Neuromedin S: Discovery and Functions

Chapter
First Online:
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 46)

Abstract

Neuromedin S, a novel neuropeptide of 36 amino acids, was isolated from rat brain as an endogenous ligand for the orphan G protein-coupled receptors FM-3/GPR66 and FM-4/TGR-1, identified to date as type-1 and type-2 neuromedin U (NMU) receptors, respectively. The peptide was designated neuromedin S (NMS) because it is specifically expressed in the suprachiasmatic nucleus of the hypothalamus. NMS is structurally related to NMU; these peptides share a C-terminal core structure. In this review, we will outline the recent discoveries regarding the structure, cognate receptors, distribution, and possible physiological functions of NMS.

Keywords

Circadian Rhythm Vasoactive Intestinal Polypeptide Luteinizing Hormone Release GPR66 mRNA Orphan GPCRs 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brown DR, Quito FL (1988) Neuromedin U octapeptide alters ion transport in porcine jejunum. Eur J Pharmacol 155:159–162 PubMedCrossRefGoogle Scholar
  2. Chen T, Zhou M, Walker B, Harriot P, Mori K, Miyazato M, Kangawa K, Shaw C (2006) Structural and functional analogs of the novel mammalian neuropeptide, neuromedin S (NmS), in the dermal venoms of Eurasian bombinid toads. Biochem Biophys Res Commun 345:377–384 PubMedCrossRefGoogle Scholar
  3. Civelli O (1998) Functional genomics: the search for novel neurotransmitters and neuropeptides. FEBS Lett 430:55–58 PubMedCrossRefGoogle Scholar
  4. Civelli O, Saito Y, Wang Z, Nothacker HP, Reinscheid RK (2006) Orphan GPCRS and their ligands. Pharmacol Ther 110:525–532 PubMedCrossRefGoogle Scholar
  5. Fujii R, Hosoya M, Fukusumi S, Kawamata Y, Habata Y, Hinuma S, Onda H, Nishimura O, Fujino M (2000) Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3. J Biol Chem 275:21068–21074 PubMedCrossRefGoogle Scholar
  6. Graham ES, Turnbull Y, Fotheringham P, Nilaweera K, Mercer JG, Morgan PJ, Barrett P (2003) Neuromedin U and neuromedin U receptor-2 expression in the mouse and rat hypothalamus: effects of nutritional status. J Neurochem 87:1165–1173 PubMedCrossRefGoogle Scholar
  7. Hanada R, Nakazato M, Murakami N, Sakihara S, Yoshimatsu H, Toshinai K, Hanada T, Suda T, Kangawa K, Matsukura S (2001) A role for neuromedin U in stress response. Biochem Biophys Res Commun 289:225–228 PubMedCrossRefGoogle Scholar
  8. Hanada R, Teranishi H, Pearson JT, Kurokawa M, Hosoda H, Fukushima N, Fukue Y, Serino R, Fujihara H, Ueta Y, Ikawa M, Okabe M, Murakami N, Shirai M, Yoshimatsu H, Kangawa K, Kojima M (2004) Neuromedin U has a novel anorexigenic effect independent of the leptin signaling pathway. Nat Med 10:1067–1073 PubMedCrossRefGoogle Scholar
  9. Hanada T, Date Y, Shimbara T, Sakihara S, Murakami N, Hayashi Y, Kanai Y, Suda T, Kangawa K, Nakazato M (2003) Central action of neuromedin U via corticotropin-releasing hormone. Biochem Biophys Res Commun 311:954–958 PubMedCrossRefGoogle Scholar
  10. Hedrick JA, Morse K, Shan L, Qiao X, Pang L, Wang S, Laz T, Gustafson EL, Bayne M, Monsma FJ Jr (2000) Identification of a human gastrointestinal tract and immune system receptor for the peptide neuromedin U. Mol Pharmacol 58:870–875 PubMedGoogle Scholar
  11. 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 (2000) Identification and functional characterization of a novel subtype of neuromedin U receptor. J Biol Chem 275:29528–29532 PubMedCrossRefGoogle Scholar
  12. Howard AD, Wang R, Pong SS, Mellin TN, Strack A, Guan XM, Zeng Z, Williams DL Jr, 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 LHT, Liu Q (2000) Identification of receptors for neuromedin U and its role in feeding. Nature 406:70–74 PubMedCrossRefGoogle Scholar
  13. Ida T, Mori K, Miyazato M, Egi Y, Abe S, Nakahara K, Nishihara M, Kangawa K, Murakami N (2005) Neuromedin S is a novel anorexigenic hormone. Endocrinology 146:4217–4223 PubMedCrossRefGoogle Scholar
  14. Kojima M, Haruno R, Nakazato M, Date Y, Murakami N, Hanada R, Matsuo H, Kangawa K (2000) Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3). Biochem Biophys Res Commun 276:435–438 PubMedCrossRefGoogle Scholar
