Comparing the molecular pharmacology of CGRP and adrenomedullin

Current Protein and Peptide Science

Volumn 14, Issue 5, 2013, Pages 358-374

  Woolley, Michael J ^a   Conner, Alex C ^a  

^a UNIVERSITY OF WARWICK   (United Kingdom)

Author keywords

Adrenomedullin; Am; Cgrp; Clr; Family b; Gpcr; Ramp; Receptor activation

Indexed keywords

ADENOSINE RECEPTOR; ADRENOMEDULLIN RECEPTOR; ALANINE; BETA 2 ADRENERGIC RECEPTOR; BETA ARRESTIN 2; CALCITONIN GENE RELATED PEPTIDE; CALCITONIN RECEPTOR; CALCITONIN RECEPTOR LIKE RECEPTOR; ENDOTHELIN CONVERTING ENZYME; LIGAND; MITOGEN ACTIVATED PROTEIN KINASE; OLCEGEPANT; PHOSPHOLIPASE C; PROLINE; RECEPTOR ACTIVITY MODIFYING PROTEIN; RECEPTOR ACTIVITY MODIFYING PROTEIN 1; RECEPTOR ACTIVITY MODIFYING PROTEIN 2; RECEPTOR ACTIVITY MODIFYING PROTEIN 3; TELCAGEPANT; TYROSINE; VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 1;

CHEMICAL PHENOMENA; DISULFIDE BOND; GENE MUTATION; HUMAN; HYDROGEN BOND; INTRACELLULAR SIGNALING; LIGAND BINDING; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN INTERACTION; RECEPTOR AFFINITY; REVIEW; SEQUENCE ALIGNMENT; SEQUENCE HOMOLOGY; STRUCTURAL PROTEOMICS;

ADRENOMEDULLIN; CALCITONIN GENE-RELATED PEPTIDE; HUMANS; PROTEIN BINDING; RECEPTORS, ADRENOMEDULLIN; RECEPTORS, CALCITONIN GENE-RELATED PEPTIDE; VASODILATOR AGENTS;

EID: 84882662263     PISSN: 13892037     EISSN: 18755550     Source Type: Journal    
DOI: 10.2174/13892037113149990053     Document Type: Review

References (90)

