'Biasing' the parathyroid hormone receptor: A novel anabolic approach to increasing bone mass?

British Journal of Pharmacology

Volumn 164, Issue 1, 2011, Pages 59-67

  Gesty Palmer, Diane ^a,b   Luttrell, Louis M ^c,d  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b DURHAM VA MEDICAL CENTER   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^d RALPH H JOHNSON VA MEDICAL CENTER   (United States)

Author keywords

arrestin; biased agonism; bone metabolism; functional selectivity; G protein coupled receptor (GPCR); GPCR signalling; osteoporosis; parathyroid hormone (PTH); type I parathyroid hormone receptor (PTH1R)

Indexed keywords

AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR AGONIST; G PROTEIN COUPLED RECEPTOR BLOCKING AGENT; PARATHYROID HORMONE; PARATHYROID HORMONE DERIVATIVE; PARATHYROID HORMONE RECEPTOR; PARATHYROID HORMONE RECEPTOR 1; PARATHYROID HORMONE RECEPTOR 1 AGONIST; PARATHYROID HORMONE RECEPTOR AGONIST; PARATHYROID HORMONE[1-31]; PARATHYROID HORMONE[1-34]; PARATHYROID HORMONE[28-42]; PARATHYROID HORMONE[28-48]; PARATHYROID HORMONE[3-34]; RECEPTOR BLOCKING AGENT; RETINA S ANTIGEN; SELECTIVE ESTROGEN RECEPTOR MODULATOR; UNCLASSIFIED DRUG;

BIOSYNTHESIS; BONE MASS; BONE METABOLISM; BONE TURNOVER; CALCIUM METABOLISM; CATABOLISM; CELL ACTIVATION; CELL MEMBRANE TRANSPORT; DRUG DESIGN; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DRUG SYNTHESIS; HORMONE ACTION; HUMAN; HYPERCALCEMIA; HYPERCALCIURIA; IN VIVO STUDY; METABOLIC BONE DISEASE; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; OSTEOPOROSIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; BONE AND BONES; HUMANS; LIGANDS; OSTEOGENESIS; OSTEOPOROSIS; RECEPTOR, PARATHYROID HORMONE, TYPE 1;

EID: 79961236811     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01450.x     Document Type: Review

References (66)

