Skip to main content

Advertisement

SpringerLink
Log in

Neuromedin: An insight into its types, receptors and therapeutic opportunities

  • Review article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Neuropeptides are small protein used by neurons in signal communications. Neuromedin U was the first neuropeptide discovered from the porcine spinal and showed its potent constricting activities on uterus hence was entitled with neuromedin U. Following neuromedin U another of its isoform was discovered neuromedin S which was observed in suprachiasmatic nucleus hence was entitled neuromedin S. Neuromedin K and neuromedin L are of kanassin class which belong to tachykinin family. Bombesin family consists of neuromedin B and neuromedin C. All these different neuromedins have various physiological roles like constrictive effects on the smooth muscles, control of blood pressure, pain sensations, hunger, bone metastasis and release and regulation of hormones. Over the years various newer physiological roles have been observed thus opening ways for various novel therapeutic treatments. This review aims to provide an overview of important different types of neuromedin, their receptors, signal transduction mechanism and implications for various diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ACTH:

Adrenocorticotrophic hormone

CRH:

Corticotrophin releasing hormone

FSH:

Follicle stimulating hormone

GIT:

Gastrointestinal tract

GPCRs:

G-Protein Coupled Receptors

GRP:

Gastrin releasing peptide

LH:

Luteinizing hormone

NMB:

Neuromedin B

NMC:

Neuromedin C

NMK:

Neuromedin K

NML:

Neuromedin L

NMS:

Neuromedin S

NMU:

Neuromedin U

NMULIR:

NMU like immunoreactivity

PVN:

Paraventricular nucleus

RIA:

Radioimmunoassay

RT-PCR:

Reverse Transcriptase- Polymer Chain Reaction

SCN:

Suprachiasmatic nucleus

TRH:

Thyroid releasing hormone

References

  1. Civelli O. Functional genomics: the search for novel neurotransmitters and neuropeptides. FEBS Lett 1998;430:55–8.

    Article  CAS  PubMed  Google Scholar 

  2. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. The G protein coupled receptor repertories of human and mouse. Proc Natl Acad Sci U S A 2003;100:4903–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Civelli O, Saito Y, Wang Z, Nothacker HP, Reinscheid RK. Orphan GPCRS and their ligands. Pharmacol Ther 2006;110:522–5.

    Article  CAS  Google Scholar 

  4. Kangawa K, Minamino N, Fukuda A, Matsuo H. Neuromedin-K — a novel mammalian tachykinin identified in porcine spinal-cord. Biochem Biophys Res Commun 1983;114:533–40.

    Article  CAS  PubMed  Google Scholar 

  5. Minamino N, Kangawa K, Fukuda A, Matsuo H. Neuromedin-L — a novel mammalian tachykinin identified in porcine spinal-cord. Neuropeptides 1984;4:157–66.

    Article  CAS  PubMed  Google Scholar 

  6. Minamino N, Kangawa K, Matsuo H. Neuromedin-C — a bombesin-like peptide identified in porcine spinal-cord. Biochem Biophys Res Commun 1984;119:14–20.

    Article  CAS  PubMed  Google Scholar 

  7. Minamino N, Kangawa K, Matsuo H. Neuromedin-N — a novel neurotensin-like peptide identified in porcine spinal-cord. Biochem Biophys Res Commun 1984;122:542–9.

    Article  CAS  PubMed  Google Scholar 

  8. Minamino N, Kangawa K, Matsuo H. Neuromedin-U-8 and neuromedin-U-25 — novel uterus stimulating and hypertensive peptides identified in porcine spinal-cord. Biochem Biophys Res Commun 1985;130:1078–85.

    Article  CAS  PubMed  Google Scholar 

  9. Minamino N, Sudoh T, Kangawa K, Matsuo H. Neuromedins—novel Smooth-muscle stimulating peptides identified in porcine spinal-cord. Peptides 1985;6:245–8.

    Article  CAS  PubMed  Google Scholar 

  10. Brighton PJ, Szekeres PG, Willars GB. Neuromedin U and its receptors: structure, function, and physiological roles. Pharmacol Rev 2004;56(2):231–48.

    Article  CAS  PubMed  Google Scholar 

  11. Brighton PJ, Wise A, Dass NB, Willars GB. Paradoxical behaviour of neuromedin U in isolated smooth muscle cells and intact tissue. J Pharmacol Exp Ther 2008;325(1):154–64.

