Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling

Molecular Endocrinology

Volumn 19, Issue 9, 2005, Pages 2400-2411

  Holst, Birgitte ^a   Brandt, Erik ^a   Bach, Anders ^a   Heding, Anders ^b   Schwartz, Thue W ^a,b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b 7TM Pharma A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

3 AMINO 3 METHYL N [2,3,4,5 TETRAHYDRO 2 OXO 1 [[2' (1H TETRAZOL 5 YL) 1,1' BIPHENYL 4 YL]METHYL] 1H 1 BENZAZEPIN 3 YL]BUTANAMIDE; CALCIUM; GHRELIN; GROWTH HORMONE SECRETAGOGUE; HISTIDYL DEXTRO TRYPTOPHYLALANYLTRYPTOPHYL DEXTRO PHENYLALANYLLYSINAMIDE; IBUTAMOREN; INOSITOL PHOSPHATE; RETINA S ANTIGEN;

ALLOSTERISM; ARTICLE; BINDING AFFINITY; CALCIUM MOBILIZATION; CYCLIC AMP RESPONSIVE ELEMENT; DRUG BINDING; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; PRIORITY JOURNAL; SERUM RESPONSIVE ELEMENT; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TURNOVER TIME;

ALLOSTERIC REGULATION; AMINO ACID SEQUENCE; ANIMALS; ARRESTIN; BENZAZEPINES; CALCIUM; CREB-BINDING PROTEIN; HUMANS; INDOLES; INOSITOL PHOSPHATES; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; OLIGOPEPTIDES; PEPTIDE HORMONES; RECEPTORS, G-PROTEIN-COUPLED; RESPONSE ELEMENTS; SERUM RESPONSE ELEMENT; SIGNAL TRANSDUCTION; SPIRO COMPOUNDS; TETRAZOLES; TRANSCRIPTION, GENETIC;

EID: 24344479915     PISSN: 08888809     EISSN: 08888809     Source Type: Journal    
DOI: 10.1210/me.2005-0059     Document Type: Article

References (44)

