Centrally Administered Neuromedin S Inhibits Feeding Behavior and Gastroduodenal Motility in Mice

Abstract

Neuromedin S (NMS) was recently identified as an endogenous ligand for the FM-4/TGR-1 receptor in the rat hypothalamus. No previous studies have examined the effect of NMS on gut motility. We examined the effects of intracerebroventricular administration of NMS on food intake in food-deprived and free-feeding mice, and on gastroduodenal motility by using a manometric method, and gastric emptying in mice. We found that NMS decreased food intake and the gastric emptying rate. It also disrupted the motor activity in the antrum and duodenum of conscious food-deprived mice. These results suggest that NMS influences gut motility as well as feeding behavior.

neuromedin S - gastroduodenal motility - gastric emptying - feeding behavior - mice

References

• 1 Mori K, Miyazato M, Ida T, Murakami N, Serino R, Ueta Y, Kojima M, Kangawa K. Identification of neuromedin S and its possible role in the mammalian circadian oscillator system.  EMBO J. 2005;  24 325-335
• 2 Howard AD, Wang R, Pong SS, Mellin TN, Strack A, Guan XM, Zeng Z, Williams Jr DL, Feighner SD, Nunes CN, Murphy B, Stair JN, Yu H, Jiang Q, Clements MK, Tan CP, McKee KK, Hreniuk DL, McDonald TP, Lynch KR, Evans JF, Austin CP, Caskey CT, Van der Ploeg LH, Liu Q. Identification of receptors for neuromedin U and its role in feeding.  Nature. 2000;  406 70-74
• 3 Shan L, Qiao X, Crona JH, Behan J, Wang S, Laz T, Bayne M, Gustafson EL, Monsma Jr FJ, Hedrick JA. Identification of a novel neuromedin U receptor subtype expressed in the central nervous system.  J Biol Chem. 2000;  275 39482-39486
• 4 Raddatz R, Wilson AE, Artymyshyn R, Bonini JA, Borowsky B, Boteju LW, Zhou S, Kouranova EV, Nagorny R, Guevarra MS, Dai M, Lerman GS, Vaysse PJ, Branchek TA, Gerald C, Forray C, Adham N. Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system.  J Biol Chem. 2000;  275 32452-32459
• 5 Miyazato M, Mori K, Ida T, Kojima M, Murakami N, Kangawa K. Identification and functional analysis of a novel ligand for G protein-coupled receptor.  Neuromedin S. Regul Pept. 2008;  145 37-41
• 6 Fujii R, Hosoya M, Fukusumi S, Kawamata Y, Habata Y, Hinuma S, Onda H, Nishimura O, Fujino M. Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3.  J Biol Chem. 2000;  275 21068-21074
• 7 Hosoya M, Moriya T, Kawamata Y, Ohkubo S, Fujii R, Matsui H, Shintani Y, Fukusumi S, Habata Y, Hinuma S, Onda H, Nishimura O, Fujino M. Identification and functional characterization of a novel subtype of neuromedin U receptor.  J Biol Chem. 2000;  275 29528-29532
• 8 Rucinski M, Ziolkowska A, Neri G, Trejter M, Zemleduch T, Tyczewska M, Nussdorfer GG, Malendowicz LK. Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat.  Int J Mol Med. 2007;  20 255-259
• 9 Trejter M, Neri G, Rucinski M, Majchrzak M, Nussdorfer GG, Malendowicz LK. Neuromedin-U stimulates enucleation-induced adrenocortical regeneration in the rat.  Int J Mol Med. 2008;  21 683-687
• 10 Nakazato M, Hanada R, Murakami N, Date Y, Mondal MS, Kojima M, Yoshimatsu H, Kangawa K, Matsukura S. Central effects of neuromedin U in the regulation of energy homeostasis.  Biochem Biophys Res Commun. 2000;  277 191-194
• 11 Bechtold DA, Ivanov TR, Luckman SM. Appetite-modifying actions of pro-neuromedin U-derived peptides.  Am J Physiol Endocrinol Metab. 2009;  297 545-551
• 12 Kojima M, Haruno R, Nakazato M, Date Y, Murakami N, Hanada R, Matsuo H, Kangawa K. Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3).  Biochem Biophys Res Commun. 2000;  276 435-438
