, et al,. (2011). Allosteric modulation of calcium-sensing receptor by Î-glutamyl peptides. Inhibition of PTH secretion, suppression of intracellular cAMP levels and a common mechanism of action with L-amino acids. J Biol Chem 286: 8786-8797.
5. Brown EM, (2009). Anti-parathyroid and anti-calcium sensing receptor antibodies in autoimmuno hypoparathyroidism. Endocrinol Metab Clin North Am 38: 437-445.
6. Brown EM, (2010). Clinical utility of calcimimetics targeting the extracellular calcium-sensing receptor (CaSR). Biochem Pharmacol 80: 297-307.
7. Brown EM, MacLeod RJ, (2001). Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81: 239-297.
8. Bu L, Michino M, Wolf RM, Brooks CL 3rd, (2008). Improved model building and assessment of the calcium-sensing receptor transmembrane domain. Proteins 7: 215-226.
9. 2+ with the allosteric site of muscarinic M2 receptors. Naunyn Schmiedebergs Arch Pharmacol 357: 363-370.
10. Casero RA Jr, Marton LJ, (2007). Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov 6: 373-390.
11. Cavanaugh A, McKenna J, Stepanchick A, Breitwieser GE, (2010). Calcium-sensing receptor biosynthesis includes a contranslational checkpoint and endoplasmic reticulum retention. J Biol Chem 285: 19854-19864.
12. Chakravarthi S, Jessop CE, Bulleid NJ, (2006). The role of glutathione in disulfide bond formation and endoplasmic-reticulum-generated oxidative stress. EMBO Rep 7: 271-275.
13. Coleman SK, Moykkynen T, Jouppila A, Koskelainen S, Rivera C, Korpi ER, et al,. (2009). Agonist occupancy is essential for forward trafficking of AMPA receptors. J Neurosci 29: 303-312.
14. Conigrave A, Brown EM, (2006). Taste Receptors in the Gastrointestinal Tract. II. L-Amino acid sensing by calcium-sensing receptors: implications for GI physiology. Am J Physiol Gastrointest Liver Physiol 291: G753-G761.
15. Conigrave AD, Brown EM, Rizzoli R, (2008). Dietary protein and bone health: roles of amino acid-sensing receptors in the control of calcium metabolism and bone homeostasis. Annu Rev Nutr 28: 131-155.
16. Conn PM, Ulloa-Aguirre A, (2009). Trafficking of G-protein-coupled receptors to the plasma membrane: insights for pharmacochaperone drugs. Trends Endocrinol Metab 21: 190-197.
17. Corbetta S, Mantovani G, Lania A, Borgato S, Vicentini L, Beretta S, et al,. (2000). Calcium-sensing receptor expression and signalling in human parathyroid adenomas and primary hyperplasia. Clin Endocrinol 52: 339-348.
18. D'Angelo JA, Dehlink E, Platzer B, Dwyer P, Circu ML, Garay J, et al,. (2010). The cystine/glutamate antiporter regulates dendritic cell differentiation and antigen presentation. J Immunol 185: 3217-3226.
19. DeWire SM, Kim J, Whalen EJ, Ahn S, Chen M, Lefkowitz RJ, (2008). β-Arrestin-mediated signaling regulates protein synthesis. J Biol Chem 283: 10611-10620.
20. Farrell A, Morgan DO, (2000). Cdc37 promotes the stability of protein kinases Cdc28 and Cak1. Mol Cell Biol 20: 749-754.
21. Feng J, Petersen CD, Coy DH, Jiang JK, Thomas CJ, Pollak MR, et al,. (2010). Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion. Proc Natl Acad Sci U S A 107: 17791-17796.
22. Gowen M, Stroup GB, Dodds RA, James IE, Votta BJ, Smith BR, et al,. (2000). Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest 105: 1595-1604.
23. Han L, Xu C, Guo Y, Li H, Jiang C, Zhao Y, (2009). Polyamine metabolism in rat myocardial ischemia-reperfusion injury. Int J Cardiol 132: 142-144.
24. Harrington PE, Fotsch C, (2007). Calcium sensing receptor activators: calcimimetics. Curr Med Chem 14: 3027-3034.
25. 2+ receptor/metabotropic glutamate chimeric receptors. Endocrinol 141: 4156-4163.
26. Hebert SC, (2006). Therapeutic use of calcimimetics. Annu Rev Med 57: 349-364.
27. Hu J, Wang SZ, Forray C, el-Fakahany EE, (1992). Complex allosteric modulation of cardiac muscarinic receptors by protamine: potential model for putative endogenous ligands. Mol Pharmacol 42: 311-321.
