Ghrelin, a 28-amino acid peptide, was recently identified from the stomach as the first endogenous ligand for growth hormone secretagogue receptors (previously known as orphan receptors). Ghrelin was discovered by ‘reverse pharmacology’. The acyl ghrelin peptide features a unique post-translational modification of O-n-octanoylation at serine 3, and is the only gastrointestinal signal that increases meal size. However, des-acyl ghrelin accounts for the major forms in the plasma. Most recently, obestatin, a novel 23-amino acid peptide, was derived from the mammalian preproghrelin gene, which also encodes ghrelin, by a bioinformatic approach. This at-the-cutting-edge review focuses on three ghrelin gene products: acyl ghrelin, des-acyl ghrelin, and the newly identified obestatin. Their updated orexigenic and anorexigenic effects on food intake, their signal transduction pathways from the periphery to the brain, as well as their roles in modulating gastrointestinal motility, and potential applications in the many fields of medicine such as eating disorders, obesity/anorexia-cachexia, and gastrointestinal dysmotility under different conditions, are critically addressed.

Keywords:
Acyl ghrelin, Des-acyl ghrelin, Obestatin, Food intake, Gastric emptying, Motility, Obesity
1.
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.
2.
Chen CY, Fujimiya M, Asakawa A, Lee SD, Inui A: Regulation of ingestive behavior, the upper gastrointestinal motility and gastric acid secretion by ghrelin in mammals. Curr Nutr Food Sci 2008;4:32–40.
3.
Gutierrez JA, Solenberg PJ, Perkins DR, Willency JA, Knierman MD, Jin Z, Witcher DR, Luo S, Onyia JE, Hale JE: Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci USA 2008;105:6320–6325.
4.
Garcia JM, Garcia-Touza M, Hijazi RA, Taffet G, Epner D, Mann D, Smith RG, Cunningham GR, Marcelli M: Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia. J Clin Endocrinol Metab 2005;90:2920–2926.
5.
Hosoda H, Kojima M, Matsuo H, Kangawa K: Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 2000;279:909–913.
6.
Yoshimoto A, Mori K, Sugawara A, Mukoyama M, Yahata K, Suganami T, Takaya K, Hosoda H, Kojima M, Kangawa K, Nakao K: Plasma ghrelin and desacyl ghrelin concentrations in renal failure. J Am Soc Nephrol 2002;13:2748–2752.
7.
Hosoda H, Kojima M, Matsuo H, Kangawa K: Purification and characterization of rat des-Gln14-ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem 2000;275:21995–22000.
8.
Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL: Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 2008;132:387–396.
9.
Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJ: Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 2005;310:996–999.
10.
Bedendi I, Alloatti G, Marcantoni A, Malan D, Catapano F, Ghé C, Deghenghi R, Ghigo E, Muccioli G: Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin. Eur J Pharmacol 2003;476:87–95.
11.
Caminos JE, Tena-Sempere M, Gaytán F, Sanchez-Criado JE, Barreiro ML, Nogueiras R, Casanueva FF, Aguilar E, Diéguez C: Expression of ghrelin in the cyclic and pregnant rat ovary. Endocrinology 2003;144:1594–1602.
12.
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.
13.
Brzozowski T, Konturek PC, Drozdowicz D, Konturek SJ, Pawlik M, Sliwowski Z, Pawlik WW, Hahn EG: Role of central and peripheral ghrelin in the mechanism of gastric mucosal defense. Inflammopharmacology 2005;13:45–62.
14.
Granata R, Settanni F, Gallo D, Trovato L, Biancone L, Cantaluppi V, Nano R, Annunziata M, Campiglia P, Arnoletti E, Ghè C, Volante M, Papotti M, Muccioli G, Ghigo E: Obestatin promotes survival of pancreatic β-cells and human islets and induces expression of genes involved in the regulation of β-cell mass and function. Diabetes 2008;57:967–979.
15.
Kapica M, Zabielska M, Puzio I, Jankowska A, Kato I, Kuwahara A, Zabielski R: Obestatin stimulates the secretion of pancreatic juice enzymes through a vagal pathway in anaesthetized rats: preliminary results. J Physiol Pharmacol 2007;58(suppl 3):123–130.
16.
Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujimiya M, Niijima A, Fujino MA, Kasuga M: Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 2001;120:337–345.
17.
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.
18.
