Neuromedin U receptors (provisional nomenclature) are activated by the endogenous 25 amino acid peptide neuromedin U (NMU-25, NMU), a peptide originally isolated from pig spinal cord [9]. In humans, NMU-25 appears to be the sole product of a precursor (ENSG00000109255) showing a broad tissue distribution, but which is expressed at highest levels in the upper gastrointestinal tract, CNS, bone marrow and fetal liver. Much shorter versions of NMU are found in some species, but not human, and are derived at least in some instances from the proteolytic cleavage of the longer NMU. Despite species differences in NMU structure, the C-terminal region (particularly the C-terminal pentapeptide) is highly conserved and contains biological activity. Neuromedin S (NMS-33) has also been identified as an endogenous agonist [10]. NMS-33 is a 36 amino-acid product of a precursor protein derived from a single gene (ENSG00000204640) and contains an amidated C-terminal heptapeptide identical to NMU. NMS-33 appears to activate NMU receptors with equivalent potency to NMU-25.

NMU1 and NMU2 couple predominantly to G_q/11 although there is evidence of good coupling to G_i/o [1,3,5]. NMU1 and NMU2 can be labelled with [¹²⁵I]-NMU and [¹²⁵I]-NMS (of various species, e.g. [8]), BODIPY^® TMR-NMU or Cy3B-NMU-8 [1]. A range of radiolabelled (¹²⁵I-), fluorescently labelled (e.g. Cy3, Cy5, rhodamine and FAM) and biotin labelled versions of NMU-25 and NMS-33 are now commercially available.

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]

Budhiraja, S; Chugh, A. (2009) Neuromedin U: physiology, pharmacology and therapeutic potential. Fundam Clin Pharmacol, 23 (2): 149-57. [PMID:19645813]

Mitchell, JD; Maguire, JJ; Davenport, AP. (2009) Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S. Br. J. Pharmacol., 158 (1): 87-103. [PMID:19519756]

Novak, CM. (2009) Neuromedin S and U. Endocrinology, 150 (7): 2985-7. [PMID:19549882]

1. 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]

2. Hedrick, J. A., Morse, K., Shan, L., Qiao, X., Pang, L., Wang, S., Laz, T., Gustafson, E. L., Bayne, M. and Monsma, F. J. Jr. (2000) Identification of a human gastrointestinal tract and immune system receptor for the peptide neuromedin U. Mol. Pharmacol., 58: 870-875. [PMID:10999960]

3. Hosoya, M., Moriya, T., Kawamata, Y., Ohkubo, S., Fujii, R., Matsui, H., Shintani, Y., Fukusumi, S., Habata, Y., Hinuma, S., Onda, H., Nishimura, O. and Fujino, M. (2000) Identification and functional characterization of a novel subtype of neuromedin U receptor. J. Biol. Chem., 275: 29528-29532. [PMID:10887190]

4. Howard, A. D., Wang, R., Pong, S. S., Mellin, T. N., Strack, A., Guan, X. M., Zeng, Z., Williams, D. L. Jr., 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. and Liu, Q. (2000) Identification of receptors for neuromedin U and its role in feeding. Nature, 406: 70-74. [PMID:10894543]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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 (3): 1078-85. [PMID:3839674]

10. Mori, K., Miyazato, M., Ida, T., Murakami, N., Serino, R., Ueta, Y., Kojima, M. and Kangawa, K. (2005) Identification of neuromedin S and its possible role in the mammalian circadian oscillator system. EMBO J, 24: 325-335. [PMID:15635449]

11. 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. and 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. [PMID:10899166]

12. Shan, L., Qiao, X., Crona, J. H., Behan, J., Wang, S., Laz, T., Bayne, M., Gustafson, E. L., Monsma, F. J. Jr. and Hedrick, J. A. (2000) Identification of a novel neuromedin U receptor subtype expressed in the central nervous system. J. Biol. Chem., 275: 39482-39486. [PMID:11010960]

13. 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. and Chambers, J. K. (2000) Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3. J. Biol. Chem., 275: 20247-20250. [PMID:10811630]

14. Tan, C. P., McKee, K. K., Liu, Q., Palyha, O. C., Feighner, S. D., Hreniuk, D. L., Smith, R. G. and Howard, A. D. (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. [PMID:9782091]

15. 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]