Recovery research fieldbook Evidence, not treatment advice
Recovery archive

Published recovery field note

Introduction to Ghrelin receptor

1. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S et al.. (2001) Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab, 86 (10): 4753-8. [PMID:11600536] 2. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, Malan D, Baj G, Granata R, Broglio F et al.. (2002) Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol, 159 (6): 1029-37. [PMID:12486113] 3. Bennett KA, Langmead CJ, Wise A, Milligan G. (2009) Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Galpha(o1) by the Ghrelin receptor. Mol Pharmacol, 76 (4): 802-11. [PMID:19625579] 4. Cassoni P, Ghé C, Marrocco T, Tarabra E, Allia E, Catapano F, Deghenghi R, Ghigo E, Papotti

Context first

Study findings do not automatically establish clinical benefit, safety, dosing, or suitability for an individual.

1. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S et al.. (2001) Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab, 86 (10): 4753-8. [PMID:11600536]

2. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, Malan D, Baj G, Granata R, Broglio F et al.. (2002) Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol, 159 (6): 1029-37. [PMID:12486113]

3. Bennett KA, Langmead CJ, Wise A, Milligan G. (2009) Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Galpha(o1) by the Ghrelin receptor. Mol Pharmacol, 76 (4): 802-11. [PMID:19625579]

4. Cassoni P, Ghé C, Marrocco T, Tarabra E, Allia E, Catapano F, Deghenghi R, Ghigo E, Papotti M, Muccioli G. (2004) Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines. Eur J Endocrinol, 150 (2): 173-84. [PMID:14763915]

5. Cassoni P, Papotti M, Ghè C, Catapano F, Sapino A, Graziani A, Deghenghi R, Reissmann T, Ghigo E, Muccioli G. (2001) Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab, 86 (4): 1738-45. [PMID:11297611]

6. Chen CY, Tsai CY. (2012) Ghrelin and motilin in the gastrointestinal system. Curr Pharm Des, 18 (31): 4755-65. [PMID:22632857]

7. Chu KM, Chow KB, Leung PK, Lau PN, Chan CB, Cheng CH, Wise H. (2007) Over-expression of the truncated ghrelin receptor polypeptide attenuates the constitutive activation of phosphatidylinositol-specific phospholipase C by ghrelin receptors but has no effect on ghrelin-stimulated extracellular signal-regulated kinase 1/2 activity. Int J Biochem Cell Biol, 39 (4): 752-64. [PMID:17169600]

8. Cummings DE, Foster-Schubert KE, Overduin J. (2005) Ghrelin and energy balance: focus on current controversies. Curr Drug Targets, 6 (2): 153-69. [PMID:15777186]

9. Damian M, Marie J, Leyris JP, Fehrentz JA, Verdié P, Martinez J, Banères JL, Mary S. (2012) High constitutive activity is an intrinsic feature of ghrelin receptor protein: a study with a functional monomeric GHS-R1a receptor reconstituted in lipid discs. J Biol Chem, 287 (6): 3630-41. [PMID:22117076]

10. Dash PK, Karl KA, Colicos MA, Prywes R, Kandel ER. (1991) cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase. Proc Natl Acad Sci USA, 88 (11): 5061-5. [PMID:1647024]

11. Davenport AP, Bonner TI, Foord SM, Harmar AJ, Neubig RR, Pin JP, Spedding M, Kojima M, Kangawa K. (2005) International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Pharmacol Rev, 57 (4): 541-6. [PMID:16382107]

12. Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E. (2011) The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol, 340 (1): 80-7. [PMID:21354264]

13. Feighner SD, Howard AD, Prendergast K, Palyha OC, Hreniuk DL, Nargund R, Underwood D, Tata JR, Dean DC, Tan CP et al.. (1998) Structural requirements for the activation of the human growth hormone secretagogue receptor by peptide and nonpeptide secretagogues. Mol Endocrinol, 12 (1): 137-45. [PMID:9440817]

14. Gozé C, Bergé G, M'Kadmi C, Floquet N, Gagne D, Galleyrand JC, Fehrentz JA, Martinez J. (2010) Involvement of tryptophan W276 and of two surrounding amino acid residues in the high constitutive activity of the ghrelin receptor GHS-R1a. Eur J Pharmacol, 643 (2-3): 153-61. [PMID:20599926]

15. Gualillo O, Caminos J, Blanco M, Garcìa-Caballero T, Kojima M, Kangawa K, Dieguez C, Casanueva F. (2001) Ghrelin, a novel placental-derived hormone. Endocrinology, 142 (2): 788-94. [PMID:11159851]