Chen CY, Inui A, Asakawa A, Fujino K, Kato I, Chen CC, Ueno N, Fujimiya M: Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology 2005;129:8–25.
19.
Chen CY, Chao Y, Chang FY, Chien EJ, Lee SD, Doong ML: Intracisternal des-acyl ghrelin inhibits food intake and non-nutrient gastric emptying in conscious rats. Int J Mol Med 2005;16:695–699.
20.
Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, Kangawa K, Nakazato M: The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 2002;123:1120–1128.
21.
Solomon A, De Fanti BA, Martínez JA: The nucleus tractus solitari (NTS) participates in peripheral ghrelin glucostatic hunger signalling mediated by insulin. Neuropeptides 2006;40:169–175.
22.
Date Y, Shimbara T, Koda S, Toshinai K, Ida T, Murakami N, Miyazato M, Kokame K, Ishizuka Y, Ishida Y, Kageyama H, Shioda S, Kangawa K, Nakazato M: Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus. Cell Metab 2006;4:323–331.
23.
Gilg S, Lutz TA: The orexigenic effect of peripheral ghrelin differs between rats of different age and with different baseline food intake, and it may in part be mediated by the area postrema. Physiol Behav 2006;87:353–359.
24.
Hashimoto H, Fujihara H, Kawasaki M, Saito T, Shibata M, Otsubo H, Takei Y, Ueta Y: Centrally and peripherally administered ghrelin potently inhibits water intake in rats. Endocrinology 2007;148:1638–1647.
25.
le Roux CW, Neary NM, Halsey TJ, Small CJ, Martinez-Isla AM, Ghatei MA, Theodorou NA, Bloom SR: Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab 2005;90:4521–4524.
26.
Arnold M, Mura A, Langhans W, Geary N: Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat. J Neurosci 2006;26:11052–11060.
27.
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.
28.
Shaw AM, Irani BG, Moore MC, Haskell-Luevano C, Millard WJ: Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice. Peptides 2005;26:1720–1727.
29.
Chen HY, Trumbauer ME, Chen AS, Weingarth DT, Adams JR, Frazier EG, Shen Z, Marsh DJ, Feighner SD, Guan XM, Ye Z, Nargund RP, Smith RG, Van der Ploeg LH, Howard AD, MacNeil DJ, Qian S: Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 2004;145:2607–2612.
30.
López M, Lage R, Saha AK, Pérez-Tilve D, Vázquez MJ, Varela L, Sangiao-Alvarellos S, Tovar S, Raghay K, Rodríguez-Cuenca S, Deoliveira RM, Gastañeda T, Datta R, Dong JZ, Culler M, Sleeman MW, Alvarez CV, Gallego R, Lelliott CJ, Carling D, Tschöp MH, Diéguez C, Vidal-Puig A: Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab 2008;7:389–399.
31.
Kohno D, Sone H, Minokoshi Y, Yada T: Ghrelin raises [Ca2+]i via AMPK in hypothalamic arcuate nucleus NPY neurons. Biochem Biophys Res Commun 2008;366:388–392.
32.
Tschöp M, Smiley DL, Heiman ML: Ghrelin induces adiposity in rodents. Nature 2000;407:908–913.
33.
Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, Batterham RL, Taheri S, Stanley SA, Ghatei MA, Bloom SR: Ghrelin causes hyperphagia and obesity in rats. Diabetes 2001;50:2540–2547.
34.
Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, Castaneda TR, Muzzin P, Schürmann A, Szanto I, Tschöp MH, Rohner-Jeanrenaud F: Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 2006;116:1983–1993.
35.
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.
36.
Esler WP, Rudolph J, Claus TH, Tang W, Barucci N, Brown SE, Bullock W, Daly M, Decarr L, Li Y, Milardo L, Molstad D, Zhu J, Gardell SJ, Livingston JN, Sweet LJ: Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. Endocrinology 2007;148:5175–5185.
37.
Sun Y, Ahmed S, Smith RG: Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 2003;23:7973–7981.
38.
Wortley KE, del Rincon JP, Murray JD, Garcia K, Iida K, Thorner MO, Sleeman MW: Absence of ghrelin protects against early-onset obesity. J Clin Invest 2005;115:3573–3578.
39.
Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, Jones JE, Deysher AE, Waxman AR, White RD, Williams TD, Lachey JL, Seeley RJ, Lowell BB, Elmquist JK: Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest 2005;115:3564–3572.
40.
