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Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 415 | 5q33.1 | NMUR2 | neuromedin U receptor 2 | 4,19,44,49 |
| Mouse | 7 | 395 | 11 B1.3 | Nmur2 | neuromedin U receptor 2 | 10 |
| Rat | 7 | 395 | 10q22 | Nmur2 | neuromedin U receptor 2 | 19 |
| Gene and Protein Information Comments | ||||||
| For human NMU2, sequences encoding both 412 and 415 amino acids have been reported as a consequence of the presence of two potential translation initiation sites. It is unclear which form is expressed physiologically, although there is circumstantial evidence to favour the shorter form [4]. There is evidence for the existence of receptor haplotypes [3]. |
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| Previous and Unofficial Names |
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| FM-4 [19] | FM4 [56] | SNORF72 [44] | NMU-R2 [49] | TGR-1 [18] | |
| Database Links |
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| Specialist databases | |
| GPCRdb | nmur2_human (Hs) |
| Other databases | |
| Alphafold | Q9GZQ4 (Hs), Q8BZ39 (Mm), Q9ESQ4 (Rn) |
| ChEMBL Target | CHEMBL1075144 (Hs), CHEMBL3351217 (Mm) |
| Ensembl Gene | ENSG00000132911 (Hs), ENSMUSG00000037393 (Mm), ENSRNOG00000014081 (Rn) |
| Entrez Gene | 56923 (Hs), 216749 (Mm), 64042 (Rn) |
| Human Protein Atlas | ENSG00000132911 (Hs) |
| KEGG Gene | hsa:56923 (Hs), mmu:216749 (Mm), rno:64042 (Rn) |
| OMIM | 605108 (Hs) |
| Pharos | Q9GZQ4 (Hs) |
| RefSeq Nucleotide | NM_020167 (Hs), NM_153079 (Mm), NM_022275 (Rn) |
| RefSeq Protein | NP_064552 (Hs), NP_694719 (Mm), NP_071611 (Rn) |
| UniProtKB | Q9GZQ4 (Hs), Q8BZ39 (Mm), Q9ESQ4 (Rn) |
| Wikipedia | NMUR2 (Hs) |
| Natural/Endogenous Ligands |
| neuromedin S-33 {Sp: Human} |
| neuromedin S-36 {Sp: Mouse} , neuromedin S-36 {Sp: Rat} |
| neuromedin U-25 {Sp: Human} |
| neuromedin U-23 {Sp: Rat} |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 1) pIC50 for neuromedin S is determined against 50pM [125I-Tyr0]-neuromedin S 2) Agonism and pEC50 values are based on Ca2+ signaling by recombinant receptors expressed in cell lines. 3) Modified peptide ligands and non-peptide ligands have emerged that have high potency and improved pharmacokinetic features. These include compounds with NMU2 selectivity [30-32,47,51] (see General Introduction). NY0116 exhibits very slight NMU2 selectivity compared to NMU1, but interactions with other GPCRs cannot be excluded. |
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| Comments: Coupling to Gi/G0 G proteins has been identified as evidenced by inhibition of forskolin-induced cAMP accumulation [1,5,7,18,20,61]. | |
| References: 1,5,7,44,49-50,61 | |
| Tissue Distribution
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| Expression Datasets |
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| Physiological Functions Comments | |
Evidence across species (human, rat, mouse) for involvement in a range of patho-physiological aspects including:
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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1. Aiyar N, Disa J, Foley JJ, Buckley PT, Wixted WE, Pullen M, Shabon U, Dul E, Szekeres PG, Elshourbagy NA et al.. (2004) Radioligand binding and functional characterization of recombinant human NmU1 and NmU2 receptors stably expressed in clonal human embryonic kidney-293 cells. Pharmacology, 72 (1): 33-41. [PMID:15292653]