    Article  CAS  PubMed  Google Scholar 

  12. Torres R, Croll SD, Vercollone J, Reinhardt J, Griffiths J, Zabski S, et al. Mice genetically deficient in neuromedin U receptor 2, but not neuromedin U receptor 1, have impaired nociceptive response. Pain 2007;130(3):267–78.

    Article  CAS  PubMed  Google Scholar 

  13. Novak CM, Zhang M, Levine JA. Sensitivity of the hypothalamic paraventricular nucleus to the loco motor-activating effects of neuromedin U in obesity. Brain Res 2007;1169:57–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Vigo E, Roa J, Pineda R, Castellano JM, Navarro VM, Aguilar E, et al. Novel role of the anorexigenic peptide neuromedin U in the control of LH secretion and its regulation by gonadal hormones and photoperiod. Am J Physiol Endocrinol Metab 2007;293(5):E1265–73.

    Article  CAS  PubMed  Google Scholar 

  15. Iwai T, Iinuma Y, Kodani R, Oka J. Neuromedin U inhibits inflammation-mediated memory impairment and neuronal cell-death in rodents. Neurosci Res 2008;61(1):113–9.

    Article  CAS  PubMed  Google Scholar 

  16. Tanida M, Satomi J, Shen J, Nagai K. Autonomic and cardiovascular effects of central neuromedin U in rats. Physiol Behav 2009;96(2):282–8.

    Article  CAS  PubMed  Google Scholar 

  17. Mitchell JD, Maguire JJ, Kuc RE, Davenport AP. Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system. Cardiovasc Res 2009;81(2):353–61.

    Article  CAS  PubMed  Google Scholar 

  18. Lee WH, Liu SB, Shen JH, Jin Y, Lai R, Zhang Y. Identification and molecular cloning of a novel neuromedin U analogue from the skin secretions of toad Bombina maxima. Regul Pept 2005;129:43–7.

    Article  CAS  PubMed  Google Scholar 

  19. Austin C, Lo G, Nandha KA, Meleagros L, Bloom SR. Cloning and characterization of the cDNA encoding the human neuromedin U (NmU) precursor: NmU expression in the human gastrointestinal tract. J Mol Endocrinol 1995;14:157–69.

    Article  CAS  PubMed  Google Scholar 

  20. Domin J, Ghatei MA, Chohan P, Bloom SR. NmU — a study of its distribution in the rat. Peptides 1987;8:779–84.

    Article  CAS  PubMed  Google Scholar 

  21. Shan L, Qiao X, Crona JH, et al. Identification of a novel neuromedin U receptor subtype expressed in the central nervous system. J Biol Chem 2000;275:39482–6.

    Article  CAS  PubMed  Google Scholar 

  22. Raddatz R, Wilson AE, Artymyshyn R. Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system. J Biol Chem 2000;275:32452–9.

    Article  CAS  PubMed  Google Scholar 

  23. Guan XM, Yu H, Jiang Q, Van Der Ploeg LH, Liu Q. Distribution of neuromedin U receptor subtype 2 mRNA in the rat brain. Brain Res Gene Expr Patterns 2001;1:1–4.

    Article  CAS  PubMed  Google Scholar 

  24. Austin C, Oka M, Nandha KA, Legon S, Khandannia N, Lo G, et al. Distribution and developmental pattern of neuromedin-U expression in the rat gastrointestinal-tract. J Mol Endocrinol 1994;12:257–63.

    Article  CAS  PubMed  Google Scholar 

  25. Augood SJ, Keast JR, Emson PC. Distribution and characterization of neuromedin-U-like immunoreactivity in rat-brain and intestine and in guinea-pig intestine. Regul Pept 1988;20:281–92.

    Article  CAS  PubMed  Google Scholar 

  26. Ballesta J, Carlei F, Bishop AE, Steel JH, Gibson SJ, Fahey M, et al. Occurrence and developmental pattern of neuromedin U-immunoreactivity nerves in the gastrointestinal-tract and brain of the rat. Neuroscience 1988;25:797–816.

    Article  CAS  PubMed  Google Scholar 

  27. Bishop AE, Ballesta J, Carlei F, Steel JH, Gibson SJ, Fahey M, et al. The distribution and development of a new brain and gut peptide, neuromedin-U. J Pathol 1988;154:A99–A100.

    Google Scholar 

  28. Honzawa M, Sudoh T, Minamino N, Kangawa K, Matsuo H. Neuromedin U-like immunoreactivity in rat intestine — regional distribution and immune histochemical study. Neuropeptides 1990;15:1–9.