1. Poyner, D. R.; Sexton, P. M.; Marshall, I.; Smith, D. M.; Quirion, R.; Born, W.; Muff, R.; Fischer, J. A.; and Foord, S. M. International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol. Rev., 2002, 54, 233-246.
2. Pal, K.; Melcher, K.; and Xu, H. E. Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors, Acta. Pharmacol. Sin., 2012,33, 300-311.
3. Conner, A. C.; Hay, D. L.; Howitt, S. G.; Kilk, K.; Langel, U.; Wheatley, M.; Smith, D. M.; and Poyner, D. R. Interaction of calcitonin-gene-related peptide with its receptors. Biochem. Soc. Trans., 2002, 30, 451-455.
4. Pérez-Castells, J.; Martín-Santamaría, S.; Nieto, L.; Ramos, A.; Martínez, A.; Pascual-Teresa, B.; and Jiménez-Barbero, J. Structure of micelle-bound adrenomedullin: a first step toward the analysis of its interactions with receptors and small molecules. Biopolymers, 2012, 97, 45-53.
5. Walker, C. S.; Conner, A. C.; Poyner, D. R.; and Hay, D. L. Regulation of signal transduction by calcitonin gene-related peptide receptors. Trends Pharmacol. Sci., 2010, 31, 476-483.
6. McLatchie, L.; Fraser, N.; Main, M.; Wise, A.; Brown, J.; Thompson, N.; Solari, R.; Lee, M.; and Foord, S. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature,1998, 393, 333-339.
7. van Rossum, D.; Hanisch, U. K.; and Quirion, R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci. Biobehav. Rev., 1997, 21, 649-678.
8. Brain, S. D.; and Grant, A. D. Vascular actions of calcitonin generelated peptide and adrenomedullin. Physiol. Rev., 2004, 84, 903-934.
9. Durham, P. L. Inhibition of calcitonin gene-related peptide function: a promising strategy for treating migraine. Headache, 2008, 48, 1269-1275.
10. Amara, S. G.; Jonas, V.; Rosenfeld, M. G.; Ong, E. S.; and Evans, R. M. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature, 1982, 298, 240-244.
11. Steenbergh, P. H.; Höppener, J. W.; Zandberg, J.; Lips, C. J.; and Jansz, H. S. A second human calcitonin/CGRP gene. FEBS Lett.,1985,183, 403-407.
12. Mulderry, P. K.; Ghatei, M. A.; Spokes, R. A.; Jones, P. M.; Pierson, A. M.; Hamid, Q. A.; Kanse, S.; Amara, S. G.; Burrin, J. M.; and Legon, S. Differential expression of alpha-CGRP and beta-CGRP by primary sensory neurons and enteric autonomic neurons of the rat. Neuroscience, 1988, 25, 195-205.
13. Petermann, J. B.; Born, W.; Chang, J. Y.; and Fischer, J. A. Identification in the human central nervous system, pituitary, and thyroid of a novel calcitonin gene-related peptide, and partial amino acid sequence in the spinal cord. J. Biol. Chem., 1987, 262, 542-545.
14. Boulanger, Y.; Khiat, A.; Chen, Y.; Senécal, L.; Tu, Y.; St-Pierre, S.; and Fournier, A. Structure of human calcitonin gene-related peptide [hCGRP] and of its antagonist hCGRP 8-37 as determined by NMR and molecular modeling. Pept. Res., 1995, 8, 206-213.
15. Sagoo, J. K.; Bose, C.; Beeley, N. R.; and Tendler, S. J. Structural studies on the [Bu[t]-Cys18][19-37]-fragment of human betacalcitonin-gene-related peptide. Biochem. J.,1991, 280[ Pt 1], 147-150.
16. Robinson, S. D.; Aitken, J. F.; Bailey, R. J.; Poyner, D. R.; and Hay, D. L. Novel peptide antagonists of adrenomedullin and calcitonin gene-related peptide receptors: identification, pharmacological characterization, and interactions with position 74 in receptor activity-modifying protein 1/3. J. Pharmacol. Exp. Ther., 2009, 331, 513-521.
17. Kitamura, K.; Kangawa, K.; Kawamoto, M.; Ichiki, Y.; Nakamura, S.; Matsuo, H.; and Eto, T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Commun., 1993,192, 553-560.