16. Holliday ND, Holst B, Rodionova EA, Schwartz TW, Cox HM. (2007) Importance of constitutive activity and arrestin-independent mechanisms for intracellular trafficking of the ghrelin receptor. Mol Endocrinol, 21 (12): 3100-12. [PMID:17717076]

17. Holst B, Cygankiewicz A, Jensen TH, Ankersen M, Schwartz TW. (2003) High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist. Mol Endocrinol, 17 (11): 2201-10. [PMID:12907757]

18. Holst B, Frimurer TM, Mokrosinski J, Halkjaer T, Cullberg KB, Underwood CR, Schwartz TW. (2009) Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor. Mol Pharmacol, 75 (1): 44-59. [PMID:18923064]

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 (51): 53806-17. [PMID:15383539]

20. Holst B, Lang M, Brandt E, Bach A, Howard A, Frimurer TM, Beck-Sickinger A, Schwartz TW. (2006) Ghrelin receptor inverse agonists: identification of an active peptide core and its interaction epitopes on the receptor. Mol Pharmacol, 70 (3): 936-46. [PMID:16798937]

21. Holst B, Mokrosinski J, Lang M, Brandt E, Nygaard R, Frimurer TM, Beck-Sickinger AG, Schwartz TW. (2007) Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism. J Biol Chem, 282 (21): 15799-811. [PMID:17371869]

22. Holst B, Schwartz TW. (2004) Constitutive ghrelin receptor activity as a signaling set-point in appetite regulation. Trends Pharmacol Sci, 25 (3): 113-7. [PMID:15058279]

23. Hosoda H, Kojima M, Matsuo H, Kangawa K. (2000) Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem, 275 (29): 21995-2000. [PMID:10801861]

24. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J et al.. (1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Science, 273 (5277): 974-7. [PMID:8688086]

25. Jiang H, Betancourt L, Smith RG. (2006) Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol Endocrinol, 20 (8): 1772-85. [PMID:16601073]

26. Katugampola SD, Pallikaros Z, Davenport AP. (2001) [125I-His(9)]-ghrelin, a novel radioligand for localizing GHS orphan receptors in human and rat tissue: up-regulation of receptors with athersclerosis. Br J Pharmacol, 134 (1): 143-9. [PMID:11522606]

27. Kern A, Albarran-Zeckler R, Walsh HE, Smith RG. (2012) Apo-ghrelin receptor forms heteromers with DRD2 in hypothalamic neurons and is essential for anorexigenic effects of DRD2 agonism. Neuron, 73 (2): 317-32. [PMID:22284186]

28. Kleinz MJ, Kuc RE, Maguire JJ, Davenport AP. Endogenous vasodilator ghrelin and its growth hormone secretagogue receptor 1a (GHS-R1a) immunocytochemically localize to endothelial cells within the human vasculature. Accessed on 05/05/2015. Modified on 05/05/2015. BPS pA2 online abstracts, http://www.pa2online.org/scripts/relatedVol1Issue3.asp

29. 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 (6762): 656-60. [PMID:10604470]

30. Kojima M, Kangawa K. (2005) Ghrelin: structure and function. Physiol Rev, 85 (2): 495-522. [PMID:15788704]

31. Korbonits M, Kojima M, Kangawa K, Grossman AB. (2001) Presence of ghrelin in normal and adenomatous human pituitary. Endocrine, 14 (1): 101-4. [PMID:11322490]

32. Malcolm JA, Sutherland DC. (1991) HIV and nutrition. Lancet, 338 (8769): 760. [PMID:1679893]

33. Mary S, Damian M, Louet M, Floquet N, Fehrentz JA, Marie J, Martinez J, Banères JL. (2012) Ligands and signaling proteins govern the conformational landscape explored by a G protein-coupled receptor. Proc Natl Acad Sci USA, 109 (21): 8304-9. [PMID:22573814]

34. Mokrosiński J, Frimurer TM, Sivertsen B, Schwartz TW, Holst B. (2012) Modulation of constitutive activity and signaling bias of the ghrelin receptor by conformational constraint in the second extracellular loop. J Biol Chem, 287 (40): 33488-502. [PMID:22846991]

35. Mousseaux D, Le Gallic L, Ryan J, Oiry C, Gagne D, Fehrentz JA, Galleyrand JC, Martinez J. (2006) Regulation of ERK1/2 activity by ghrelin-activated growth hormone secretagogue receptor 1A involves a PLC/PKCvarepsilon pathway. Br J Pharmacol, 148 (3): 350-65. [PMID:16582936]