1. Abou-Samra AB, Juppner H, Force T, Freeman MW, Kong XF, Schipani E, et al,. (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 trisphosphates and increases intracellular free calcium. Proc Natl Acad Sci U S A 89: 2732-2736.
2. Angers S, Salahpour A, Bouvier M, (2002). Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. Ann Rev Pharmacol Toxicol 42: 409-435. (Pubitemid 34160532)
3. Azarani A, Goltzman D, Orlowski J, (1996). Structurally Diverse N-terminal Peptides of Parathyroid Hormone (PTH) and PTH-related Peptide (PTHRP) Inhibit the Na+/H+ Exchanger NHE3 Isoform by Binding to the PTH/PTHRP Receptor Type I and Activating Distinct Signaling Pathways. J Biol Chem 271: 14931-14936.
4. Azzi M, Charest PG, Angers S, Rousseau G, Kohout T, Bouvier M, et al,. (2003). Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors. Proc Natl Acad Sci U S A 100: 11406-11411. (Pubitemid 37205948)
5. Bisello A, Chorev M, Rosenblatt M, Monticelli L, Mierke DF, Ferrari SL, (2002). Selective ligand-induced stabilization of active and desensitized parathyroid hormone type 1 receptor conformations. J Biol Chem 277: 38524-38530. (Pubitemid 35154711)
6. Bisello A, Manen D, Pierroz DD, Usdin TB, Rizzoli R, Ferrari SL, (2004). Agonist-Specific Regulation of Parathyroid Hormone (PTH) Receptor Type 2 Activity: structural and functional analysis of PTH- and Tuberoinfundibular Peptide (TIP) 39-stimulated desensitization and internalization. Mol Endocrinol 18: 1486-1498. (Pubitemid 38692185)
7. Bockaert J, Marin P, Dumuis A, Fagni L, (2003). The 'magic tail' of G protein-coupled receptors: an anchorage for functional protein networks. FEBS Lett 546: 65-72. (Pubitemid 36782283)
8. Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT, (1999). Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science 286: 2495-2498.
9. Bouxsein ML, Pierroz DD, Glatt V, Goddard DS, Cavat F, Rizzoli R, et al,. (2005). Beta-arrestin2 regulates the differential response of cortical and trabecular bone to intermittent PTH in female mice. J Bone Mineral Res 20: 635-643. (Pubitemid 40393072)
10. Brady AE, Limbird LE, (2002). G protein-coupled receptor interacting proteins: emerging roles in localization and signal transduction. Cell Signal 14: 297-309. (Pubitemid 34164685)
11. Bringhurst FR, Juppner H, Guo J, Urena P, Potts JT Jr, Kronenberg HM, et al,. (1993). Cloned, stably expressed parathyroid hormone (PTH)/PTH-related peptide receptors activate multiple messenger signals and biological responses in LLC-PK1 kidney cells. Endocrinology 132: 2090-2098. (Pubitemid 23133257)
12. Caverzasio J, Palmer G, Suzuki A, Bonjour J, (1997). Mechanism of the mitogenic effect of fluoride on osteoblast-like cells: evidences for a G protein-dependent tyrosine phosphorylation process. J Bone Mineral Res 12: 1975-1983. (Pubitemid 27524474)
13. Cole JA, (1999). Parathyroid hormone activates mitogen-activated protein kinase in opossum kidney cells. Endocrinology 140: 5771-5779. (Pubitemid 30645366)
14. Costa T, Herz A, (1989). Antagonists with negative intrinsic activity at delta opioid receptors coupled to GTP-binding proteins. Proc Natl Acad Sci U S A 86: 7321-7325. (Pubitemid 19254452)
15. Dobnig H, Turner RT, (1995). Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136: 3632-3638.
16. Ferguson SS, (2001). Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharm Rev 53: 1-24. (Pubitemid 32173106)
17. Ferrari SL, Behar V, Chorev M, Rosenblatt M, Bisello A, (1999). Endocytosis of ligand-human parathyroid hormone receptor 1 complexes is protein kinase C-dependent and involves beta-arrestin2. Real-time monitoring by fluorescence microscopy. J Biol Chem 274: 29968-29975.
18. Ferrari SL, Pierroz DD, Glatt V, Goddard DS, Bianchi EN, Lin FT, et al,. (2005). Bone response to intermittent parathyroid hormone is altered in mice null for beta-Arrestin2. Endocrinology 146: 1854-1862. (Pubitemid 40396895)
19. Foord SM, Marshall FH, (1999). RAMPs: accessory proteins for seven transmembrane domain receptors. Trends Pharmacol Sci 20: 184-187.
20. Garcia-Ocana A, Gomez-Casero E, Penaranda C, Esbrit P, (1998). Parathyroid hormone-related protein increases DNA synthesis in proximal tubule cells by cyclic AMP- and protein kinase C-dependent pathways. Life Sci 62: 2267-2273. (Pubitemid 28273155)
21. Gardella TJ, Luck MD, Jensen GS, Schipani E, Potts JT Jr, Juppner H, (1996). Inverse agonism of amino-terminally truncated parathyroid hormone (PTH) and PTH-related peptide (PTHrP) analogs revealed with constitutively active mutant PTH/PTHrP receptors. Endocrinology 137: 3936-3941. (Pubitemid 26284669)