    Article  CAS  PubMed  Google Scholar 

  29. Hedrick JA, Morse K, Shan L. Identification of a human gastrointestinal tract and immune system receptor for the peptide neuromedin U. Mol Pharmacol 2000;58:870–5.

    Article  CAS  PubMed  Google Scholar 

  30. Chen TB, Zhou M, Walker B, Harriot P, Mori K, Miyazato M. Structural and functional analogs of the novel mammalian neuropeptide, neuromedin S (NmS), in the dermal venoms of Eurasian bombinid toads. Biochem Biophys Res Commun 2006;345:377–84.

    Article  CAS  PubMed  Google Scholar 

  31. Mori K, Miyazato M, Ida T, Murakami N, Serino R, Ueta Y. Identification of neuromedin S and its possible role in the mammalian circadian oscillator system. EMBO J 2005;24:325–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Reppert SM, Weaver DR. Molecular analysis of mammalian circadian rhythms. Ann Rev Physiol 2001;63:647–76.

    Article  CAS  Google Scholar 

  33. Tan CP, McKee KK, Liu Q, Palyha OC, Feighner SD, Hreniuk DL, et al. 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 1998;52:223–9.

    Article  CAS  PubMed  Google Scholar 

  34. Fujii R, Hosoya M. Fukusumi Identification of neuromedin U as the cognate ligands of the orphans G protein coupled receptor FM3. Biochem Biophys Res Commun 2000;275:21068–74.

    Article  CAS  Google Scholar 

  35. Hosoya M, Moriya T, Kawamata Y, Ohkubo S, Fujii R, Matsui H, et al. Identification and functional characterization of a novel subtype of neuromedin U receptor. Biochem Biophys Res Commun 2000;275:29528–32.

    CAS  Google Scholar 

  36. Anastasi A, Erspamer V, Bucci M. Isolation and structure of bombesin and alytesin, 2 analogues active peptides from the skin of the European amphibians Bombina and Alytes. Experientia 1971;27:166–7.

    Article  CAS  PubMed  Google Scholar 

  37. Tacht Y, Brown M. On the role of bombesin in homeostasis. Trends Neurosci 1982;5:431–3.

    Article  Google Scholar 

  38. Spindel E. Mammalian bombesin-like peptides. Trends Neurosci 1986;9:130–3.

    Article  CAS  Google Scholar 

  39. McDonald TJ, Jornvall H, Nilsson G, Vagne M, Ghatei M, Bloom SR, et al. Characterization of a gastrin releasing peptide from porcine non-antral gastric tissue. Biochem Biophys Res Commun 1979;90:227–33.

    Article  CAS  PubMed  Google Scholar 

  40. Erspamer V, Erpamer GF, Inselvini M. Some pharmacological actions of alytesin and bombesin. J Pharm Pharmacol 1970;22:875–6.

    Article  CAS  PubMed  Google Scholar 

  41. Ohki-Hamazaki H, Iwabuchi M, Maekawa F. Development and function of bombesin-like peptides and their receptors. Int J Dev Biol 2005;49:293–300.

    Article  CAS  PubMed  Google Scholar 

  42. Minamino N, Kangawa K, Matsuo H. Neuromedin B and neuromedin Ca two mammalian bombesin-like peptides identified in porcine spinal cord and brain. Ann N Y Acad Sci 1988;547:373–90.

    Article  CAS  PubMed  Google Scholar 

  43. Merali Z, McIntosh J, Anisman H. Role of bombesin-related peptides in the control of food intake. Neuropeptides 1999;33:376–86.

    Article  CAS  PubMed  Google Scholar 

  44. Ghatei MA, Jung RT, Stevenson JC, Hillyard CJ, Adrian TE, Lee YC, et al. Bombesin: action on gut hormones and calcium in man. J Clin Endocrinol Metab 1982;54:980–5.

    Article  CAS  PubMed  Google Scholar 

  45. Bertaccini G, Erspamer V, Melchiorri P, Sopranzi N. Gastrin release by bombesin in the dog. Br J Pharmacol 1974;52:219–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Delle Fave G, Kohn A, de Magistris L, Mancuso M, Sparvoli C. Effect of Bombesin stimulated gastrin on gastric acid secretion in man. Life Sci 1980;27:993–9.

    Article  CAS  PubMed  Google Scholar 

  47. Walsh JH, Wong HC, Dockray GJ. Bombesin-like peptides in mammals. Fed Proc 1979;38:2315–9.

    CAS  PubMed  Google Scholar 

  48. Kirkham TC, Perez S, Gibbs J. Prefeeding potentiates anorectic actions of neuromedin B and gastrin releasing peptide. Physiol Behav 1995;58:1175–9.