36. Nagaya N, Kangawa K. (2003) Ghrelin improves left ventricular dysfunction and cardiac cachexia in heart failure. Curr Opin Pharmacol, 3 (2): 146-51. [PMID:12681236]

37. Nagaya N, Kangawa K. (2003) Ghrelin, a novel growth hormone-releasing peptide, in the treatment of chronic heart failure. Regul Pept, 114 (2-3): 71-7. [PMID:12832093]

38. Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K. (2001) Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol, 280 (5): R1483-7. [PMID:11294772]

39. Nagaya N, Miyatake K, Uematsu M, Oya H, Shimizu W, Hosoda H, Kojima M, Nakanishi N, Mori H, Kangawa K. (2001) Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab, 86 (12): 5854-9. [PMID:11739451]

40. Nagaya N, Uematsu M, Kojima M, Ikeda Y, Yoshihara F, Shimizu W, Hosoda H, Hirota Y, Ishida H, Mori H et al.. (2001) Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation, 104 (12): 1430-5. [PMID:11560861]

41. Okumura H, Nagaya N, Enomoto M, Nakagawa E, Oya H, Kangawa K. (2002) Vasodilatory effect of ghrelin, an endogenous peptide from the stomach. J Cardiovasc Pharmacol, 39: 779-783. [PMID:12021570]

42. Palus S, Schur R, Akashi YJ, Bockmeyer B, Datta R, Halem H, Dong J, Culler MD, Adams V, Anker SD et al.. (2011) Ghrelin and its analogues, BIM-28131 and BIM-28125, improve body weight and regulate the expression of MuRF-1 and MAFbx in a rat heart failure model. PLoS ONE, 6 (11): e26865. [PMID:22102869]

43. Poitras P, Peeters TL. (2008) Motilin. Curr Opin Endocrinol Diabetes Obes, 15 (1): 54-7. [PMID:18185063]

44. Rediger A, Piechowski CL, Habegger K, Grüters A, Krude H, Tschöp MH, Kleinau G, Biebermann H. (2012) MC4R dimerization in the paraventricular nucleus and GHSR/MC3R heterodimerization in the arcuate nucleus: is there relevance for body weight regulation?. Neuroendocrinology, 95 (4): 277-88. [PMID:22327910]

45. Rudolph J, Esler WP, O'connor S, Coish PD, Wickens PL, Brands M, Bierer DE, Bloomquist BT, Bondar G, Chen L et al.. (2007) Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. J Med Chem, 50 (21): 5202-16. [PMID:17887659]

46. Schellekens H, van Oeffelen WE, Dinan TG, Cryan JF. (2013) Promiscuous dimerization of the growth hormone secretagogue receptor (GHS-R1a) attenuates ghrelin-mediated signaling. J Biol Chem, 288 (1): 181-91. [PMID:23161547]

47. Sivertsen B, Holliday N, Madsen AN, Holst B. (2013) Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor. Br J Pharmacol, 170 (7): 1349-62. [PMID:24032557]

48. Sivertsen B, Lang M, Frimurer TM, Holliday ND, Bach A, Els S, Engelstoft MS, Petersen PS, Madsen AN, Schwartz TW et al.. (2011) Unique interaction pattern for a functionally biased ghrelin receptor agonist. J Biol Chem, 286 (23): 20845-60. [PMID:21402696]

49. Tsubota Y, Owada-Makabe K, Yukawa K, Maeda M. (2005) Hypotensive effect of des-acyl ghrelin at nucleus tractus solitarii of rat. Neuroreport, 16 (2): 163-6. [PMID:15671869]

50. van der Lely AJ, Tschöp M, Heiman ML, Ghigo E. (2004) Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev, 25 (3): 426-57. [PMID:15180951]

51. Wierup N, Svensson H, Mulder H, Sundler F. (2002) The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept, 107 (1-3): 63-9. [PMID:12137967]

52. Wiley KE, Davenport AP. (2002) Comparison of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1. Br J Pharmacol, 136 (8): 1146-52. [PMID:12163347]

53. Xin Z, Serby MD, Zhao H, Kosogof C, Szczepankiewicz BG, Liu M, Liu B, Hutchins CW, Sarris KA, Hoff ED et al.. (2006) Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists. J Med Chem, 49 (15): 4459-69. [PMID:16854051]

Connected topics

Follow this recovery question