18. Ishimitsu, T.; Ono, H.; Minami, J.; and Matsuoka, H. Pathophysiologic and therapeutic implications of adrenomedullin in cardiovascular disorders. Pharmacol. Ther., 2006,111, 909-927.
19. Kuwasako, K.; Kitamura, K.; Nagata, S.; Hikosaka, T.; Takei, Y.; and Kato, J. Shared and separate functions of the RAMP-based adrenomedullin receptors. Peptides, 2011, 32, 1540-1550.
20. Sugo, S.; Minamino, N.; Kangawa, K.; Miyamoto, K.; Kitamura, K.; Sakata, J.; Eto, T.; and Matsuo, H. Endothelial cells actively synthesize and secrete adrenomedullin. Biochem. Biophys. Res. Commun., 1994, 201, 1160-1166.
21. Sugo, S.; Minamino, N.; Shoji, H.; Kangawa, K.; Kitamura, K.; Eto, T.; and Matsuo, H. Production and secretion of adrenomedullin from vascular smooth muscle cells: augmented production by tumor necrosis factor-alpha, Biochem. Biophys. Res. Commun., 1994, 203, 719-726.
22. Sugo, S.; Minamino, N.; Shoji, H.; Kangawa, K.; Kitamura, K.; Eto, T.; and Matsuo, H. Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. Biochem. Biophys. Res. Commun., 1995, 207, 25-32.
23. Eguchi, S.; Hirata, Y.; Iwasaki, H.; Sato, K.; Watanabe, T. X.; Inui, T.; Nakajima, K.; Sakakibara, S.; and Marumo, F. Structureactivity relationship of adrenomedullin, a novel vasodilatory peptide, in cultured rat vascular smooth muscle cells. Endocrinology, 1994,135, 2454-2458.
24. Muff, R.; Born, W.; and Fischer, J. A. Adrenomedullin selectivity of calcitonin-like receptor/receptor activity modifying proteins. Hypertens. Res., 2003, 26 Suppl, S3-S8.
25. Roh, J.; Chang, C. L.; Bhalla, A.; Klein, C.; Hsu, S. Y. Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activitymodifying protein receptor complexes. J. Biol. Chem., 2004, 279, 7264-7274.
26. Takei, Y.; Hyodo, S.; Katafuchi, T.; Minamino, N. Novel fishderived adrenomedullin in mammals: structure and possible function. Peptides, 2004, 25, 1643-1656.
27. Hong, Y.; Hay, D. L.; Quirion, R.; Poyner, D. R. The pharmacology of adrenomedullin 2/intermedin. Br. J. Pharmacol., 2012, 166, 110-120.
28. Yang, J. H.; Jia, Y. X.; Pan, C. S.; Zhao, J.; Ouyang, M.; Yang, J.; Chang, J. K.; Tang, C. S.; Qi, Y. F. Effects of intermedin[1-53] on cardiac function and ischemia/reperfusion injury in isolated rat hearts. Biochem. Biophys. Res. Commun., 2005, 327, 713-719.
29. Njuki, F.; Nicholl, C. G.; Howard, A.; Mak, J. C.; Barnes, P. J.; Girgis, S. I.; Legon, S. A new calcitonin-receptor-like sequence in rat pulmonary blood vessels. Clin. Sci.[Lond]., 1993, 85, 385-388.
30. Flühmann, B.; Muff, R.; Hunziker, W.; Fischer, J. A.; Born, W. A human orphan calcitonin receptor-like structure. Biochem. Biophys. Res. Commun., 1995, 206, 341-347.
31. Aiyar, N.; Rand, K.; Elshourbagy, N. A.; Zeng, Z.; Adamou, J. E.; Bergsma, D. J.; Li, Y. A cDNA encoding the calcitonin generelated peptide type 1 receptor. J. Biol. Chem., 1996, 271, 11325-11329.
32. Sexton, P. M.; Albiston, A.; Morfis, M.; Tilakaratne, N. Receptor activity modifying proteins. Cell Signal, 2001,13, 73-83.
33. Bomberger, J. M.; Parameswaran, N.; Hall, C. S.; Aiyar, N.; and Spielman, W. S. Novel function for receptor activity-modifying proteins [RAMPs] in post-endocytic receptor trafficking. J. Biol. Chem., 2005, 280, 9297-9307.
34. Kuwasako, K.; Shimekake, Y.; Masuda, M.; Nakahara, K.; Yoshida, T.; Kitaura, M.; Kitamura, K.; Eto, T.; and Sakata, T. Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling. J. Biol. Chem., 2000, 275, 29602-29609.