    Article  CAS  PubMed  Google Scholar 

  49. Ladenheim EE, Taylor JE, Coy DH, Moore KA, Moran TH. Hindbrain GRP receptor blockade antagonizes feeding suppression by peripherally administered GRP. Am J Physiol 1996;271:R180–4.

    CAS  PubMed  Google Scholar 

  50. Kawai K, Mukai H, Yuzawa K, Suzuki S, Kuzuya N, Fujii K, et al. Effects of neuromedinB and GRP-10 on gastrin and insulin release from cultured tumor cells of a malignant gastrinoma. Endocrinol Jpn 1990;37:857–65.

    Article  CAS  PubMed  Google Scholar 

  51. Moody TW, Carney DN, Cuttitta F, Quattrocchi K, Minna JD. High affinity receptors for bombesin/GRP-like peptides on human small cell lung cancer. Life Sci 1985;37:105–13.

    Article  CAS  PubMed  Google Scholar 

  52. Moody TW, Merali Z. Bombesin-like peptides and associated receptors within the brain: distribution and behavioral implications. Peptides 2004;25:511–20.

    Article  CAS  PubMed  Google Scholar 

  53. Bedard T, Mountney C, Kent P, Anisman H, Merali Z. Role of gastrin-releasing peptide and neuromedin B in anxiety and fear-related behavior. Behav Brain Res 2007;179:133–40.

    Article  CAS  PubMed  Google Scholar 

  54. Roesler R, Henriques JA, Schwartsmann G. Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurological disorders. CNS Neurol Disord Drug Targets 2006;5:197–204.

    Article  CAS  PubMed  Google Scholar 

  55. Linari G, Linari MB. Effect of bombesin on pancreatic secretion and gall bladder motility of the chicken. Eur J Pharmacol 1975;34:305–10.

    Article  CAS  PubMed  Google Scholar 

  56. Mayer EA, Elashoff J, Walsh JH. Characterization of bombesin effects on canine gastric muscle. Am J Physiol 1982;243:G141–7.

    CAS  PubMed  Google Scholar 

  57. Zafirov DH, Palmer JM, Nemeth PR, Wood JD. Bombesin, gastrin releasing peptide and vasoactive intestinal peptide excite myenteric neurons. Eur J Pharmacol 1985;115:103–7.

    Article  CAS  PubMed  Google Scholar 

  58. Washington MC, Sayegh AI. Gastrin releasing peptides increase Fos-like immunoreactivity in the enteric nervous system and the dorsal vagal complex. Peptides 2012;32:1600–5.

    Article  CAS  Google Scholar 

  59. McDonald TJ, Ghatei MA, Bloom SR, Adrian TE, Mochizuki T, Yanaihara C, et al. Dose-response comparisons of canine plasma gastroenteropancreatic hormone responses to bombesin and the porcine gastrin-releasing peptide (GRP). Regul Pept 1983;5:125–37.

    Article  CAS  PubMed  Google Scholar 

  60. Ruff M, Schiffmann E, Terranova V, Pert CB. Neuropeptides are chemoattractants for human tumor cells and monocytes: a possible mechanism for metastasis. Clin Immunol Immunopathol 1985;37:387–96.

    Article  CAS  PubMed  Google Scholar 

  61. De la Fuente M, Del Rio M, Ferrandez MD, Hernanz A. Modulation of phagocytic function in murine peritoneal macrophages by bombesin, gastrin-releasing peptide and neuromedin C. Immunology 1991;73:205–11.

    PubMed  PubMed Central  Google Scholar 

  62. van Tol EA, Verspaget HW, Hansen BE, Lamers CB. Neuroenteric peptides affect natural killer activity by intestinal lamina propria mononuclear cells. J Neuroimmunol 1993;42:139–45.

    Article  PubMed  Google Scholar 

  63. Del Rio M, Hernanz A, de la Fuente M. Bombesin gastrin-releasing peptide, and neuromedinC modulate murine lymphocyte proliferation through adherent accessory cells and activate protein kinase C. Peptides 1994;5:15–22.

    Google Scholar 

  64. Narayan S, Guo YS, Townsend Jr. CM, Singh P. Specific binding and growth effects of bombesin-related peptides on mouse colon cancer cells in vitro. Cancer Res 1990;50:6772–8.