28. 2+ receptor cysteine-rich domain. Analysis of function of mutant and chimeric receptors. J Biol Chem 275: 16382-16389.
29. Huang Y, Breitwieser GE, (2007). Rescue of calcium-sensing receptor mutants by allosteric modulators reveals a conformational checkpoint in receptor biogenesis. J Biol Chem 282: 9517-9525.
30. Janovick JA, Patny A, Mosley R, Goulet MT, Altman MK, Rush TS, et al,. (2009). Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: the GnRH receptor. Mol Endocrinol 23: 157-168.
31. Kawata T, Nagano N, Obi M, Miyata S, Koyama C, Kobayashi N, et al,. (2008). Cinacalcet suppresses calcification of the aorta and heart in uremic rats. Kidney Int 74: 1270-1277.
32. Kenny AV, Cousins SL, Pinho L, Stephenson FA, (2009). The integrity of the glycine co-agonist binding site of N-methyl-D-aspartate receptors is a functional quality control checkpoint for cell surface delivery. J Biol Chem 284: 324-333.
33. Keov P, Sexton PM, Christopoulos A, (2011). Allosteric modulation of G protein-coupled receptors: a pharmacological perspective. Neuropharmacology 60: 24-35.
34. Lane JR, Beukers MW, Mulder-Krieger T, Ijzerman AP, (2009). The endocannabinoid 2-arachidonylglycerol is a negative allosteric modulator of the human A3 adenosine receptor. Biochem Pharmacol 79: 48-56.
35. Letz S, Rus R, Haag C, Dorr H-G, Schnabel D, Mohlig M, 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-E233.
36. Lu JY, Yang Y, Gnacadja G, Christopoulos A, Reagan JD, (2009). Effect of the calcimimetic R-568 [3-(2-chlorophenyl)-N-((1R)-1-(3-methoxyphenyl)ethyl)-1- propanamine) on correcting inactivating mutations in the human calcium-sensing receptor. J Pharmacol Exp Thera 331: 775-786.
37. Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, et al,. (2009). Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. J Clin Endocrinol Metab 94: 2766-2772.
38. Marie PJ, (2010). The calcium-sensing receptor in bone cells: a potential therapeutic target in osteoporosis. Bone 46: 571-576.
39. 2+ signaling and calcium binding chaperones of the endoplasmic reticulum. Cell Calcium 32: 269-278.
40. Miedlich SU, Gama L, Seuwen K, Wolf RM, Breitwieser GE, (2004). Homology modeling of the transmembrane domain of the human calcium sensing receptor and localization of an allosteric binding site. J Biol Chem 279: 7254-7263.
41. Morello J-P, Salahpour A, Laperriere A, Bernier V, Arthus M-F, Lonergan M, et al,. (2000). Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 105: 887-895.
42. 2+-sensing receptor is required for L-amino acid sensing. J Biol Chem 279: 51739-51744.
43. 2+-sensing receptor's venus flytrap domain that selectively disables L-amino acid sensing. J Biol Chem 280: 29067-29072.
44. Musnier A, Blanchot B, Reiter E, Crepieux P, (2010). GPCR signalling to the translation machinery. Cellular Signalling 22: 707-716.
45. Nagano N, (2006). Pharmacological and clinical properties of calcimimetics: calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism. Pharmacol & Thera 109: 339-365.
46. Nemeth EF, Steffey ME, Hammerland LG, Hung BCP, Van Wagenen BC, DelMar EG, et al,. (1998). Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci U S A 95: 4040-4045.
47. 2+ receptor antagonists that stimulate secretion of parathyroid hormone. J Pharmacol Exp Ther 299: 323-331.
48. Oh WJ, Wu CC, Kim SJ, Facchinetti V, Julien LA, Finlan M, et al,. (2010). mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide. EMBO J 29: 3939-3951.
49. Ohsu T, Amino Y, Nagasaki H, Yamanaka T, Takeshita S, Hatanaka T, et al,. (2010). Involvement of the calcium-sensing receptor in human taste perception. J Biol Chem 285: 1016-1022.
50. Padhi D, Harris R, (2009). Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet 48: 303-311.
51. Penn AC, Williams SR, Greger IH, (2008). Gating motions underlie AMPA receptor secretion from the endoplasmic reticulum. EMBO J 27: 2056-2068.
52. Pereira ER, Liao N, Neale GA, Hendershot LM, (2010). Transcriptional and post-transcriptional regulation of proangiogenic factors by the unfolded protein response. Plos One 5: e12521.
