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Gene Review

NMU  -  neuromedin U

Homo sapiens

Synonyms: Neuromedin-U
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Disease relevance of NMU


Psychiatry related information on NMU

  • NmU caused a marked increase in grooming and motor activity but did not affect PPI [6].
  • These results suggest that NMU plays a role in feeding behavior and catabolic functions via CRH [7].
  • The mean latency period was significantly lengthened in all the treated groups as compared to that in the only NMU-administered rats (P < 0.001) [8].

High impact information on NMU

  • Peripheral activities of NMU include stimulation of smooth muscle, increase of blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function [9].
  • Intracerebroventricular administration of NMU markedly suppresses food intake in rats [9].
  • NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting [9].
  • To determine the cytotoxicity of 7,12-dimethylbenz[a]anthracene (DMBA) and N-nitroso-N-methylurea (NMU) on primary cultures of rat mammary cells, cultures were exposed to various concentrations of these carcinogens [10].
  • Exposing Indo-1-labeled K562 cells to NmU induced an intracellular Ca(++) flux consistent with engagement of the NMU1R [3].

Chemical compound and disease context of NMU

  • The principal site of action of these agents was the forestomach, squamous cell papillomas of this organ developing in 53 and 61% of the animals receiving the higher doses of NMU and N-nitroso-N-ethylurea, respectively [11].
  • Recently, we have demonstrated the malignant transformation of HPV-18 C-1 cells after multiple exposures to the chemical carcinogen N-nitroso-N-methylurea (NMU) [12].
  • Replacing the geminal methyl groups on the calcitriol-related side chain of these gemini compounds with trideuteriomethyl moieties further boosted the potency in the colon cancer model in mice some 10-fold, reduced NMU-induced breast cancer carcinogenesis in rats and decreased the IC(50) values for renin mRNA inhibition into the pM range [13].
  • CONCLUSIONS: We propose that the local RAS in pineal gland is modified in rats with breast cancer induced by NMU through the inhibition of AspAP activity, which may lead to increased levels of Ang II [14].

Biological context of NMU


Anatomical context of NMU


Associations of NMU with chemical compounds


Physical interactions of NMU

  • NMU binds to GPR66-expressing cells with high specificity to induce intracellular calcium mobilization [20].

Regulatory relationships of NMU

  • Here we demonstrate that GPR66/FM-3 is specifically stimulated by NmU, causing the mobilization of intracellular calcium [21].
  • 2. The prototype chemical carcinogens NMU and BP induce amplified expression of ras protooncogene in benign (noninvolved) human mammary TDLU [22].
  • TAM suppressed carcinogenesis to 0% incidence like TAM+MEL in both the NMU and DMBA models [23].
  • Neuromedin U and pituitary adenylate cyclase activating peptide (PACAP) have recently been demonstrated in gut nerves [24].