    CAS  PubMed  Google Scholar 

  65. Viallet J, Minna JD. Gastrin-releasing peptide (GRP, mammalian bombesin) in the pathogenesis of lung cancer. Prog Growth Factor Res 1989;1:89–97.

    Article  CAS  PubMed  Google Scholar 

  66. Bologna M, Festuccia C, Muzi P, Biordi L, Ciomei M. Bombesin stimulates growth of human prostatic cancer cells in vitro. Cancer 1989;63:1714–20.

    Article  CAS  PubMed  Google Scholar 

  67. Walsh JH, Wong HC, Dockray GJ. Bombesin Like peptides in mammals. Fed Proc 1979;2:2315–9.

    Google Scholar 

  68. Moody TW, Thoa NE, O’Donohue L, Jacobowitz DM. Reduced Gastrin releasing peptide in CSF after recovery from bulimia. Life Sci 1981;2:2273–9.

    Article  Google Scholar 

  69. Kimura S, Goto K, Ogawa T, Sugita Y, Kanazawa I, Munekata E. Novel neuropeptides, Neurokinin α and β, isolated from porcine spinal cord. Proc Jpn Acad 1983;59:101–4.

    Article  CAS  Google Scholar 

  70. Dobner PR, Barber DL, Villa-Komaroff L, McKiernan C. Cloning and sequence analysis of cDNA for the canine neuro- tensin/neuromedin N precursor. Proc Natl Acad Sci U S A 1987;54:3516–20.

    Article  Google Scholar 

  71. Checler F, Vincent JR, Kitabgi R. Neuromedin N: high- affinity interaction with brain neurotensin receptors and rapid inactivation by brain synaptic peptidases. Eur J Pharmacol 1986;126:239–44.

    Article  CAS  PubMed  Google Scholar 

  72. Tanaka K, Masu M, Nakanishi S. Structure and functional expression of the cloned rat neurotensin receptor. Neuron 1990;4:847–54.

    Article  CAS  PubMed  Google Scholar 

  73. Erspamer VGBJ Glass. Gastrointestinal Hormones. New York: Raven Press; 1980. p. 343–61.

    Google Scholar 

  74. Harmar AJ. Three tachykinins in mammalian brain. Trends Neurosci 1984;7:57.

    Article  CAS  PubMed Central  Google Scholar 

  75. Ding YQ, Shigemoto R, Takada M, Ohishi H, Nakanishi S, Mizuno N. Localization of the neuromedin K receptor (NK3) in the central nervous system of the rat. J Comp Neurol 1996;364:290–310.

    Article  CAS  PubMed  Google Scholar 

  76. Minamino N, Kangawa K, Matsuo H. Neuromedin N: a novel neurotensin-like peptide identified in porcine spinal cord. Biochem Biophys Res Commun 1984;122:542–9.

    Article  CAS  PubMed  Google Scholar 

  77. Benito-Orfila MA, Domin J, Nandha KA, Bloom SR. The motor effect of Neuromedin-U on rat stomach in vitro. Eur J Pharmacol 1991;193:329–33.

    Article  CAS  PubMed  Google Scholar 

  78. Maggi CA, Patacchini R, Giuliani S, Turini D, Barbanti G, Rovero P, et al. Motor response of the human isolated small-intestine and urinary-bladder to porcine neuromedin U-8. Br J Pharmacol 1990;99:186–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Jones NA, Morton MF, Prendergast CE, Powell GL, Shankley NP, Hollingsworth SJ. Neuromedin U stimulates contraction of human long saphenous vein and gastrointestinal smooth muscle in vitro. Regul Pept 2006;136:109–16.

    Article  CAS  PubMed  Google Scholar 

  80. Dass NB, Bassil AK, North-Laidler VJ, Morrow R, Aziz E, Tuladhar BR. Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU receptor activation. Br J Pharmacol 2007;150:502–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Gerfen CR. Substance P (neurokinin-1) receptor mRNA is selectively expressed in cholinergic neurons and basal forebrain. Brain Res 1991;556:165–70.

    Article  CAS  PubMed  Google Scholar 

  82. Del Rio M, De La Fuente M. Chemoattractant capacity of bom- besin, gastrin-releasing peptide and neuromedin C is mediated through PKC activation in murine peritoneal leukocytes. Regul Pept 1994;49:185–93.

    Article  PubMed  Google Scholar 

  83. Brown DR, Quito FL. Neuromedin-U octapeptide alters ion-transport in porcine jejunum. Eur J Pharmacol 1988;155:159–62.