2. Bechtold DA, Ivanov TR, Luckman SM. (2009) Appetite-modifying actions of pro-neuromedin U-derived peptides. Am J Physiol Endocrinol Metab, 297 (2): E545-51. [PMID:19531638]
3. Bhattacharyya S, Luan J, Farooqi IS, Keogh J, Montague C, Brennand J, Jorde L, Wareham NJ, O'Rahilly S. (2004) Studies of the neuromedin U-2 receptor gene in human obesity: evidence for the existence of two ancestral forms of the receptor. J Endocrinol, 183 (1): 115-20. [PMID:15525579]
4. Brighton PJ, Szekeres PG, Willars GB. (2004) Neuromedin U and its receptors: structure, function, and physiological roles. Pharmacol Rev, 56 (2): 231-48. [PMID:15169928]
5. Brighton PJ, Szekeres PG, Wise A, Willars GB. (2004) Signaling and ligand binding by recombinant neuromedin U receptors: evidence for dual coupling to Galphaq/11 and Galphai and an irreversible ligand-receptor interaction. Mol Pharmacol, 66 (6): 1544-56. [PMID:15331768]
6. Cao CQ, Yu XH, Dray A, Filosa A, Perkins MN. (2003) A pro-nociceptive role of neuromedin U in adult mice. Pain, 104 (3): 609-16. [PMID:12927633]
7. Chen RX, Liu F, Li Y, Liu GA. (2012) Neuromedin S increases L-type Ca(2+) channel currents through G(i)α-protein and phospholipase C-dependent novel protein kinase C delta pathway in adult rat ventricular myocytes. Cell Physiol Biochem, 30 (3): 618-30. [PMID:22832358]
8. 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 (28): 21068-74. [PMID:10783389]
9. Fukue Y, Sato T, Teranishi H, Hanada R, Takahashi T, Nakashima Y, Kojima M. (2006) Regulation of gonadotropin secretion and puberty onset by neuromedin U. FEBS Lett, 580 (14): 3485-8. [PMID:16716306]
10. Funes S, Hedrick JA, Yang S, Shan L, Bayne M, Monsma Jr FJ, Gustafson EL. (2002) Cloning and characterization of murine neuromedin U receptors. Peptides, 23 (9): 1607-15. [PMID:12217421]
11. Gartlon J, Szekeres P, Pullen M, Sarau HM, Aiyar N, Shabon U, Michalovich D, Steplewski K, Ellis C, Elshourbagy N et al.. (2004) Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats. Psychopharmacology (Berl.), 177 (1-2): 1-14. [PMID:15205870]
12. Graham ES, Littlewood P, Turnbull Y, Mercer JG, Morgan PJ, Barrett P. (2005) Neuromedin-U is regulated by the circadian clock in the SCN of the mouse. Eur J Neurosci, 21 (3): 814-9. [PMID:15733101]
13. 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 (5): 1165-73. [PMID:14622096]
14. Guan XM, Yu H, Jiang Q, Van Der Ploeg LH, Liu Q. (2001) Distribution of neuromedin U receptor subtype 2 mRNA in the rat brain. Brain Res Gene Expr Patterns, 1 (1): 1-4. [PMID:15018811]
15. Hanada R, Nakazato M, Murakami N, Sakihara S, Yoshimatsu H, Toshinai K, Hanada T, Suda T, Kangawa K, Matsukura S et al.. (2001) A role for neuromedin U in stress response. Biochem Biophys Res Commun, 289 (1): 225-8. [PMID:11708803]
16. Hanada R, Teranishi H, Pearson JT, Kurokawa M, Hosoda H, Fukushima N, Fukue Y, Serino R, Fujihara H, Ueta Y et al.. (2004) Neuromedin U has a novel anorexigenic effect independent of the leptin signaling pathway. Nat Med, 10 (10): 1067-73. [PMID:15448684]