Pfluger PT, Kirchner H, Günnel S, Schrott B, Perez-Tilve D, Fu S, Benoit SC, Horvath T, Joost HG, Wortley KE, Sleeman MW, Tschöp MH: Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure. Am J Physiol Gastrointest Liver Physiol 2008;294:G610–G618.
41.
Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS: A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50:1714–1719.
42.
Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML: Circulating ghrelin levels are decreased in human obesity. Diabetes 2001;50:707–709.
43.
Zwirska-Korczala K, Konturek SJ, Sodowski M, Wylezol M, Kuka D, Sowa P, Adamczyk-Sowa M, Kukla M, Berdowska A, Rehfeld JF, Bielanski W, Brzozowski T: Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome. J Physiol Pharmacol 2007;58(suppl 1):13–35.
44.
Druce MR, Neary NM, Small CJ, Milton J, Monteiro M, Patterson M, Ghatei MA, Bloom SR: Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers. Int J Obes 2006;30:293–296.
45.
Levin F, Edholm T, Schmidt PT, Grybäck P, Jacobsson H, Degerblad M, Höybye C, Holst JJ, Rehfeld JF, Hellström PM, Näslund E: Ghrelin stimulates gastric emptying and hunger in normal-weight humans. J Clin Endocrinol Metab 2006;91:3296–3302.
46.
Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ: Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002;346:1623–1630.
47.
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.
48.
Haqq AM, Stadler DD, Rosenfeld RG, Pratt KL, Weigle DS, Frayo RS, LaFranchi SH, Cummings DE, Purnell JQ: Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome. J Clin Endocrinol Metab 2003;88:3573–3576.
49.
Asakawa A, Inui A, Fujimiya M, Sakamaki R, Shinfuku N, Ueta Y, Meguid MM, Kasuga M: Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut 2005;54:18–24.
50.
Pelleymounter MA, Joppa M, Ling N, Foster AC: Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 2004;25:659–666.
51.
Chen CY, Million M, Adelson DW, Martínez V, Rivier J, Taché Y: Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: role of CRF2. Br J Pharmacol 2002;136:237–247.
52.
Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, Date Y, Mondal MS, Shimbara T, Kawagoe T, Murakami N, Miyazato M, Kangawa K, Nakazato M: Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology 2006;147:2306–2314.
53.
Matsuda K, Miura T, Kaiya H, Maruyama K, Shimakura S, Uchiyama M, Kangawa K, Shioda S: Regulation of food intake by acyl and des-acyl ghrelins in the goldfish. Peptides 2006;27:2321–2325.
54.
Ariyasu H, Takaya K, Iwakura H, Hosoda H, Akamizu T, Arai Y, Kangawa K, Nakao K: Transgenic mice overexpressing des-acyl ghrelin show small phenotype. Endocrinology 2005;146:355–364.
55.
Soares JB, Leite-Moreira AF: Ghrelin, des-acyl ghrelin and obestatin: 3 pieces of the same puzzle. Peptides 2008;29:1255–1270.
56.
Kelley AE, Berridge KC: The neuroscience of natural rewards: relevance to addictive drugs. J Neurosci 2002;22:3306–3311.
57.
Naleid AM, Grace MK, Cummings DE, Levine AS: Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens. Peptides 2005;26:2274–2279.
58.
Malik S, McGlone F, Bedrossian D, Dagher A: Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab 2008;7:400–409.
59.
Jackson VR, Nothacker HP, Civelli O: GPR39 receptor expression in the mouse brain. Neuroreport 2006;17:813–816.
60.
McKee KK, Tan CP, Palyha OC, Liu J, Feighner SD, Hreniuk DL, Smith RG, Howard AD, Van der Ploeg LH: Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors. Genomics 1997;46:426–434.
61.
Lauwers E, Landuyt B, Arckens L, Schoofs L, Luyten W: Obestatin does not activate orphan G protein-coupled receptor GPR39. Biochem Biophys Res Commun 2006;351:21–25.
62.
Holst B, Egerod KL, Schild E, Vickers SP, Cheetham S, Gerlach LO, Storjohann L, Stidsen CE, Jones R, Beck-Sickinger AG, Schwartz TW: GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology 2007;148:13–20.
63.
Chartrel N, Alvear-Perez R, Leprince J, Iturrioz X, Reaux-Le Goazigo A, Audinot V, Chomarat P, Coge F, Nosjean O, Rodriguez M, Galizzi JP, Boutin JA, Vaudry H, Llorens-Cortes C: Comment on ‘obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake’. Science 2007;315:766c.