35. Bühlmann, N.; Aldecoa, A.; Leuthäuser, K.; Gujer, R.; Muff, R.; Fischer, J. A.; Born, W. Glycosylation of the calcitonin receptorlike receptor at Asn[60] or Asn[112] is important for cell surface expression. FEBS Lett., 2000, 486, 320-324.
36. Kamitani, S.; Sakata, T. Glycosylation of human CRLR at Asn123 is required for ligand binding and signaling. Biochim. Biophys. Acta., 2001, 1539,131-139.
37. ter Haar, E.; Koth, C. M.; Abdul-Manan, N.; Swenson, L.; Coll, J. T.; Lippke, J. A.; Lepre, C. A.; Garcia-Guzman, M.; Moore, J. M. Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism. Structure, 2010,18, 1083-1093.
38. Steiner, S.; Muff, R.; Gujer, R.; Fischer, J. A.; and Born, W. The transmembrane domain of receptor-activity-modifying protein 1 is essential for the functional expression of a calcitonin gene-related peptide receptor. Biochemistry, 2002, 41, 11398-11404.
39. Aldecoa, A.; Gujer, R.; Fischer, J. A.; and Born, W. Mammalian calcitonin receptor-like receptor/receptor activity modifying protein complexes define calcitonin gene-related peptide and adrenomedullin receptors in Drosophila Schneider 2 cells. FEBS Lett., 2000, 471, 156-160.
40. Kusano, S.; Kukimoto-Niino, M.; Hino, N.; Ohsawa, N.; Okuda, K.; Sakamoto, K.; Shirouzu, M.; Shindo, T.; and Yokoyama, S. Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci., 2012, 21, 199-210.
41. Flahaut, M.; Rossier, B. C.; and Firsov, D. Respective roles of calcitonin receptor-like receptor [CRLR] and receptor activitymodifying proteins [RAMP] in cell surface expression of CRLR/RAMP heterodimeric receptors. J. Biol Chem., 2002, 277, 14731-14737.
42. Christopoulos, A.; Christopoulos, G.; Morfis, M.; Udawela, M.; Laburthe, M.; Couvineau, A.; Kuwasako, K.; Tilakaratne, N.; and Sexton, P. M. [2003] Novel receptor partners and function of receptor activity-modifying proteins. J. Biol. Chem., 278, 3293-3297.
43. Wootten, D.; Lindmark, H.; Kadmiel, M.; Willcockson, H.; Caron, K. M.; Barwell, J.; Drmota, T.; and Poyner, D.; R. Receptor Activity Modifying Proteins [RAMPs] Interact with the VPAC[2] Receptor and CRF[1] Receptors and modulate their function. Br. J. Pharmacol., 2012.
44. Egea, S. C.; and Dickerson, I. M. Direct interactions between calcitonin-like receptor [CLR] and CGRP-receptor component protein [RCP] regulate CGRP receptor signaling. Endocrinology, 2012,153, 1850-1860.
45. Hay, D. L.; Poyner, D. R.; and Smith, D. M. Desensitisation of adrenomedullin and CGRP receptors. Regul Pept., 2003,112, 139-145.
46. Main, M. J.; Brown, J.; Brown, S.; Fraser, N. J.; and Foord, S. M. The CGRP receptor can couple via pertussis toxin sensitive and insensitive G proteins. FEBS Lett., 1998, 441, 6-10.
47. Drissi, H.; Lasmoles, F.; Le Mellay, V.; Marie, P. J.; and Lieberherr, M. Activation of phospholipase C-beta1 via Galphaq/11 during calcium mobilization by calcitonin gene-related peptide. J. Biol. Chem., 1998, 273, 20168-20174.
48. Drissi, H.; Lieberherr, M.; Hott, M.; Marie, P. J.; and Lasmoles, F. Calcitonin gene-related peptide [CGRP] increases intracellular free Ca2+ concentrations but not cyclic AMP formation in CGRP receptor-positive osteosarcoma cells [OHS-4]. Cytokine, 1999,11, 200-207.
49. Nishimatsu, H.; Suzuki, E.; Nagata, D.; Moriyama, N.; Satonaka, H.; Walsh, K.; Sata, M.; Kangawa, K.; Matsuo, H.; Goto, A.; Kitamura, T.; and Hirata, Y. Adrenomedullin induces endotheliumdependent vasorelaxation via the phosphatidylinositol 3-kinase/Akt-dependent pathway in rat aorta. Circ. Res., 2001, 89, 63-70.