  15. Lowrey PL, Takahashi JS (2000) Genetics of the mammalian circadian system: photic entrainment, circadian pacemaker mechanisms, and posttranslational regulation. Annu Rev Genet 34:533–562 PubMedCrossRefGoogle Scholar
  16. Minamino N, Kangawa K, Matsuo H (1985) Neuromedin U-8 and U-25: novel uterus stimulating and hypertensive peptides identified in porcine spinal cord. Biochem Biophys Res Commun 130:1078–1085 PubMedCrossRefGoogle Scholar
  17. Mori K, Miyazato M, Ida T, Murakami N, Serino R, Ueta Y, Kojima M, Kangawa K (2005) Identification of neuromedin S and its possible role in the mammalian circadian oscillator system. EMBO J 24:325–335 PubMedCrossRefGoogle Scholar
  18. Moriyama M, Sato T, Inoue H, Fukuyama S, Teranishi H, Kangawa K, Kano T, Yoshimura A, Kojima M (2005) The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells. J Exp Med 202:217–224 PubMedCrossRefGoogle Scholar
  19. Mrosovsky N (1996) Locomotor activity and non-photic influences on circadian clocks. Biol Rev 71:343–372 PubMedCrossRefGoogle Scholar
  20. Nakahara K, Hanada R, Murakami N, Teranishi H, Ohgusu H, Fukushima N, Moriyama M, Ida T, Kangawa K, Kojima M (2004a) The gut–brain peptide neuromedin U is involved in the mammalian circadian oscillator system. Biochem Biophys Res Commun 318:156–161 PubMedCrossRefGoogle Scholar
  21. Nakahara K, Kojima M, Hanada R, Egi Y, Ida T, Miyazato M, Kangawa K, Murakami N (2004b) Neuromedin U is involved in nociceptive reflexes and adaptation to environmental stimuli in mice. Biochem Biophys Res Commun 323:615–620 PubMedCrossRefGoogle Scholar
  22. Nakazato M, Hanada R, Murakami N, Date Y, Mondal MS, Kojima M, Yoshimatsu H, Kangawa K, Matsukura S (2000) Central effects of neuromedin U in the regulation of energy homeostasis. Biochem Biophys Res Commun 277:191–194 PubMedCrossRefGoogle Scholar
  23. Piggins HD, Cutler DJ (2003) The roles of vasoactive intestinal polypeptide in the mammalian circadian clock. J Endocrinol 177:7–15 PubMedCrossRefGoogle Scholar
  24. 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 (2000) Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system. J Biol Chem 275:32452–32459 PubMedCrossRefGoogle Scholar
  25. Reppert SM, Weaver DR (2001) Molecular analysis of mammalian circadian rhythms. Ann Rev Physiol 63:647–676 CrossRefGoogle Scholar
  26. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941 PubMedCrossRefGoogle Scholar
  27. Sakamoto T, Mori K, Nakahara K, Miyazato M, Kangawa K, Samejima H, Murakami N (2007) Neuromedin S exerts an antidiuretic action in rats. Biochem Biophys Res Commun 361:457–461 PubMedCrossRefGoogle Scholar
  28. Shousha S, Nakahara K, Sato M, Mori K, Miyazato M, Kangawa K, Murakami N (2005) Effect of neuromedin S on feeding regulation in the Japanese quail. Neurosci Lett 391:87–90 PubMedCrossRefGoogle Scholar
  29. Tan CP, McKee KK, Liu Q, Palyha OC, Feighner SD, Hreniuk DL, Smith RG, Howard AD (1998) Cloning and characterization of a human and murine T-cell orphan G-protein-coupled receptor similar to the growth hormone secretagogue and neurotensin receptors. Genomics 52:223–229 PubMedCrossRefGoogle Scholar
  30. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR, Eckel RH, Takahashi JS, Bass J (2005) Obesity and metabolic syndrome in circadian clock mutant mice. Science 308:1043–1045 PubMedCrossRefGoogle Scholar
  31. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC, Bergmann JE, Gaitanaris GA (2003) The G protein-coupled receptor repertories of human and mouse. Proc Natl Acad Sci USA 100:4903–4908 PubMedCrossRefGoogle Scholar
  32. Vigo E, Roa J, López M, Castellano JM, Fernandez-Fernandez R, Navarro VM, Pineda R, Aguilar E, Diéguez C, Pinilla L, Tena-Sempere M (2007) Neuromedin S as novel putative regulator of luteinizing hormone secretion. Endocrinology 148:813–823 PubMedCrossRefGoogle Scholar
  33. Yu XH, Cao CQ, Mennicken F, Puma C, Dray A, O'Donnell D, Ahmad S, Perkins M (2003) Pro-nociceptive effects of neuromedin U in rat. Neuroscience 120:467–474 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  1. 1.Department of BiochemistryNational Cardiovascular Center Research InstituteOsaka 565-8565Japan

Personalised recommendations