17. Hanada T, Date Y, Shimbara T, Sakihara S, Murakami N, Hayashi Y, Kanai Y, Suda T, Kangawa K, Nakazato M. (2003) Central actions of neuromedin U via corticotropin-releasing hormone. Biochem Biophys Res Commun, 311 (4): 954-8. [PMID:14623274]
18. Hosoya M, Moriya T, Kawamata Y, Ohkubo S, Fujii R, Matsui H, Shintani Y, Fukusumi S, Habata Y, Hinuma S et al.. (2000) Identification and functional characterization of a novel subtype of neuromedin U receptor. J Biol Chem, 275 (38): 29528-32. [PMID:10887190]
19. Howard AD, Wang R, Pong SS, Mellin TN, Strack A, Guan XM, Zeng Z, Williams Jr DL, Feighner SD, Nunes CN et al.. (2000) Identification of receptors for neuromedin U and its role in feeding. Nature, 406 (6791): 70-4. [PMID:10894543]
20. Hsu SH, Luo CW. (2007) Molecular dissection of G protein preference using Gsalpha chimeras reveals novel ligand signaling of GPCRs. Am J Physiol Endocrinol Metab, 293 (4): E1021-9. [PMID:17652154]
21. Ingallinella P, Peier AM, Pocai A, Marco AD, Desai K, Zytko K, Qian Y, Du X, Cellucci A, Monteagudo E et al.. (2012) PEGylation of Neuromedin U yields a promising candidate for the treatment of obesity and diabetes. Bioorg Med Chem, 20 (15): 4751-9. [PMID:22771182]
22. Ivanov TR, Lawrence CB, Stanley PJ, Luckman SM. (2002) Evaluation of neuromedin U actions in energy homeostasis and pituitary function. Endocrinology, 143 (10): 3813-21. [PMID:12239092]
23. Jethwa PH, Small CJ, Smith KL, Seth A, Darch SJ, Abbott CR, Murphy KG, Todd JF, Ghatei MA, Bloom SR. (2005) Neuromedin U has a physiological role in the regulation of food intake and partially mediates the effects of leptin. Am J Physiol Endocrinol Metab, 289 (2): E301-5. [PMID:16014357]
24. Jethwa PH, Smith KL, Small CJ, Abbott CR, Darch SJ, Murphy KG, Seth A, Semjonous NM, Patel SR, Todd JF et al.. (2006) Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat. Endocrinology, 147 (6): 2886-92. [PMID:16556758]
25. Kamisoyama H, Honda K, Saneyasu T, Sugahara K, Hasegawa S. (2007) Central administration of neuromedin U suppresses food intake in chicks. Neurosci Lett, 420 (1): 1-5. [PMID:17445984]
26. Ketterer K, Kong B, Frank D, Giese NA, Bauer A, Hoheisel J, Korc M, Kleeff J, Michalski CW, Friess H. (2009) Neuromedin U is overexpressed in pancreatic cancer and increases invasiveness via the hepatocyte growth factor c-Met pathway. Cancer Lett, 277 (1): 72-81. [PMID:19118941]
27. 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 (2): 435-8. [PMID:11027493]
28. Kowalski TJ, Spar BD, Markowitz L, Maguire M, Golovko A, Yang S, Farley C, Cook JA, Tetzloff G, Hoos L et al.. (2005) Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice. J Endocrinol, 185 (1): 151-64. [PMID:15817836]
29. Liu JJ, Payza K, Huang J, Liu R, Chen T, Coupal M, Laird JM, Cao CQ, Butterworth J, Lapointe S et al.. (2009) Discovery and pharmacological characterization of a small-molecule antagonist at neuromedin U receptor NMUR2. J Pharmacol Exp Ther, 330 (1): 268-75. [PMID:19369576]
30. Ma ML, Li M, Gou JJ, Ruan TY, Jin HS, Zhang LH, Wu LC, Li XY, Hu YH, Wen K et al.. (2014) Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor. Bioorg Med Chem, 22 (21): 6117-23. [PMID:25262941]
31. Marsh DJ, Pessi A, Bednarek MA, Bianchi E, Ingallinella P, Peier AM. (2011) Neuromedin U Receptor Agonists and Uses Thereof. Patent number: EP1999143 B1. Priority date: 20/03/2006. Publication date: 13/07/2011.