    Article  CAS  PubMed  Google Scholar 

  84. Katz R. Grooming elicited by intracerebroventricular bombesin and eledoisin in the mouse. Neuropharmacology 1980;19:143–6.

    Article  CAS  PubMed  Google Scholar 

  85. Gmerek DE, Cowan A. Studies on bombesin-induced grooming in rats. Peptides 1983;4:907–13.

    Article  CAS  PubMed  Google Scholar 

  86. Lemaire I. Bombesin-related peptides modulate interleukin-1 production by alveolar macrophages. Neuropeptides 1991;20:217–23.

    Article  CAS  PubMed  Google Scholar 

  87. Ozaki Y, Onaka T, Nakazato M, Saito J, Kanemoto K, Matsumoto T, et al. Centrally administered neuromedin U activates neurosecretion and induction of C-Fos messenger ribonucleic acid in the paraventricular and supraoptic nuclei of rat. Endocrinology 2002;143:4320–9.

    Article  CAS  PubMed  Google Scholar 

  88. Fukue Y, Sato T, Teranishi H. Regulation of gonadotropin secretion and puberty onset by neuromedin U. FEBS Lett 2006;580:3485–8.

    Article  CAS  PubMed  Google Scholar 

  89. Rokkaku K, Onaka T, Okada N. Neuromedin U facilitates oxytocin release from the pituitary via beta adrenoceptors. Neuroreport 2003;14:1997–2000.

    Article  CAS  PubMed  Google Scholar 

  90. Sakamoto T, Mori K, Miyazato M, Kangawa K, Sameshima H, Nakahara K. Involvement of neuromedin S in the oxytocin release response to suckling stimulus. Biochem Biophys Res Commun 2008;375:49–53.

    Article  CAS  PubMed  Google Scholar 

  91. Kaczmarek P, Malendowicz LK, Pruszynska-Oszmalek E. Neuromedin U receptor 1 expression in the rat endocrine pancreas and evidence suggesting neuromedin U suppressive effect on insulin secretion from isolated rat pancreatic islets. Int J Mol Med 2006;18:951–5.

    CAS  PubMed  Google Scholar 

  92. Brown M, Rivier J, Vale W. Bombesin: potent effects on thermoregulation in the rat. Science 1977;196:998–1000.

    Article  CAS  PubMed  Google Scholar 

  93. Brown M, Rivier J, Vale W. Bombesin affects the central nervous system to produce hyperglycemia in rats. Life Sci 1977;2(1):1729–34.

    Article  Google Scholar 

  94. Jin GF, Guo YS, Smith ER, Houston CW. The effect of Bombesin-related peptides on the phagocytic function of mouse phagocytes in vitro. Peptides 1990;I(I):393–6.

    Article  Google Scholar 

  95. Nakahara K, Hanada R, Murakami N. The gut brain peptide neuromedin U is involved in the mammalian circadian oscillator system. Biochem Biophys Res Commun 2004;318:56–61.

    Article  CAS  Google Scholar 

  96. Malendowicz KA, Nussdorfer GG, Nowak KW, Mazzocchi G. Effects of neuromedin U-8 on the rat pituitary-adrenocortical axis. In Vivo 1993;7:419–22.

    CAS  PubMed  Google Scholar 

  97. Hanada R, Nakazato M, Murakami N, Sakihara S, Yoshimatsu H, Toshinai K, et al. A role for Neuromedin U in stress response. Biochem Biophys Res Commun 2001;289:225–8.

    Article  CAS  PubMed  Google Scholar 

  98. Ortiga-Carvalho TM, Oliveira KJ, Soares BA, Pazos-Moura CC. The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies. J Endocrinol 2002;174:121–5.

    Article  CAS  PubMed  Google Scholar 

  99. Oliveira KJ, Ortiga-Carvalho TM, Cabanelas A, Veiga MA, Aoki K, Ohki-Hamazaki H, et al. Disruption of neuromedin B receptor gene results in dysregulation of the pituitary? thyroid axis. J Mol Endocrinol 2006;36:73–80.

    Article  CAS  PubMed  Google Scholar 

  100. Kojima M, Haruno R, Nakazato M, Date Y, Murakami N, Hanada R, et al. Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3). Biochem Biophys Res Commun 2000;276:435–8.

    Article  CAS  PubMed  Google Scholar 

  101. Nakazato M, Hanada R, Murakami N, Date Y, Mondal MS, Kojima M, et al. Central effects of neuromedin U in the regulation of energy homeostasis. Biochem Biophys Res Commun 2000;277:191–4.