50. Pioszak, A.; and Xu, H. Molecular recognition of parathyroid hormone by its G protein-coupled receptor. Proc. Natl. Acad. Sci.U S A., 2008, 105, 5034-5039.
51. Parthier, C.; Kleinschmidt, M.; Neumann, P.; Rudolph, R.; Manhart, S.; Schlenzig, D.; Fanghänel, J.; Rahfeld, J.; Demuth, H.; and Stubbs, M. Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor. Proc. Natl. Acad. Sci. U S A., 2007, 104, 13942-13947.
52. Steiner, S.; Born, W.; Fischer, J. A.; and Muff, R. The function of conserved cysteine residues in the extracellular domain of human receptor-activity-modifying protein. FEBS Lett., 2003, 555, 285-290.
53. Kusano, S.; Kukimoto-Niino, M.; Akasaka, R.; Toyama, M.; Terada, T.; Shirouzu, M.; Shindo, T.; and Yokoyama, S. Crystal structure of the human receptor activity-modifying protein 1 extracellular domain. Protein Sci., 2008, 17, 1907-1914.
54. Conner, A. C.; Simms, J.; Barwell, J.; Wheatley, M.; and Poyner, D. R. Ligand binding and activation of the CGRP receptor. Biochem. Soc. Trans., 2007,35, 729-732.
55. Watkins, H. A.; Au, M.; and Hay, D. L. The structure of secretin family GPCR peptide ligands: implications for receptor pharmacology and drug development. Drug Discov. Today, 2012, 17, 1006-1014.
56. Neumann, J.; Couvineau, A.; Murail, S.; Lacapère, J.; Jamin, N.; and Laburthe, M. Class-B GPCR activation: is ligand helix-capping the key?. Trends Biochem. Sci., 2008, 33, 314-319.
57. Parthier, C.; Reedtz-Runge, S.; Rudolph, R.; and Stubbs, M. Passing the baton in class B GPCRs: peptide hormone activation via helix induction?. Trends Biochem. Sci., 2009, 34, 303-310.
58. Poyner, D. R.; Soomets, U.; Howitt, S. G.; and Langel, U. Structural determinants for binding to CGRP receptors expressed by human SK-N-MC and Col 29 cells: studies with chimeric and other peptides. Br. J. Pharmacol., 1998,124, 1659-1666.
59. O'Connell, J. P.; Kelly, S. M.; Raleigh, D. P.; Hubbard, J. A.; Price, N. C.; Dobson, C. M.; and Smith, B. J. On the role of the Cterminus of alpha-calcitonin-gene-related peptide [alpha CGRP]. The structure of des-phenylalaninamide37-alpha CGRP and its interaction with the CGRP receptor. Biochem. J., 1993, 291[ Pt 1], 205-210.
60. Banerjee, S.; Evanson, J.; Harris, E.; Lowe, S. L.; Thomasson, K. A.; and Porter, J. E. Identification of specific calcitonin-like receptor residues important for calcitonin gene-related peptide high affinity binding. BMC Pharmacol., 2006, 6-9.
61. Lang, M.; De Pol, S.; Baldauf, C.; Hofmann, H. J.; Reiser, O.; and Beck-Sickinger, A. G. Identification of the key residue of calcitonin gene related peptide [CGRP] 27-37 to obtain antagonists with picomolar affinity at the CGRP receptor. J. Med. Chem., 2006, 49, 616-624.
62. Hershey, J. C.; Corcoran, H. A.; Baskin, E. P.; Salvatore, C. A.; Mosser, S.; Williams, T. M.; Koblan, K. S.; Hargreaves, R. J.; and Kane, S. A. Investigation of the species selectivity of a nonpeptide CGRP receptor antagonist using a novel pharmacodynamic assay. Regul. Pept., 2005, 127, 71-77.
63. Salvatore, C. A.; Hershey, J. C.; Corcoran, H. A.; Fay, J. F.; Johnston, V. K.; Moore, E. L.; Mosser, S. D.; Burgey, C. S.; Paone, D. V.; Shaw, A. W.; Graham, S. L.; Vacca, J. P.; Williams, T. M.; Koblan, K. S.; and Kane, S. A. Pharmacological characterization of MK-0974 [N-[[3R,6S]-6-[2,3-difluorophenyl]-2-oxo-1-[2,2,2-trifluoroethyl]azepan-3-yl]-4-[2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl]piperidine-1-carboxamide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine. J. Pharmacol. Exp. Ther., 2008, 324, 416-421.