1. Bowers CY, Momany F, Reynolds GA, Chang D, Hong A, Chang K 1980 Structure-activity relationships of a synthetic pentapeptide that specifically releases growth hormone in vitro. Endocrinology 106:663-667
2. Bowers CY, Momany FA, Reynolds GA, Hong A 1984 On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology 114:1537-1545
3. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K 1999 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656-660
4. Patchett AA, Nargund RP, Tata JR, Chen MH, Barakat KJ, Johnston DB, Cheng K, Chan WW, Butler B, Hickey G 1995 Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proc Natl Acad Sci USA 92:7001-7005
5. Smith RG, Cheng K, Schoen WR, Pong SS, Hickey G, Jacks T, Butler B, Chan WW, Chaung LY, Judith F 1993 A nonpeptidyl growth hormone secretagogue. Science 260:1640-1643
6. Murphy MG, Weiss S, McClung M, Schnitzer T, Cerchio K, Connor J, Krupa D, Gertz BJ 2001 Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 86:1116-1125
7. Smith RG, Van Der Ploeg LH, Howard AD, Feighner SD, Cheng K, Hickey GJ, Wyvratt Jr MJ, Fisher MH, Nargund RP, Patchett AA 1997 Peptidomimetic regulation of growth hormone secretion. Endocr Rev 18:621-645
8. Kojima M, Hosoda H, Matsuo H, Kangawa K 2001 Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab 12:118-122
9. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS 2001 A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50:1714-1719
10. Neary NM, Small CJ, Wren AM, Lee JL, Druce MR, Palmieri C, Frost GS, Ghatei MA, Coombes RC, Bloom SR 2004 Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 89:2832-2836
11. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR 2001 Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992
12. Nagaya N, Moriya J, Yasumura Y, Uematsu M, Ono F, Shimizu W, Ueno K, Kitakaze M, Miyatake K, Kangawa K 2004 Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 110:3674-3679
13. Peeters TL 2003 Central and peripheral mechanisms by which ghrelin regulates gut motility. J Physiol Pharmacol 54(Suppl 4):95-103
14. Yoshihara F, Kojima M, Hosoda H, Nakazato M, Kangawa K 2002 Ghrelin: a novel peptide for growth hormone release and feeding regulation. Curr Opin Clin Nutr Metab Care 5:391-395
15. Cummings DE, Foster KE 2003 Ghrelin-leptin tango in body-weight regulation. Gastroenterology 124:1532-1535
16. Holst B, Schwartz TW 2004 Constitutive ghrelin receptor activity as a signaling set-point in appetite regulation. Trends Pharmacol Sci 25:113-117
17. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong SS, Chaung LY, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJ, Dean DC, Melillo DG, Van Der Ploeg LH 1996 A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273:974-977
18. Holst B, Cygankiewicz A, Halkjar JT, Ankersen M, Schwartz TW 2003 High constitutive signaling of the ghrelin receptor-identification of a potent inverse agonist. Mol Endocrinol 17:2201-2210
19. Holst B, Holliday ND, Bach A, Elling CE, Cox HM, Schwartz TW 2004 Common structural basis for constitutive activity of the ghrelin receptor family. J Biol Chem 279:53806-53817
20. Matthews RP, Guthrie CR, Wailes LM, Zhao X, Means AR, McKnight GS 1994 Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Mol Cell Biol 14:6107-6116
21. Singh LP, Andy J, Anyamale V, Greene K, Alexander M, Crook ED 2001 Hexosamine-induced fibronectin protein synthesis in mesangial cells is associated with increases in cAMP responsive element binding (CREB) phosphorylation and nuclear CREB: the involvement of protein kinases A and C. Diabetes 50:2355-2362
22. Lefkowitz RJ, Whalen EJ 2004 β-Arrestins: traffic cops of cell signaling. Curr Opin Cell Biol 16:162-168
23. Vrecl M, Jorgensen R, Pogacnik A, Heding A 2004 Development of a BRET2 screening assay using β-arrestin 2 mutants. J Biomol Screen 9:322-333
24. Bruns RF, Fergus JH 1990 Allosteric enhancement of adenosine A1 receptor binding and function by 2-amino-3-benzoylthiophenes. Mol Pharm 38:939-949
25. Birdsall NJ, Farries T, Gharagozloo P, Kobayashi S, Lazareno S, Sugimoto M 1999 Subtype-selective positive cooperative interactions between brucine analogs and acetylcholine at muscarinic receptors: functional studies. Mol Pharmacol 55:778-786
26. Lazareno S, Popham A, Birdsall NJ 2000 Allosteric interactions of staurosporine and other indolocarbazoles with N-[methyl-(3)H]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site. Mol Pharmacol 58:194-207
27. Leppik RA, Mynett A, Lazareno S, Birdsall NJ 2000 Allosteric interactions between the antagonist prazosin and amiloride analogs at the human α(1A)-adrenergic receptor. Mol Pharmacol 57:436-445
28. Holst B, Elling CE, Schwartz TW 2002 Metal-ion mediated agonism and agonist-enhancement in the melanocortin MC1 and MC4 receptors. J Biol Chem 277:47662-47670
29. Binet V, Brajon C, Le Corre L, Acher F, Pin JP, Prezeau L 2004 The heptahelical domain of GABA(B2) is activated directly by CGP7930, a positive allosteric modulator of the GABA(B) receptor. J Biol Chem 279:29085-29091
30. Suzuki Y, Moriyoshi E, Tsuchiya D, Jingami H 2004 Negative cooperativity of glutamate binding in the dimeric metabotropic glutamate receptor subtype 1. J Biol Chem 279:35526-35534
31. Petrel C, Kessler A, Dauban P, Dodd RH, Rognan D, Ruat M 2004 Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J Biol Chem 279:18990-18997
32. Lazareno S, Popham A, Birdsall NJ 2002 Analogs of WIN 62,577 define a second allosteric site on muscarinic receptors. Mol Pharmacol 62:1492-1505
33. Heding A, Elling CE, Schwartz TW 2002 Novel method for the study of receptor Ca2+ signalling exemplified by the NK1 receptor. J Recept Signal Transduct Res 22:241-252
34. Birdsall NJ, Lazareno S, Popham A, Saldanha J 2001 Multiple allosteric sites on muscarinic receptors. Life Sci 68:2517-2524
35. Pin JP, Kniazeff J, Binet V, Liu J, Maurel D, Galvez T, Duthey B, Havlickova M, Blahos J, Prezeau L, Rondard P 2004 Activation mechanism of the heterodimeric GABA(B) receptor. Biochem Pharmacol 68:1565-1572
36. Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K 2000 Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407:971-977
37. Angers S, Salahpour A, Bouvier M 2002 Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. Annu Rev Pharmacol Toxicol 42:409-435
38. Hubbell WL, Altenbach C, Hubbell CM, Khorana HG 2003 Rhodopsin structure, dynamics, and activation: a perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking. Adv Protein Chem 63:243-290
39. Kniazeff J, Bessis AS, Maurel D, Ansanay H, Prezeau L, Pin JP 2004 Closed state of both binding domains of homodimeric mGlu receptors is required for full activity. Nat Struct Mol Biol 11:706-713
40. Ankersen M, Hansen TK, Ahnfelt-Ronne I, I, Kappelgaard AM 1999 Growth hormone secretagogues: recent advances and applications. Drug Discov Today 4:497-506
41. Feighner SD, Howard AD, Prendergast K, Palyha OC, Hreniuk DL, Nargund R, Underwood D, Tata JR, Dean DC, Tan CP, McKee KK, Woods JW, Patchett AA, Smith RG, Van Der Ploeg LH 1998 Structural requirements for the activation of the human growth hormone secretagogue receptor by peptide and nonpeptide secretagogues. Mol Endocrinol 12:137-145
42. Bodart V, Febbraio M, Demers A, McNicoll N, Pohankova P, Perreault A, Sejlitz T, Escher E, Silverstein RL, Lamontagne D, Ong H 2002 CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circ Res 90:844-849
43. Bach MA, Rockwood K, Zetterberg C, Thamsborg G, Hebert R, Devogelaer JP, Christiansen JS, Rizzoli R, Ochsner JL, Beisaw N, Gluck O, Yu L, Schwab T, Farrington J, Taylor AM, Ng J, Fuh V 2004 The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc 52:516-523
44. Holst B, Zoffmann S, Elling CE, Hjorth SA, Schwartz TW 1998 Steric hindrance mutagenesis versus alanine scan in mapping of ligand binding sites in the tachykinin NK1 receptor. Mol Pharm 53:166-175