    Article  CAS  PubMed  Google Scholar 

  102. Niimi M, Murao K, Taminato T. Central administration of neuromedin U activates neurons in ventrobasal hypothalamus and brainstem. Endocrine 2001;16:201–6.

    Article  CAS  PubMed  Google Scholar 

  103. Ivanov TR, Lawrence CB, Stanley PJ, Luckman SM. Evaluation of neuromedin U actions in energy homeostasis and pituitary function. Endocrinology 2002;143:3813–21.

    Article  CAS  PubMed  Google Scholar 

  104. Hanada T, Date Y, Shimbara T, Sakihara S, Murakami N, Hayashi Y, et al. Central actions of neuromedin U via corticotrophin-releasing hormone. Biochem Biophys Res Commun 2003;311:954–8.

    Article  CAS  PubMed  Google Scholar 

  105. Considine RV, Caro JF. Leptin and the regulation of body weight. Int J Biochem Cell Biol 1997;29:1255–72.

    Article  CAS  PubMed  Google Scholar 

  106. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature (Lond) 1998;395:763–70.

    Article  CAS  Google Scholar 

  107. Wren AM, Small CJ, Abbott CR, Jethwa PH, Kennedy AR, Murphy KG, et al. Hypothalamic actions of neuromedin U. Endocrinology 2002;143:4227–34.

    Article  CAS  PubMed  Google Scholar 

  108. Graham ES, Turnbull Y, Fotheringham P. Neuromedin U and Neuromedin U receptor-2 expression in the mouse and rat hypothalamus: effects of nutritional status. J Neurochem 2003;87:1165–73.

    Article  CAS  PubMed  Google Scholar 

  109. Duggan JP, Booth DA. Obesity, overeating and rapid gastric emptying in rats with ventromedial hypothalamic lesions. Science (Wash. D.C.) 1980;231:609–11.

    Article  Google Scholar 

  110. Yang YS, Song HD, Li RY, Zhou LB, Zhu ZD, Hu RM, et al. The gene expression profiling of human visceral adipose tissue and its secretory functions. Biochem Biophys Res Commun 2003;300:839–46.

    Article  CAS  PubMed  Google Scholar 

  111. Bouchard L, Drapeau V, Provencher V, Lemieux S, Chagnon Y, Rice T, et al. Neuromedin b: a strong candidate gene linking eating behaviors and susceptibility to obesity. Am J Clin Nutr 2004;80:1478–86.

    Article  CAS  PubMed  Google Scholar 

  112. Ladenheim EE, Knipp S. Capsaicin treatment differentially affects feeding suppression by bombesin-like peptides. Physiol Behav 2007;91:36–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004;92:347–55.

    Article  CAS  PubMed  Google Scholar 

  114. Zachary I, Rozengurt E. High-affinity receptors for peptides of the bombesin family in Swiss 3T3 cells. Proc Natl Acad Sci U S A 1985;82:7616–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Wunder BA, Hawkins MF, Avery DD, Swan H. The effects of bombesin injected into the anterior and posterior hypothalamus on body temperature and oxygen consumption. Neuropharmacology 1980;19:1095–7.

    Article  CAS  PubMed  Google Scholar 

  116. Babcock AM, Baker DA, Moody TW. Bombesin-induced hypothermia: a dose? response and receptor antagonist study. Pharmacol Biochem Behav 1992;43:957–60.

    Article  CAS  PubMed  Google Scholar 

  117. Itoh S, Takashima A, Itoh T, Morimoto T. Effects of neuromedins and related peptides on the body temperature of rats. Jpn J Physiol 1995;45:37–45.

    Article  CAS  PubMed  Google Scholar 

  118. Tsushima H, Mori M, Fujiwara N, Moriyama A. Pharmacological characteristics of bombesin receptor mediating hypothermia in the central nervous system of rats. Brain Res 2003;969:88–94.

    Article  CAS  PubMed  Google Scholar 

  119. Even PC, de Saint Hilaire Z, Nicolaidis S. Peripheral administration of bombesin increases metabolism in the rat. Physiol Behav 1991;49:439–42.

    Article  CAS  PubMed  Google Scholar 

  120. Porreca F, Burks T. Centrally administered bombesin affects gastric emptying and small and large bowel transit in the rat. Gastroenterology 1983;853:313–7.

    Article  Google Scholar 

  121. Tacht Y, Vale W, Rivier J, Brown M. Brain regulation of gastric secretion: influences of neuropeptides. Proc Natl Acad Sci U S A 1980;77:5515–9.