64. Koller, D.; Born, W.; Leuthäuser, K.; Flühmann, B.; McKinney, R. A.; Fischer, J. A.; and Muff, R. The extreme N-terminus of the calcitonin-like receptor contributes to the selective interaction with adrenomedullin or calcitonin gene-related peptide. FEBS Lett., 2002, 531, 464-468.
65. Barwell, J.; Miller, P. S.; Donnelly, D.; and Poyner, D. R. Mapping interaction sites within the N-terminus of the calcitonin generelated peptide receptor; the role of residues 23-60 of the calcitonin receptor-like receptor. Peptides, 2010, 31, 170-176.
66. Ittner, L. M.; Luessi, F.; Koller, D.; Born, W.; Fischer, J. A.; and Muff, R. Aspartate[69] of the calcitonin-like receptor is required for its functional expression together with receptor-activitymodifying proteins 1 and 2. Biochem. Biophys. Res. Commun., 2004, 319, 1203-1209.
67. Simms, J.; Hay, D. L.; Bailey, R. J.; Konycheva, G.; Bailey, G.; Wheatley, M.; and Poyner, D. R. Structure-function analysis of RAMP1 by alanine mutagenesis. Biochemistry, 2009, 48, 198-205.
68. Mallee, J. J.; Salvatore, C. A.; LeBourdelles, B.; Oliver, K. R.; Longmore, J.; Koblan, K. S.; and Kane, S. A. Receptor activitymodifying protein 1 determines the species selectivity of nonpeptide CGRP receptor antagonists. The Journal of biological chemistry, 2002, 277, 14294-14298.
69. Hay, D. L.; Christopoulos, G.; Christopoulos, A.; and Sexton, P. M. Determinants of 1-piperidinecarboxamide, N-[2-[[5-amino-l-[[4-[4-pyridinyl]-l-piperazinyl]carbonyl]pentyl]amino]-1-[[3,5-dibromo-4-hydroxyphenyl]methyl]-2-oxoethyl]-4-[1,4-dihydro-2-oxo-3[2H]-quinazolinyl] [BIBN4096BS] affinity for calcitonin generelated peptide and amylin receptors--the role of receptor activity modifying protein 1, Mol.Pharmacol., 2006, 70, 1984-1991.
70. Qi, T.; Ly, K.; Poyner, D. R.; Christopoulos, G.; Sexton, P. M.; and Hay, D. L. Structure-function analysis of amino acid 74 of human RAMP1 and RAMP3 and its role in peptide interactions with adrenomedullin and calcitonin gene-related peptide receptors. Peptides, 2011, 32, 1060-1067.
71. Qi, T.; Christopoulos, G.; Bailey, R. J.; Christopoulos, A.; Sexton, P. M.; and Hay, D. L. Identification of N-terminal receptor activitymodifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. Molecular pharmacology, 2008, 74, 1059-1071.
72. Moore, E. L.; Gingell, J. J.; Kane, S. A.; Hay, D. L.; and Salvatore, C. A. Mapping the CGRP receptor ligand binding domain: tryptophan-84 of RAMP1 is critical for agonist and antagonist binding. Biochem. Biophys. Res. Commun., 2010, 394, 141-145.
73. Kuwasako, K.; Kitamura, K.; Nagoshi, Y.; Cao, Y. N.; and Eto, T. Identification of the human receptor activity-modifying protein 1 domains responsible for agonist binding specificity. J. Biol. Chem.,2003,278, 22623-22630.
74. Watanabe, T. X.; Itahara, Y.; Inui, T.; Yoshizawa-Kumagaye, K.; Nakajima, K.; and Sakakibara, S. Vasopressor activities of Nterminal fragments of adrenomedullin in anesthetized rat. Biochem. Biophys. Res. Commun., 1996, 219, 59-63.
75. Kuwasako, K.; Kitamura, K.; Nagata, S.; and Kato, J. Functions of the extracellular histidine residues of receptor activity-modifying proteins vary within adrenomedullin receptors. Biochemical and biophysical research communications, 2008, 377, 109-113.