Other interactions of NMU


Analytical, diagnostic and therapeutic context of NMU


  1. The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia. Moriyama, M., Fukuyama, S., Inoue, H., Matsumoto, T., Sato, T., Tanaka, K., Kinjyo, I., Kano, T., Yoshimura, A., Kojima, M. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  2. The neuromedin u-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer. Takahashi, K., Furukawa, C., Takano, A., Ishikawa, N., Kato, T., Hayama, S., Suzuki, C., Yasui, W., Inai, K., Sone, S., Ito, T., Nishimura, H., Tsuchiya, E., Nakamura, Y., Daigo, Y. Cancer Res. (2006) [Pubmed]
  3. Neuromedin U: a Myb-regulated autocrine growth factor for human myeloid leukemias. Shetzline, S.E., Rallapalli, R., Dowd, K.J., Zou, S., Nakata, Y., Swider, C.R., Kalota, A., Choi, J.K., Gewirtz, A.M. Blood (2004) [Pubmed]
  4. Screening of active compounds as neuromedin U2 receptor agonist from natural products. Zheng, X., Hu, Y., Liu, J., Ouyang, K. Bioorg. Med. Chem. Lett. (2005) [Pubmed]
  5. 1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), a new deltanoid (vitamin D analogue) for prevention of breast cancer in the rat. Anzano, M.A., Smith, J.M., Uskoković, M.R., Peer, C.W., Mullen, L.T., Letterio, J.J., Welsh, M.C., Shrader, M.W., Logsdon, D.L., Driver, C.L. Cancer Res. (1994) [Pubmed]
  6. Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats. Gartlon, J., Szekeres, P., Pullen, M., Sarau, H.M., Aiyar, N., Shabon, U., Michalovich, D., Steplewski, K., Ellis, C., Elshourbagy, N., Duxon, M., Ashmeade, T.E., Harrison, D.C., Murdock, P., Wilson, S., Ennaceur, A., Atkins, A., Heidbreder, C., Hagan, J.J., Hunter, A.J., Jones, D.N. Psychopharmacology (Berl.) (2004) [Pubmed]
  7. Central actions of neuromedin U via corticotropin-releasing hormone. Hanada, T., Date, Y., Shimbara, T., Sakihara, S., Murakami, N., Hayashi, Y., Kanai, Y., Suda, T., Kangawa, K., Nakazato, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. Combination of melatonin and tamoxifen as a chemoprophylaxis against N-nitroso-N-methylurea-induced rat mammary tumors. Kothari, A., Borges, A., Ingle, A., Kothari, L. Cancer Lett. (1997) [Pubmed]
  9. Identification of receptors for neuromedin U and its role in feeding. Howard, A.D., Wang, R., Pong, S.S., Mellin, T.N., Strack, A., Guan, X.M., Zeng, Z., Williams, D.L., Feighner, S.D., Nunes, C.N., Murphy, B., Stair, J.N., Yu, H., Jiang, Q., Clements, M.K., Tan, C.P., McKee, K.K., Hreniuk, D.L., McDonald, T.P., Lynch, K.R., Evans, J.F., Austin, C.P., Caskey, C.T., Van der Ploeg, L.H., Liu, Q. Nature (2000) [Pubmed]
  10. Primary culture of rat mammary epithelial cells. II. Cytotoxic effect and metabolism of 7,12-dimethylbenz[a]anthracene and N-nitroso-N-methylurea. Richards, J., Nandi, S. J. Natl. Cancer Inst. (1978) [Pubmed]
  11. Carcinogenicity of single doses of N-nitroso-N-methylurea and N-nitroso-N-ethylurea in Syrian golden hamsters and the persistence of alkylated purines in the DNA of various tissues. Likhachev, A.J., Ivanov, M.N., Brésil, H., Planche-Martel, G., Montesano, R., Margison, G.P. Cancer Res. (1983) [Pubmed]
  12. Molecular and genetic mechanisms of prostate cancer. Rhim, J.S. Radiat. Res. (2001) [Pubmed]
  13. Calcitriol derivatives with two different side chains at C-20 III. An epimeric pair of the gemini family with unprecedented antiproliferative effects on tumor cells and renin mRNA expression inhibition. Maehr, H., Uskokovic, M., Adorini, L., Penna, G., Mariani, R., Panina, P., Passini, N., Bono, E., Perego, S., Biffi, M., Holick, M., Spina, C., Suh, N. J. Steroid Biochem. Mol. Biol. (2007) [Pubmed]