    Article  Google Scholar 

  122. Yu XH, Cao CQ, Mennicken F, Puma C, Dray A, O’Donnell D, et al. Pro-nociceptive effects of neuromedin U in rat. Neuroscience 2003;120:467–74.

    Article  CAS  PubMed  Google Scholar 

  123. Cao CQ, Yu XH, Dray A, Filosa A, Perkins MN. A pro-nociceptive role of neuromedin U in adult mice. Pain 2003;104:609–16.

    Article  CAS  PubMed  Google Scholar 

  124. Zhang X, Xu ZQ, Bao L, Dagerlind A, Hok Felt T. Complementary Distribution of Receptors for neurotensin and NPY in small neurons in Rat lumbar DRGs and regulation of the receptors and peptides after peripheral axotomy. J Neurosci 1995;15:2733–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Kalivas PW, Richardson-Carlson R, Duffy P. Neuromedin N mimics the actions of neurotensin in the ventral tegmental area but not in the nucleus accumbens. J Pharmacol Exp Ther 1986;238:1126–31.

    CAS  PubMed  Google Scholar 

  126. Bissette G, Manberg P, Nemeroff CB, Prange A. Neurotensin a biologically active peptide. Life Sci 1978;23:2173–82.

    Article  CAS  PubMed  Google Scholar 

  127. Gardiner SM, Compton AM, Bennett T, Domin J, Bloom SR. Regional hemodynamic effects of neuromedin-U in conscious rats. Am J Physiol 1990;258:R32–8.

    CAS  PubMed  Google Scholar 

  128. Dahlof B. Left ventricular hypertrophy and angiotensin II antagonists. Am J Hypertens 2001;14:174–82.

    Article  CAS  PubMed  Google Scholar 

  129. Chu C, Jin Q, Kunitake T. Cardiovascular actions of central neuromedin U in conscious rats. Regul Pept 2002;105:29–34.

    Article  CAS  PubMed  Google Scholar 

  130. Tsubota Y, Kakimoto N, Owada-Makabe K. Hypotensive effects of neuromedin U microinjected into the cardiovascular related region of the rat nucleus tractus solitarius. Neuroreport 2003;14:2387–90.

    Article  CAS  PubMed  Google Scholar 

  131. Khawaja AM, Rogers DF. Tachykinin: receptor to effector. Int J Biochem Cell Biol 1996;28:721–38.

    Article  CAS  PubMed  Google Scholar 

  132. Dubuc I, Nouel D, Coquerel A, Menard JF, Kitabgi P, Costentin J. Hypothermic effect of neuromedin N in mice and its potentiation by peptidase inhibitors. Eur J Pharmacol 1988;151:117–21.

    Article  CAS  PubMed  Google Scholar 

  133. Yamashita K, Upadhyay S, Osada M, Hoque MO, Xiao Y, Mori M, et al. Pharmacologic unmasking of epigenetically silenced tumour suppressor genes in oesophageal squamous cell carcinoma. Cancer Cell 2002;2:485–95.

    Article  CAS  PubMed  Google Scholar 

  134. Alevizos I, Mahadevappa M, Zhang X. Oral cancer in vivo gene expression profiling assisted by laser capture micro dissection and microarray analysis. Oncogene 2001;20:6196–204.

    Article  CAS  PubMed  Google Scholar 

  135. Johnson EN, Appelbaum ER, Carptenter DC. Neuromedin U elicits cytokine release in murine Th2 type T cell clone D10. G4.1. J Immunology 2004;173:7230–8.

    Article  CAS  Google Scholar 

  136. Sato S, Hanada R, Kimura A. Central control of bone remodeling by neuromedin U. Nat Med 2007;13:1234–40.

    Article  CAS  PubMed  Google Scholar 

  137. Rucinski M, Ziolkowska A, Tyczewska M, Szyszka M, Malendowicz LK. Neuromedin U directly stimulates growth of cultured rat calvarial osteoblast-like cells acting via the NMU receptor 2 isoform. Int J Mol Med 2008;22:363–8.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmacy, Nirma University, Ahmedabad, India

    Saumitra Gajjar & Bhoomika M. Patel

Authors
  1. Saumitra Gajjar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bhoomika M. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bhoomika M. Patel.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gajjar, S., Patel, B.M. Neuromedin: An insight into its types, receptors and therapeutic opportunities. Pharmacol. Rep 69, 438–447 (2017). https://doi.org/10.1016/j.pharep.2017.01.009

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2017.01.009

Keywords

Search

Navigation