76. Barwell, J.; Conner, A.; and Poyner, D. R. Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function. Biochem. Biophys. Acta., 2011, 1813, 1906-1916.
77. Kuwasako, K.; Kitamura, K.; Uemura, T.; Nagoshi, Y.; Kato, J.; and Eto, T. The function of extracellular cysteines in the human adrenomedullin receptor. Hypertens. Res., 2003, 26 Suppl, S25-31.
78. Conner, A.; Hay, D.; Simms, J.; Howitt, S.; Schindler, M.; Smith, D.; Wheatley, M.; and Poyner, D. A key role for transmembrane prolines in calcitonin receptor-like receptor agonist binding and signalling: implications for family B G-protein-coupled receptors. Mol. Pharmacol., 2005, 67, 20-31.
79. Sheikh, S.; Vilardarga, J.; Baranski, T.; Lichtarge, O.; Iiri, T.; Meng, E.; Nissenson, R. and Bourne, H. Similar structures and shared switch mechanisms of the beta2-adrenoceptor and the parathyroid hormone receptor. Zn[II] bridges between helices III and VI block activation. J. Biol. Chem., 1999, 274, 17033-17041.
80. Kuwasako, K.; Hay, D. L.; Nagata, S.; Hikosaka, T.; Kitamura, K.; and Kato, J. The third extracellular loop of the human calcitonin receptor-like receptor is crucial for the activation of adrenomedullin signalling. Br. J. Pharmacol., 2012,166, 137-150.
81. Harikumar, K. G.; Simms, J.; Christopoulos, G.; Sexton, P. M.; and Miller, L. J. Molecular basis of association of receptor activitymodifying protein 3 with the family B G protein-coupled secretin receptor. Biochemistry, 2009, 48, 11773-11785.
82. Conner, A.; Simms, J.; Conner, M.; Wootten, D.; Wheatley, M.; and Poyner, D. Diverse functional motifs within the three intracellular loops of the CGRP1 receptor. Biochemistry, 2006, 45, 12976-12985.
83. Conner, A.; Simms, J.; Howitt, S.; Wheatley, M.; and Poyner, D. The second intracellular loop of the calcitonin gene-related peptide receptor provides molecular determinants for signal transduction and cell surface expression. J. Biol. Chem., 2006, 281, 1644-1651.
84. Evans, B. N.; Rosenblatt, M. I.; Mnayer, L. O.; Oliver, K. R.; and Dickerson, I. M. CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors. J. Biol. Chem., 2000, 275, 31438-31443.
85. Prado, M. A.; Evans-Bain, B.; Oliver, K. R.; and Dickerson, I. M. The role of the CGRP-receptor component protein [RCP] in adrenomedullin receptor signal transduction. Peptides, 2001, 22, 1773-1781.
86. Conner, M.; Hicks, M.; Dafforn, T.; Knowles, T.; Ludwig, C.; Staddon, S.; Overduin, M.; Günther, U.; Thome, J.; Wheatley, M.; Poyner, D.; and Conner, A. Functional and biophysical analysis of the C-terminus of the CGRP-receptor; a family B GPCR. Biochemistry, 2008, 47, 8434-8444.
87. Padilla, B. E.; Cottrell, G. S.; Roosterman, D.; Pikios, S.; Muller, L.; Steinhoff, M.; and Bunnett, N. W. Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and beta-arrestins. J. Cell Biol., 200, 179, 981-997.
88. Cottrell, G. S.; Padilla, B.; Pikios, S.; Roosterman, D.; Steinhoff, M.; Grady, E. F.; and Bunnett, N. W. Post-endocytic sorting of calcitonin receptor-like receptor and receptor activity-modifying protein 1. J. Biol. Chem., 2007, 282, 12260-12271.
89. Kuwasako, K.; Kitamura, K.; Nagata, S.; Hikosaka, T.; and Kato, J. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2. Biochem. Biophys. Res. Commun.,2010, 392, 380-385.
90. Kuwasako, K.; Kitamura, K.; Nagata, S.; Nozaki, N.; and Kato, J. Characterization of the single transmembrane domain of human receptor activity-modifying protein 3 in adrenomedullin receptor internalization. Biochem. Biophys. Res. Commun., 2012, 420, 582-587.