• 13 Wren AM, Small CJ, Abbott CR, Jethwa PH, Kennedy AR, Murphy KG, Stanley SA, Zollner AN, Ghatei MA, Bloom SR. Hypothalamic actions of neuromedin U.  Endocrinology. 2002;  143 4227-4234
• 14 Reppert SM, Weaver DR. Molecular analysis of mammalian circadian rhythms.  Annu Rev Physiol. 2001;  63 647-676
• 15 Reppert SM, Weaver DR. Coordination of circadian timing in mammals.  Nature. 2002;  418 935-941
• 16 Kreier F, Yilmaz A, Kalsbeek A, Romijn JA, Sauerwein HP, Fliers E, Buijs RM. Hypothesis: Shifting the equilibrium from activity to food leads to autonomic unbalance and the metabolic syndrome.  Diabetes. 2003;  52 2652-2656
• 17 La Fleur SE, Kalsbeek A, Wortel J, Fekkes ML, Buijs RM. A daily rhythm in glucose tolerance A role for the suprachiasmatic nucleus.  Diabetes. 2001;  50 1237-1243
• 18 Ida T, Mori K, Miyazato M, Egi Y, Abe S, Nakahara K, Nishihara M, Kangawa K, Murakami N. Neuromedin s is a novel anorexigenic hormone.  Endocrinology. 2005;  146 4217-4223
• 19 Jászberényi M, Bagosi Z, Thurzó B, Földesi I, Telegdy G. Endcrine and behavioral effects of neuromedin S.  Horm Behav. 2007;  52 631-639
• 20 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
• 21 Taksande BG, Kotagale NR, Tripathi SJ, Ugale RR, Chopde CT. Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine.  Neuropharmacology. 2009;  57 415-424
• 22 Prieur X, Tung YC, Griffin JL, Farooqi IS, O’Rahilly S, Coll AP. Leptin regulates peripheral lipid metabolism primarily through central effects on food intake.  Endocrinology. 2008;  149 5432-5439
• 23 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
• 24 Yayou K, Kitagawa S, Itoh S, Kasuya E, Sutoh M. Effects of intracerebroventricular administration of neuromedin U or neuromedin S in steers.  Gen Com Endocrinol. 2009;  163 324-328
• 25 Peier A, Kosinski J, Cox-York K, Qian Y, Desai K, Feng Y, Trivedi P, Hastings N, Marsh DJ. The antiobesity effects of centrally administered neuromedin U and neuromedin S are mediated predominantly by the neuromedin U receptor 2 (NMUR2).  Endocrinology. 2009;  150 3101-3109
• 26 Fujimiya M, Itoh E, Kihara N, Yamamoto I, Fujimura M, Inui A. Neuropeptide Y induces fasted pattern of duodenal motility via Y2 receptors in conscious fed rats.  Am J Physiol Gastrointest Liver Physiol. 2000;  278 32-38
• 27 Fujino K, Inui A, Asakawa A, Kihara N, Fujimura M, Fujimiya M. Ghrelin induces fasted motor activity of the gastrointestional tract in conscious fed rats.  J Physiol. 2003;  550 227-240
• 28 Kihara N, Fujimura M, Yamamoto I, Itoh E, Inui A, Fujimiya M. Effects of central and peripheral urocortin on fed and fasted gastroduodenal motor activity in conscious rats.  Am J Physiol Gastrointest Liver Physiol. 2001;  280 406-419
• 29 Smedh U, Uvnäs-Moberg K, Grill HJ, Kaplan JM. Fourth ventricular injection of corticotropin-releasing factor and gastric emptying of glucose during gastric fill.  Am J Physiol Gastrointest Liver Physiol. 1995;  269 1000-1003
• 30 Spina M, Merlo-Pich E, Chan RK, Basso AM, Rivier J, Vale W, Koob GF. Appetite-suppressing effects of urocortin, a CRF-related neuropeptide.  Science. 1996;  273 1561-1564
• 31 Poitras P, Tassé D, Laprise P. Stimulation of motilin release by bombesin in dogs.  Am J Physiol Gastrointest Liver Physiol. 1983;  245 249-256
• 32 Rodríguez-Membrilla A, Martínez V, Vergara P. Peripheral and central cholecystokinin receptors regulate postprandial intestinal motility in the rat.  J Pharmacol Exp Ther. 1996;  275 486-493
• 33 Tanaka R, Inui A, Asakawa A, Atsuchi K, Ataka K, Fujimiya M. New method of manometric measurement of gastroduodenal motility in conscious mice: Effects of ghrelin and Y2 depletion.  Am J Physiol Gastrointest Liver Physiol. 2009;  297 G1028-G1034

Correspondence