32. Meng T, Su HR, Binkert C, Fischli W, Zhou L, Shen JK, Wang MW. (2008) Identification of non-peptidic neuromedin U receptor modulators by a robust homogeneous screening assay. Acta Pharmacol Sin, 29 (4): 517-27. [PMID:18358099]
33. Micewicz ED, Bahattab OS, Willars GB, Waring AJ, Navab M, Whitelegge JP, McBride WH, Ruchala P. (2015) Small lipidated anti-obesity compounds derived from neuromedin U. Eur J Med Chem, 101: 616-26. [PMID:26204509]
34. 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 (2): 325-35. [PMID:15635449]
35. Nakahara K, Hanada R, Murakami N, Teranishi H, Ohgusu H, Fukushima N, Moriyama M, Ida T, Kangawa K, Kojima M. (2004) The gut-brain peptide neuromedin U is involved in the mammalian circadian oscillator system. Biochem Biophys Res Commun, 318 (1): 156-61. [PMID:15110767]
36. Nakahara K, Kojima M, Hanada R, Egi Y, Ida T, Miyazato M, Kangawa K, Murakami N. (2004) Neuromedin U is involved in nociceptive reflexes and adaptation to environmental stimuli in mice. Biochem Biophys Res Commun, 323 (2): 615-20. [PMID:15369794]
37. 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 (1): 191-4. [PMID:11027662]
38. Nandha KA, Benito-Orfila MA, Jamal H, Akinsanya KO, Bloom SR, Smith DM. (1999) Effect of steroids and the estrous cycle on uterine neuromedin U receptor expression. Peptides, 20 (10): 1203-9. [PMID:10573292]
39. Neuner P, Peier AM, Talamo F, Ingallinella P, Lahm A, Barbato G, Di Marco A, Desai K, Zytko K, Qian Y et al.. (2014) Development of a neuromedin U-human serum albumin conjugate as a long-acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide. J Pept Sci, 20 (1): 7-19. [PMID:24222478]
40. Niimi M, Murao K, Taminato T. (2001) Central administration of neuromedin U activates neurons in ventrobasal hypothalamus and brainstem. Endocrine, 16: 201-206. [PMID:11954664]
41. Ozaki Y, Onaka T, Nakazato M, Saito J, Kanemoto K, Matsumoto T, Ueta Y. (2002) Centrally administered neuromedin U activates neurosecretion and induction of c-fos messenger ribonucleic acid in the paraventricular and supraoptic nuclei of rat. Endocrinology, 143 (11): 4320-9. [PMID:12399428]
42. Peier A, Kosinski J, Cox-York K, Qian Y, Desai K, Feng Y, Trivedi P, Hastings N, Marsh DJ. (2009) The antiobesity effects of centrally administered neuromedin U and neuromedin S are mediated predominantly by the neuromedin U receptor 2 (NMUR2). Endocrinology, 150 (7): 3101-9. [PMID:19324999]
43. Quan H, Funabashi T, Furuta M, Kimura F. (2003) Effects of neuromedin U on the pulsatile LH secretion in ovariectomized rats in association with feeding conditions. Biochem Biophys Res Commun, 311 (3): 721-7. [PMID:14623332]
44. Raddatz R, Wilson AE, Artymyshyn R, Bonini JA, Borowsky B, Boteju LW, Zhou S, Kouranova EV, Nagorny R, Guevarra MS et al.. (2000) Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system. J Biol Chem, 275 (42): 32452-9. [PMID:10899166]
45. Rucinski M, Ziolkowska A, Tyczewska M, Szyszka M, Malendowicz LK. (2008) Neuromedin U directly stimulates growth of cultured rat calvarial osteoblast-like cells acting via the NMU receptor 2 isoform. Int J Mol Med, 22 (3): 363-8. [PMID:18698496]