22. Gesty-Palmer D, Chen M, Reiter E, Ahn S, Nelson CD, Wang S, et al,. (2006). Distinct conformations of the parathyroid hormone receptor mediate G protein and beta-arrestin dependent activation of ERK1/2. J Biol Chem 281: 10856-10864. (Pubitemid 43855508)
23. Gesty-Palmer D, Flannery P, Yuan L, Corsino L, Spurney R, Lefkowitz RJ, et al,. (2009). A beta-Arrestin Biased Agonist of the Parathyroid Hormone Receptor (PTH1R) promotes bone formation independent of G protein activation. Science-Trans Med 1: 1ra1.
24. Giustina A, Mazziotti G, Canalis E, (2008). Growth Hormone, insulin-like growth factors, and the skeleton. Endocrine Rev 29: 535-559.
25. Hall RA, Lefkowitz RJ, (2002). Regulation of G protein-coupled receptor signaling by scaffold proteins. Circ Res 91: 672-680. (Pubitemid 35204949)
26. Hock JM, Gera I, (1992). Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone. J Bone Mineral Res 7: 65-72.
27. Iida-Klein A, Guo J, Takemura M, Drake MT, Potts JT Jr, Abou-Samra A, et al,. (1997). Mutations in the second cytoplasmic loop of the rat parathyroid hormone (PTH)/PTH-related protein receptor result in selective loss of PTH-stimulated phospholipase C activity. J Biol Chem 272: 6882-6889. (Pubitemid 27166385)
28. Ishizuya T, Yokose S, Hori M, Noda T, Suda T, Yoshiki S, et al,. (1997). Parathyroid Hormone Exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells. J Clin Invest 99: 2961-2970. (Pubitemid 27278673)
29. Jouishomme H, Whitfield JF, Chakravarthy B, Durkin JP, Gagnon L, Isaacs RJ, et al,. (1992). The protein kinase-C activation domain of the parathyroid hormone. Endocrinology 130: 53-60.
30. Jouishomme H, Whitfield JF, Gagnon L, MacLean S, Isaacs R, Chakravarthy B, et al,. (1994). Further definition of the protein kinase C activation domain of the parathyroid hormone. J Bone Miner Res 9: 943-949. (Pubitemid 24178077)
31. Juppner H, Abou-Samra AB, Freeman M, Kong XF, Schipani E, Richards J, et al,. (1991). A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science 254: 1024-1026. (Pubitemid 21917436)
32. Karlin A, (1967). On the application of 'a plausible model' of allosteric proteins to the receptor for acetylcholine. J Theor Biol 16: 306-320.
33. Kenakin T, (1995). Agonist-receptor efficacy. II. Agonist-trafficking of receptor signals. Trends Pharmacol Sci 16: 232-238.
34. Kenakin T, Miller LE, (2010). Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharm Rev 62: 265-304.
35. Kenakin TP, (1996). Receptor conformational induction versus selection: all part of the same energy landscape. Trends Pharmacol Sci 17: 190-191.
36. Koh AJ, Beecher CA, Rosol TJ, McCauley LK, (1999). 3′,5′- Cyclic adenosine monophosphate activation in osteoblastic cells: effects on parathyroid hormone-1 receptors and osteoblastic differentiation in vitro. Endocrinology 140: 3154-3162. (Pubitemid 30650631)
37. Kohout TA, Lin FS, Perry SJ, Conner DA, Lefkowitz RJ, (2001). beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc Natl Acad Sci U S A 98: 1601-1606. (Pubitemid 32165545)
38. Lau KHW, David JB, (1998). Molecular mechanism of action of fluoride on bone cells. J Bone Mineral Res 13: 1660-1667.
39. Laugwitz KL, Allgeier A, Offermanns S, Spicher K, Van Sande J, Dumont JE, et al,. (1996). The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. Proc Natl Acad Sci U S A 93: 116-120. (Pubitemid 26038113)
40. Lederer ED, Sohi SS, McLeish KR, (2000). Parathyroid hormone stimulates extracellular signal-regulated kinase (ERK) activity through two independent signal transduction pathways: role of ERK in sodium-phosphate cotransport. J Am Soc Nephrol 11: 222-231. (Pubitemid 30064845)
41. Lefkowitz RJ, (1993). G protein-coupled receptor kinases. Cell 74: 409-412. (Pubitemid 23244606)
42. Luttrell LM, Gesty-Palmer D, (2010). Beyond desensitization: physiological relevance of arrestin-dependent signaling. Pharm Rev 62: 305-330.
43. Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, Della Rocca GJ, et al,. (1999). Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science 283: 655-661.
44. Mahon MJ, Donowitz M, Yun CC, Segre GV, (2002). Na(+)/H(+) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. Nature 417: 858-861. (Pubitemid 34670333)
45. Maudsley S, Martin B, Luttrell LM, (2005). The origins of diversity and specificity in G protein-coupled receptor signaling. J Pharmacol Exp Ther 314: 485-494. (Pubitemid 41043828)