  14. Renin-angiotensin system-regulating aminopeptidase activities are modified in the pineal gland of rats with breast cancer induced by N-methyl-nitrosourea. Carrera, M.P., Ramírez-Expósito, M.J., Valenzuela, M.T., Dueñas, B., García, M.J., Mayas, M.D., Martínez-Martos, J.M. Cancer Invest. (2006) [Pubmed]
  15. Neuromedin U stimulates contraction of human long saphenous vein and gastrointestinal smooth muscle in vitro. Jones, N.A., Morton, M.F., Prendergast, C.E., Powell, G.L., Shankley, N.P., Hollingsworth, S.J. Regul. Pept. (2006) [Pubmed]
  16. Characterization of neuromedin U effects in canine smooth muscle. Westfall, T.D., McCafferty, G.P., Pullen, M., Gruver, S., Sulpizio, A.C., Aiyar, V.N., Disa, J., Contino, L.C., Mannan, I.J., Hieble, J.P. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  17. Identification and functional characterization of a novel subtype of neuromedin U receptor. 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. J. Biol. Chem. (2000) [Pubmed]
  18. Regulation of gonadotropin secretion and puberty onset by neuromedin U. Fukue, Y., Sato, T., Teranishi, H., Hanada, R., Takahashi, T., Nakashima, Y., Kojima, M. FEBS Lett. (2006) [Pubmed]
  19. Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis. Nogueiras, R., Tovar, S., Mitchell, S.E., Barrett, P., Rayner, D.V., Dieguez, C., Williams, L.M. J. Endocrinol. (2006) [Pubmed]
  20. Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3). Kojima, M., Haruno, R., Nakazato, M., Date, Y., Murakami, N., Hanada, R., Matsuo, H., Kangawa, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  21. Identification of a human gastrointestinal tract and immune system receptor for the peptide neuromedin U. Hedrick, J.A., Morse, K., Shan, L., Qiao, X., Pang, L., Wang, S., Laz, T., Gustafson, E.L., Bayne, M., Monsma, F.J. Mol. Pharmacol. (2000) [Pubmed]
  22. Cellular ras protooncogene expression in human mammary explant cultures. A potential marker for chemical carcinogenesis. Telang, N.T., Basu, A., Modak, M.J., Osborne, M.P. Ann. N. Y. Acad. Sci. (1990) [Pubmed]
  23. Effects of tamoxifen and melatonin on mammary gland cancer induced by N-methyl-N-nitrosourea and by 7,12-dimethylbenz(a)anthracene, respectively, in female Sprague-Dawley rats. Kubatka, P., Bojková, B., M ciková-Kalická, K., Mníchová-Chamilová, M., Adámeková, E., Ahlers, I., Ahlersová, E., Cermáková, M. Folia Biol. (Praha) (2001) [Pubmed]
  24. The neuroendocrine system of the gut--an update. Sundler, F., Ekblad, E., Håkanson, R. Acta oncologica (Stockholm, Sweden) (1991) [Pubmed]
  25. Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system. Raddatz, R., Wilson, A.E., Artymyshyn, R., Bonini, J.A., Borowsky, B., Boteju, L.W., Zhou, S., Kouranova, E.V., Nagorny, R., Guevarra, M.S., Dai, M., Lerman, G.S., Vaysse, P.J., Branchek, T.A., Gerald, C., Forray, C., Adham, N. J. Biol. Chem. (2000) [Pubmed]
  26. Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3. Szekeres, P.G., Muir, A.I., Spinage, L.D., Miller, J.E., Butler, S.I., Smith, A., Rennie, G.I., Murdock, P.R., Fitzgerald, L.R., Wu, H., McMillan, L.J., Guerrera, S., Vawter, L., Elshourbagy, N.A., Mooney, J.L., Bergsma, D.J., Wilson, S., Chambers, J.K. J. Biol. Chem. (2000) [Pubmed]
  27. Cloning and characterization of the cDNA encoding the human neuromedin U (NmU) precursor: NmU expression in the human gastrointestinal tract. Austin, C., Lo, G., Nandha, K.A., Meleagros, L., Bloom, S.R. J. Mol. Endocrinol. (1995) [Pubmed]
  28. Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia. Wu, Y., McRoberts, K., Berr, S.S., Frierson, H.F., Conaway, M., Theodorescu, D. Oncogene (2007) [Pubmed]
  29. Molecular cloning of rat Krev-1 cDNA and analysis of the mRNA levels in normal and NMU-induced mammary carcinomas. Hong, H.J., Hsu, L.C., Gould, M.N. Carcinogenesis (1990) [Pubmed]
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