46. Sakamoto T, Mori K, Miyazato M, Kangawa K, Sameshima H, Nakahara K, Murakami N. (2008) Involvement of neuromedin S in the oxytocin release response to suckling stimulus. Biochem Biophys Res Commun, 375 (1): 49-53. [PMID:18675786]
47. Sampson CM, Kasper JM, Felsing DE, Raval SR, Ye N, Wang P, Patrikeev I, Rytting E, Zhou J, Allen JA et al.. (2018) Small-Molecule Neuromedin U Receptor 2 Agonists Suppress Food Intake and Decrease Visceral Fat in Animal Models. Pharmacol Res Perspect, 6 (5): e00425. [PMID:30151213]
48. Sato S, Hanada R, Kimura A, Abe T, Matsumoto T, Iwasaki M, Inose H, Ida T, Mieda M, Takeuchi Y et al.. (2007) Central control of bone remodeling by neuromedin U. Nat Med, 13 (10): 1234-40. [PMID:17873881]
49. Shan L, Qiao X, Crona JH, Behan J, Wang S, Laz T, Bayne M, Gustafson EL, Monsma Jr FJ, Hedrick JA. (2000) Identification of a novel neuromedin U receptor subtype expressed in the central nervous system. J Biol Chem, 275 (50): 39482-6. [PMID:11010960]
50. Szekeres PG, Muir AI, Spinage LD, Miller JE, Butler SI, Smith A, Rennie GI, Murdock PR, Fitzgerald LR, Wu Hl et al.. (2000) Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3. J Biol Chem, 275 (27): 20247-50. [PMID:10811630]
51. Takayama K, Mori K, Taketa K, Taguchi A, Yakushiji F, Minamino N, Miyazato M, Kangawa K, Hayashi Y. (2014) Discovery of selective hexapeptide agonists to human neuromedin u receptors types 1 and 2. J Med Chem, 57 (15): 6583-93. [PMID:24999562]
52. Takayama K, Mori K, Tanaka A, Sasaki Y, Sohma Y, Taguchi A, Taniguchi A, Sakane T, Yamamoto A, Miyazato M et al.. (2020) A chemically stable peptide agonist to neuromedin U receptor type 2. Bioorg Med Chem, 28 (10): 115454. [PMID:32247748]
53. Thompson EL, Murphy KG, Todd JF, Martin NM, Small CJ, Ghatei MA, Bloom SR. (2004) Chronic administration of NMU into the paraventricular nucleus stimulates the HPA axis but does not influence food intake or body weight. Biochem Biophys Res Commun, 323 (1): 65-71. [PMID:15351702]
54. Torres R, Croll SD, Vercollone J, Reinhardt J, Griffiths J, Zabski S, Anderson KD, Adams NC, Gowen L, Sleeman MW et al.. (2007) Mice genetically deficient in neuromedin U receptor 2, but not neuromedin U receptor 1, have impaired nociceptive responses. Pain, 130 (3): 267-78. [PMID:17379411]
55. Trejter M, Neri G, Rucinski M, Majchrzak M, Nussdorfer GG, Malendowicz LK. (2008) Neuromedin-U stimulates enucleation-induced adrenocortical regeneration in the rat. Int J Mol Med, 21 (6): 683-7. [PMID:18506360]
56. Vigo E, Roa J, López M, Castellano JM, Fernandez-Fernandez R, Navarro VM, Pineda R, Aguilar E, Diéguez C, Pinilla L et al.. (2007) Neuromedin s as novel putative regulator of luteinizing hormone secretion. Endocrinology, 148 (2): 813-23. [PMID:17110433]
57. Wren AM, Small CJ, Abbott CR, Jethwa PH, Kennedy AR, Murphy KG, Stanley SA, Zollner AN, Ghatei MA, Bloom SR. (2002) Hypothalamic actions of neuromedin U. Endocrinology, 143 (11): 4227-34. [PMID:12399416]
58. Yang G, Su J, Yao Y, Lei Z, Zhang G, Li X. (2010) The regulatory mechanism of neuromedin S on luteinizing hormone in pigs. Anim Reprod Sci, 122 (3-4): 367-74. [PMID:21071159]
59. 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 (2): 467-74. [PMID:12890516]
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