A novel growth hormone secretagogue-1a receptor antagonist that blocks ghrelin-induced growth hormone secretion but induces increased body weight gain

Neuroendocrinology

Volumn 81, Issue 5, 2005, Pages 339-349

  Halem, Heather A ^a   Taylor, John E ^a   Dong, Jesse Z ^a   Shen, Yeelana ^a   Datta, Rakesh ^a   Abizaid, Alfonso ^b   Diano, Sabrina ^b   Horvath, Tamas L ^b   Culler, Michael D ^a  

^a IPSEN   (France)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Dorsal medial hypothalamus; Food intake; Fos; Ghrelin; Growth hormone; Growth hormone secretagogue antagonists; Obesity

Indexed keywords

BIM 28163; GHRELIN; GROWTH HORMONE; GROWTH HORMONE SECRETAGOGUE 1A RECEPTOR ANTAGONIST; PROTEIN FOS; RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARCUATE NUCLEUS; ARTICLE; CONTROLLED STUDY; FOOD INTAKE; HORMONE RELEASE; HYPOTHALAMUS; IMMUNOREACTIVITY; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; UPREGULATION; WEIGHT GAIN;

ANIMALS; AREA UNDER CURVE; BEHAVIOR, ANIMAL; BINDING, COMPETITIVE; BODY WEIGHT; BRAIN; CELL COUNT; CHO CELLS; CRICETINAE; CRICETULUS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; FEEDING BEHAVIOR; GROWTH HORMONE; HUMANS; IMMUNOHISTOCHEMISTRY; IODINE ISOTOPES; MALE; ONCOGENE PROTEINS V-FOS; PEPTIDE HORMONES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, G-PROTEIN-COUPLED; TIME FACTORS;

EID: 27344437877     PISSN: 00283835     EISSN: None     Source Type: Journal    
DOI: 10.1159/000088796     Document Type: Article

References (39)