64.
Zhang JV, Klein C, Ren PG, Kass S, Donck LV, Moechars D, Hsueh AJ: Response to comment on ‘obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake’. Science 2007;315:766d.
65.
Zhang JV, Jahr H, Luo CW, Klein C, Van Kolen K, Ver Donck L, De A, Baart E, Li J, Moechars D, Hsueh AJ: Obestatin induction of early-response gene expression in gastrointestinal and adipose tissues and the mediatory role of G protein-coupled receptor, GPR39. Mol Endocrinol 2008;22:1464–1475.
66.
Bresciani E, Rapetti D, Donà F, Bulgarelli I, Tamiazzo L, Locatelli V, Torsello A: Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat. J Endocrinol Invest 2006;29:RC16–RC18.
67.
Zizzari P, Longchamps R, Epelbaum J, Bluet-Pajot MT: Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents. Endocrinology 2007;148:1648–1653.
68.
Sibilia V, Bresciani E, Lattuada N, Rapetti D, Locatelli V, De Luca V, Donà F, Netti C, Torsello A, Guidobono F: Intracerebroventricular acute and chronic administration of obestatin minimally affect food intake but not weight gain in the rat. J Endocrinol Invest 2006;29:RC31–RC34.
69.
Carlini VP, Schiöth HB, Debarioglio SR: Obestatin improves memory performance and causes anxiolytic effects in rats. Biochem Biophys Res Commun 2007;352:907–912.
70.
Green BD, Irwin N, Flatt PR: Direct and indirect effects of obestatin peptides on food intake and the regulation of glucose homeostasis and insulin secretion in mice. Peptides 2007;28:981–987.
71.
Lagaud GJ, Young A, Acena A, Morton MF, Barrett TD, Shankley NP: Obestatin reduces food intake and suppresses body weight gain in rodents. Biochem Biophys Res Commun 2007;357:264–269.
72.
Seoane LM, Al-Massadi O, Pazos Y, Pagotto U, Casanueva FF: Central obestatin administration does not modify either spontaneous or ghrelin-induced food intake in rats. J Endocrinol Invest 2006;29:RC13–RC15.
73.
Gourcerol G, Million M, Adelson DW, Wang Y, Wang L, Rivier J, St-Pierre DH, Taché Y: Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents. Peptides 2006;27:2811–2819.
74.
Nogueiras R, Pfluger P, Tovar S, Arnold M, Mitchell S, Morris A, Perez-Tilve D, Vázquez MJ, Wiedmer P, Castañeda TR, DiMarchi R, Tschöp M, Schurmann A, Joost HG, Williams LM, Langhans W, Diéguez C: Effects of obestatin on energy balance and growth hormone secretion in rodents. Endocrinology 2007;148:21–26.
75.
Yamamoto D, Ikeshita N, Daito R, Herningtyas EH, Toda K, Takahashi K, Iida K, Takahashi Y, Kaji H, Chihara K, Okimura Y: Neither intravenous nor intracerebroventricular administration of obestatin affects the secretion of GH, PRL, TSH and ACTH in rats. Regul Pept 2007;138:141–144.
76.
De Smet B, Thijs T, Peeters TL, Depoortere I: Effect of peripheral obestatin on gastric emptying and intestinal contractility in rodents. Neurogastroenterol Motil 2007;19:211–217.
77.
Gourcerol G, Coskun T, Craft LS, Mayer JP, Heiman ML, Wang L, Million M, St-Pierre DH, Taché Y: Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean or obese rodents. Obesity 2007;15:2643–2652.
78.
Vicennati V, Genghini S, De Iasio R, Pasqui F, Pagotto U, Pasquali R: Circulating obestatin levels and the ghrelin/obestatin ratio in obese women. Eur J Endocrinol 2007;157:295–301.
79.
Qi X, Li L, Yang G, Liu J, Li K, Tang Y, Liou H, Boden G: Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus. Clin Endocrinol 2007;66:593–597.
80.
Nakahara T, Harada T, Yasuhara D, Shimada N, Amitani H, Sakoguchi T, Kamiji MM, Asakawa A, Inui A: Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa. Biol Psychiatry 2008;64:252–255.
81.
Fujino K, Inui A, Asakawa A, Kihara N, Fujimura M, Fujimiya M: Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats. J Physiol 2003;550:227–240.