53. Petaja-Repo UE, Hogue M, Bhalla S, Laperriere A, Morello JP, Bouvier M, (2002). Ligands act as pharmacological chaperones and increase the efficiency of delta opioid receptor maturation. EMBO J 21: 1628-1637.
54. Pietrogrande L, (2010). Update on the efficacy, safety, and adherence to treatment of full length parathyroid hormone, PTH(1-84), in the treatment of postmenopausal osteoporosis. Int J Women's Health 9: 193-203.
55. Proud CG, (2007). Signalling to translation: how signal transduction pathways control the protein synthetic machinery. Biochem J 403: 217-234.
56. 2+-sensing receptor: a target for polyamines. Am J Physiol Cell Physiol 273: C1315-C1323.
57. 2+ receptor. J Biol Chem 277: 18908-18913.
58. Reh CMS, Hendy GN, Cole DEC, Jeandron DD, (2011). Neonatal hyperparathyroidism with a heterozygous calcium-sensing receptor (CASR) R185Q mutation: clinical benefit from cinacalcet. J Clin Endocrin Metab 96: E707-E712.
59. 2+-sensing receptor are mediated by a phospholipase C/inositol 1,4,5-trisphosphate-independent pathway that requires G12, Rho, filamin-A, and the actin cytoskeleton. J Biol Chem 280: 22875-22882.
60. Robben JG, Sze M, Knoers NVAM, Deen PMT, (2007). Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 292: F253-F260.
61. Rothe H, Mayer G, (2006). Clinical importance of calcium-sensing receptor gene polymorphism Arg990Gly in the age of calcimimetic therapy. Curr Pharmacogenomics 4: 153-156.
62. Rus R, Haag C, Bumke-Vogt C, Bahr V, Mayr B, Mohlig M, 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.
63. Saidak Z, Brazier M, Kamel S, Mentaverri R, (2009a). Agonists and allosteric modulators of the calcium-sensing receptor and their therapeutic applications. Mol Pharmacol 76: 1131-1144.
64. Saidak Z, Mentaverri R, Brown EM, (2009b). The role of the calcium-sensing receptor in the development and progression of cancer. Endocr Rev 30: 178-195.
65. Smith NJ, Milligan G, (2010). Allostery at G protein-coupled receptor homo- and heteromers: uncharted pharmacological landscapes. Pharmacol Rev 62: 701-725.
66. Sun J, Murphy E, (2010). Calcium-sensing receptor: a sensor and mediator of ischemic preconditioning in the heart. Am J Physiol Heart Circ Physiol 299: H1309-H1317.
67. Tfelt-Hansen J, Brown EM, (2005). The calcium-sensing receptor in normal physiology and pathophysiology: a review. Crit Rev Clin Lab Sci 42: 35-70.
68. Timmers HJ, Karperien M, Hamdy NA, de Boer H, Hermus AR, (2006). Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo inactivating mutation of the calcium-sensing receptor. J Intern Med 260: 177-182.
69. Torres PU, (2006). Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease. J Ren Nutr 16: 254-258.
70. Urwyler S, (2011). Allosteric modulation of Family C G protein-coupled receptors: from molecular insights to therapeutic perspectives. Pharmacol Rev 63: 59-126.
71. Wellendorph P, Johansen LD, Brauner-Osborne H, (2009). Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients. Mol Pharmacol 76: 453-465.
72. White E, McKenna J, Cavanaugh A, Breitwieser GE, (2009). Pharmacochaperone-mediated rescue of calcium-sensing receptor loss-of-function mutants. Mol Endocrinol 23: 1115-1123.
73. Widler L, Altmann E, Beerli R, Breitenstein W, Bouhelal R, Buhl T, et al,. (2010). 1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: a novel series of potent calcium-sensing receptor antagonists. J Med Chem 53: 2250-2263.
74. Wootten D, Simms J, Koole C, Woodman OL, Summers RJ, Chroistopoulos A, et al,. (2011). Modulation of the glucagon-like peptide-1 receptor signalling by naturally occurring and synthetic flavonoids. J Pharmacol Exp Ther 336: 540-550.
75. Wuller S, Wiesner B, Loffler A, Furkert J, Krause G, Hermosilla R, et al,. (2004). Pharmacochaperones post-translationally enhance cell surface expression by increasing conformation stability of wild-type and mutant vasopressin V2 receptors. J Biol Chem 279: 47254-47263.
76. 2+-sensing receptor. Am J Physiol Cell Physiol 282: C1414-C1422.
77. Yun FH, Wong BY, Chase M, Shuen AY, Canaff L, Thongthai K, et al,. (2007). Genetic variation at the calcium-sensing receptor (CASR) locus: implication for clinical molecular diagnostics. Clin Biochem 40: 551-561.