1. Fehrentz JA, Martinez J, Boeglin D, Guerlavais V, Deghenghi R: Growth hormone secretagogues: past, present and future. IDrugs 2002;5:804-814.
2. 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, Patchett AA, Nargund R, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LH: A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996;273:974-977.
3. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-660.
4. Bowers CY: Unnatural growth hormone-releasing peptide begets natural ghrelin. J Clin Endocrinol Metab 2001;86:1464-1469.
5. Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, VanderPloeg LHT, Howard AS: Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 1997;48:23-29.
6. Mitchell V, Bouret S, Beauvillain JC, Schilling A, Perret M, Kordon C, Epelbaum J: Comparative distribution of mRNA encoding the growth hormone secretagogue-receptor (GHS-R) in Microcebus murinus (Primate, lemurian) and rat forebrain and pituitary. J Comp Neurol 2001;15:469-489.
7. Tschop M, Smiley DL, Heiman ML: Ghrelin induces adiposity in rodents. Nature 2000;407:908-913.
8. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S: A role for ghrelin in the central regulation of feeding. Nature 2001;409:194-198.
9. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR: Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001;86:5992-5995.
10. Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates, ed 4. New York, Academic Press, 1998.
11. Ghigo E, Arvat E, Giordano R, Broglio F, Gianotti L, Maccario M, Bisi G, Graziani A, Papotti M, Muccioli G, Deghenghi R, Camanni F: Biologic activities of growth hormone secretagogues in humans. Endocrine 2001;14:87-93.
12. Tannenbaum GS, Epelbaum J, Bowers CY: Interrelationship between the novel peptide ghrelin and somatostatin/growth hormone-releasing hormone in regulation of pulsatile growth hormone secretion. Endocrinology 2003;144:967-974.
13. Horvath TL, Castaneda T, Tang-Christensen M, Pagotto U, Tschop MH: Ghrelin as a potential anti-obesity target. Curr Pharm Des 2003;9:1383-1395.
14. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR: The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000;141:4325-4328.
15. Horvath TL, Diano S, Sotonyi P, Heiman M, Tschop M: Minireview: ghrelin and the regulation of energy balance - a hypothalamic perspective. Endocrinology 2001; 142: 4163-4169.
16. Bluet-Pajot MT, Epelbaum J, Gourdji D, Hammond C, Kordon C: Hypothalamic and hypophyseal regulation of growth hormone secretion. Cell Mol Neurobiol 1998;18:101-123.
17. Hewson AK, Tung LY, Connell DW, Tookman L, Dickson SL: The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic. Diabetes 2002;51:3412-3419.
18. Bellinger LL, Bernardis LL: The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation: lessons learned from lesioning studies. Physiol Behav 2002;76:431-442.
19. Snyder SH: Opiate receptors and beyond: 30 years of neural signaling research. Neuropharmacology 2004;47(suppl 1):274-285.
20. Reisine T, Bell GI: Molecular properties of somatostatin receptors. Neuroscience 1995;67:777-790.
21. Voisey J, Carroll L, van Daal A: Melanocortins and their receptors and antagonists. Curr Drug Targets 2003;4:586-597.
22. Fujita Y, Tsuda Y, Li T, Motoyama T, Takahashi M, Shimizu Y, Yokoi T, Sasaki Y, Ambo A, Kita A, Jinsmaa Y, Bryant SD, Lazarus LH, Okada Y: Development of potent bifunctional endomorphin-2 analogues with mixed mu-/delta-opioid agonist and delta-opioid antagonist properties. J Med Chem 2004;47:3591-3599.
23. Tulipano G, Soldi D, Bagnasco M, Culler MD, Taylor JE, Cocchi D, Giustina A: Characterization of new selective somatostatin receptor subtype-2 (sst2) antagonist, BIM-23627 and BIM-23454. Effects of BIM-23627 on GH release in anesthetized male rats after short-term high dose dexamethasone treatment. Endocrinology 2002;143:1218-1224.
24. Schioth HB, Muceniece R, Mutulis F, Bouifrouri AA, Mutule I, Wikberg JE: Further pharmacological characterization of the selective melanocortin 4 receptor antagonist HS014: comparison with SHU9119. Neuropeptide 1999;33:191-196.
25. Thompson NM, Gill DA, Davies R, Loveridge N, Houston PA, Robinson IC, Wells T: Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 2004;145:234-242.
26. Torsello A, Luoni M, Schweiger F, Grilli R, Guidi M, Bresciani E, Deghenghi R, Muller EE, Locatelli V: Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release. Eur J Pharmacol 1998;360:123-129.
27. Torsello A, Locatelli V, Melis MR, Succu S, Spano MS, Deghenghi R, Muller EE, Argiolas A: Differential orexigenic effects of hexarelin and its analogs in the rat hypothalamus: indication for multiple growth hormone secretagogue receptor subtypes. Neuroendocrinology 2000;72:327-332.
28. Lall S, Tung LY, Ohlsson C, Jansson JO, Dickson SL: Growth hormone (GH)-independent stimulation of adiposity by GH secretagogue. Biochem Biophys Res Commun 2001;280:132-138.
29. Tschop M, Statnick MA, Suter TM, Heiman ML: GH-releasing peptide-2 increases fat mass in mice lacking NPY: Indication for a crucial mediating role of hypothalamic agouti-related protein. Endocrinology 2002;143:558-568.
30. Asakawa A, Inui A, Kaga T, Katsuura G, Fujimiya M, Fujino MA, Kasuga M: Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003;52:947-952.
31. Holst JJ, Knuhtsen S, Orskov C, Skak-Nielsen T, Poulsen SS, Nielsen OV: GRP-producing nerves control antral somatostatin and gastrin secretion in pigs. Am J Physiol 1987;253:G767-G774.
32. Woll PJ, Rozengurt E: [D-Arg1,D-Phe5,D-Trp7,9.Leu11] substance P, a potent bombesin antagonist in murine Swiss 3T3 cells, inhibits the growth of human small cell lung cancer cells in vitro. Proc Natl Acad Sci USA 1988;85:1859-1863.
33. Shuto Y, Shibasaki T, Otagiri A, Kuriyama H, Ohata H, Tamura H, Kamegai J, Sugihara H, Oikawa S, Wakabayashi I: Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity. J Clin Invest 2002;109:1429-1436.
34. Riediger T, Traebert M, Schmid HA, Scheel C, Lutz TA, Scharrer E: Site-specific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus. Neurosci Lett 2003;341:151-155.
35. 2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes 2003;52:948-956.
36. Bagnasco M, Tulipano G, Melis MR, Argiolas A, Cocchi D, Muller EE: Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting. Regul Pept 2003;111:161-167.
37. Muccioli G, Ghe C, Ghigo MC, Papotti M, Arvat E, Boghen MF, Nilsson MH, Deghenghi R, Ong H, Ghigo E: Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland. J Endocrinol 1998;157:99-106.
38. Yuxiang S, Wang P, Zheng H, Smith RG: Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci USA 2004;101:4679-4684.
39. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS: Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med 2002;8:643-644.