82.
Dornonville de la Cour C, Lindström E, Norlén P, Håkanson R: Ghrelin stimulates gastric emptying but is without effect on acid secretion and gastric endocrine cells. Regul Pept 2004;120:23–32.
83.
Levin F, Edholm T, Ehrström M, Wallin B, Schmidt PT, Kirchgessner AM, Hilsted LM, Hellström PM, Näslund E: Effect of peripherally administered ghrelin on gastric emptying and acid secretion in the rat. Regul Pept 2005;131:59–65.
84.
Chen CY, Doong ML, Chien EJ, Luo JC, Lu CL, Lin HC, Chang FY, Lee SD: Intracerebroventricular ghrelin enhances non-nutrient semiliquid gastric emptying in fasted conscious rats. Gastroenterol J Taiwan 2008;25:242–248.
85.
Tack J, Depoortere I, Bisschops R, Delporte C, Coulie B, Meulemans A, Janssens J, Peeters T: Influence of ghrelin on interdigestive gastrointestinal motility in humans. Gut 2006;55:327–333.
86.
Murray CD, Martin NM, Patterson M, Taylor SA, Ghatei MA, Kamm MA, Johnston C, Bloom SR, Emmanuel AV: Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study. Gut 2005;54:1693–1698.
87.
Binn M, Albert C, Gougeon A, Maerki H, Coulie B, Lemoyne M, Rabasa Lhoret R, Tomasetto C, Poitras P: Ghrelin gastrokinetic action in patients with neurogenic gastroparesis. Peptides 2006;27:1603–1606.
88.
Tack J, Depoortere I, Bisschops R, Verbeke K, Janssens J, Peeters T: Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment Pharmacol Ther 2005;22:847–853.
89.
Trudel L, Bouin M, Tomasetto C, Eberling P, St-Pierre S, Bannon P, L’Heureux MC, Poitras P: Two new peptides to improve post-operative gastric ileus in dog. Peptides 2003;24:531–534.
90.
Trudel L, Tomasetto C, Rio MC, Bouin M, Plourde V, Eberling P, Poitras P: Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat. Am J Physiol Gastrointest Liver Physiol 2002;282:G948–G952.
91.
Poitras P, Polvino WJ, Rocheleau B: Gastrokinetic effect of ghrelin analog RC-1139 in the rat: effect on post-operative and on morphine induced ileus. Peptides 2005;26:1598–1601.
92.
Venkova K, Fraser G, Hoveyda HR, Greenwood-Van Meerveld B: Prokinetic effects of a new ghrelin receptor agonist TZP-101 in a rat model of postoperative ileus. Dig Dis Sci 2007;52:2241–2248.
93.
Ataka K, Inui A, Asakawa A, Kato I, Fujimiya M: Obestatin inhibits motor activity in the antrum and duodenum in the fed state of conscious rats. Am J Physiol Gastrointest Liver Physiol 2008;294:G1210–G1218.
94.
Bassil AK, Häglund Y, Brown J, Rudholm T, Hellström PM, Näslund E, Lee K, Sanger GJ: Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract. Br J Pharmacol 2007;150:58–64.
95.
Zhao CM, Furnes MW, Stenström B, Kulseng B, Chen D: Characterization of obestatin-and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: an immunohistochemical and electron-microscopic study. Cell Tissue Res 2008;331:578–587.
96.
Chen CY, Chien EJ, Chang FY, Lu CL, Luo JC, Lee SD: Impacts of peripheral obestatin on colonic motility and secretion in conscious fed rats. Peptides 2008;29:1603–1608.
97.
Samson WK, White MM, Price C, Ferguson AV: Obestatin acts in brain to inhibit thirst. Am J Physiol Regul Integr Comp Physiol 2007;292:R637–R643.
98.
Szentirmai E, Krueger JM: Obestatin alters sleep in rats. Neurosci Lett 2006;404:222–226.
99.
Dun SL, Brailoiu GC, Brailoiu E, Yang J, Chang JK, Dun NJ: Distribution and biological activity of obestatin in the rat. J Endocrinol 2006;191:481–489.
100.
Camiña JP, Campos JF, Caminos JE, Dieguez C, Casanueva FF: Obestatin-mediated proliferation of human retinal pigment epithelial cells: regulatory mechanisms. J Cell Physiol 2007;211:1–9.
© 2008 S. Karger AG, Basel
2008
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.