46. McDonnell DP, Connor CE, Wijayaratne A, Chang CY, Norris JD, (2002). Definition of the molecular and cellular mechanisms underlying the tissue-selective agonist/antagonist activities of selective estrogen receptor modulators. Recent Prog Horm Res 57: 295-316.
47. Orsini LS, Rousculp MD, Long SR, Wang S, (2005). Health Care utilization and expenditures in the United States: a study of osteoporosis-related fractures. Osteoporosis Int. 16: 359-371. (Pubitemid 40487393)
48. Pi M, Oakley RH, Gesty-Palmer D, Cruickshank RD, Spurney RF, Luttrell LM, et al,. (2005). beta-Arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization. Mol Endocrinol 19: 1078-1087. (Pubitemid 40397070)
49. Pierroz DD, Rufo A, Bianchi EN, Glatt V, Capulli M, Rucci N, et al,. (2009). beta-Arrestin2 regulates RANKL and ephrins gene expression in response to bone remodeling in mice. J Bone Mineral Res 24: 775-784.
50. Qin L, Raggatt LJ, Partridge NC, (2004). Parathyroid hormone: a double-edged sword for bone metabolism. Trends Endocrinol Metab 15: 60-65. (Pubitemid 38253007)
51. Quarles LD, Haupt DM, Davidai G, Middleton JP, (1993). Prostaglandin F2 alpha-induced mitogenesis in MC3T3-E1 osteoblasts: role of protein kinase-C-mediated tyrosine phosphorylation. Endocrinology 132: 1505-1513. (Pubitemid 23110519)
52. Samama P, Cotecchia S, Costa T, Lefkowitz RJ, (1993). A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model. J Biol Chem 268: 4625-4636. (Pubitemid 23081571)
53. Schmidt I, Dobnig H, Turner R, (1995). Intermittent parathyroid hormone treatment increases osteoblast number, steady state messenger ribonucleic acid levels for osteocalcin, and bone formation in tibial metaphysis of hypophysectomized female rats. Endocrinology 136: 5127-5134.
54. Soper DL, Milbank JBJ, Mieling GE, Dirr MJ, Kende AS, Cooper R, et al,. (2001). Synthesis and biological evaluation of prostaglandin-F alkylphosphinic acid derivatives as bone anabolic agents for the treatment of osteoporosis. J Med Chem 44: 4157-4169. (Pubitemid 33095322)
55. Sugimoto T, Kaji H, Nakaoka D, Yamauchi M, Yano S, Sugishita T, et al,. (2002). Effect of low-dose of recombinant human growth hormone on bone metabolism in elderly women with osteoporosis. Eur J Endocrinol 147: 339-348.
56. Swarthout JT, Doggett TA, Lemker JL, Partridge NC, (2001). Stimulation of extracellular signal-regulated kinases and proliferation in rat osteoblastic cells by parathyroid hormone is protein kinase C-dependent. J Biol Chem 276: 7586-7592.
57. Takasu H, Gardella TJ, Luck MD, Potts JT Jr, Bringhurst FR, (1999). Amino-terminal modifications of human parathyroid hormone (PTH) selectively alter phospholipase C signaling via the type 1 PTH receptor: implications for design of signal-specific PTH ligands. Biochemistry 38: 13453-13460.
58. Tam CS, Heersche JN, Murray TM, Parsons JA, (1982). Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. Endocrinology 110: 506-512. (Pubitemid 12162946)
59. Thron CD, (1973). On the analysis of pharmacological experiments in terms of an allosteric receptor model. Mol Pharmacol 9: 1-9.
60. Verheijen MH, Defize LH, (1997). Parathyroid hormone activates mitogen-activated protein kinase via a cAMP-mediated pathway independent of Ras. J Biol Chem 272: 3423-3429. (Pubitemid 27066840)
61. Vestergaard P, Jorgensen N, Schwarz P, Mosekilde L, (2008). Effects of treatment with fluoride on bone mineral density and fracture risk-a meta-analysis. Osteoporosis Int 19: 257-268.
62. Vilardaga JP, Krasel C, Chauvin S, Bambino T, Lohse MJ, Nissenson RA, (2002). Internalization determinants of the parathyroid hormone receptor differentially regulate beta-arrestin/receptor association. J Biol Chem 277: 8121-8129. (Pubitemid 34968266)
63. Wei H, Ahn S, Shenoy SK, Karnik S, Hunyady L, Luttrell LM, et al,. (2003). Independent G protein and beta-Arrestin2 mediated activation of ERK by angiotensin. Proc Natl Acad Sci U S A 100: 10782-10787.
64. Weiss JM, Morgan PH, Lutz MW, Kenakin TP, (1996). The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy. J Theor Biol 181: 381-397. (Pubitemid 26333834)
65. Whitfield JF, Morley P, (1995). Small bone-building fragments of parathyroid hormone: new therapeutic agents for osteoporosis. Trends Pharmacol Sci 16: 382-386.
66. Wisler JW, DeWire SM, Whalen EJ, Violin JD, Drake MT, Ahn S, et al,. (2007). A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A 104: 16657-16662. (Pubitemid 350211072)