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NMU1 receptor

Family: Neuromedin U receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 403 2q37.1 NMUR1 neuromedin U receptor 1 3,26,30
Mouse 7 406 1 D1 Nmur1 neuromedin U receptor 1 30
Rat 7 402 9q35 Nmur1 neuromedin U receptor 1 12
Structural Information Comments
For human NMU1, sequences encoding both 403 and 426 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 [3].
Previous and Unofficial Names
Names References
FM-3 11-12,28,30
GPR66 11,16,28
NmU-R1 28
G protein-coupled receptor FM-3
neuromedin U receptor 1
NMU1R
FM3 29
SNORF62 26
Database Links
Ensembl ENSG00000171596 (Hs), ENSMUSG00000026237 (Mm), ENSRNOG00000018521 (Rn)
Entrez Gene 10316 (Hs), 14767 (Mm), 65276 (Rn)
GeneCards NMUR1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Nmur1 (Mm)
HomoloGene 68501 (Hs)
Human Protein Reference Database 16039 (Hs)
InterPro Q9HB89 (Hs), O55040 (Mm), Q9JIB2 (Rn)
KEGG Gene hsa:10316 (Hs), mmu:14767 (Mm), rno:65276 (Rn)
OMIM 604153 (Hs)
PharmGKB Gene PA28910 (Hs)
PhosphoSitePlus Q9HB89 (Hs), O55040 (Mm), Q9JJI5 (Rn)
Protein Ontology (PRO) PRO:000001618 (Hs)
RefSeq Nucleotide NM_006056 (Hs), NM_010341 (Mm), NM_023100 (Rn)
RefSeq Protein NP_006047 (Hs), NP_034471 (Mm), NP_075588 (Rn)
TreeFam ENSG00000171596 (Hs), ENSMUSG00000026237 (Mm), ENSRNOG00000018521 (Rn)
UniGene Hs. 471619 (Hs)
UniProt Q9HB89 (Hs), O55040 (Mm), Q9JIB2 (Rn)
Wikipedia NMU1 receptor
Neuromedin U receptors
Search for 3D structures on the PDB
Search by keyword: Neuromedin U receptors NMU1 receptor Search by accession number: Q9JIB2, Q9HB89, O55040
Natural/Endogenous Ligand(s)
neuromedin S-33 {Sp: Human}
neuromedin S-36 {Sp: Mouse} , neuromedin S-36 {Sp: Rat}
neuromedin U-23 {Sp: Rat} , neuromedin U-23 {Sp: Mouse}
neuromedin U-25 {Sp: Human}
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]neuromedin U-25 (human) Hs Agonist 9.9 – 10.1 pKd 1,4
[125I]neuromedin U-23 (rat) Hs Agonist 9.1 – 9.5 pKd 12,26
[125I]neuromedin U-8 (pig) Hs Agonist 8.6 pKd 26
neuromedin U-23 {Sp: Rat} Hs Agonist 10.1 pKi 1
neuromedin U-25 {Sp: Pig} Hs Agonist 9.6 pKi 1
neuromedin U-25 {Sp: Human} Hs Agonist 9.5 pKi 1
neuromedin U-8 {Sp: Pig} Hs Agonist 8.8 pKi 1
neuromedin U-8 {Sp: Dog} Hs Agonist 8.5 pKi 1
neuromedin S-33 {Sp: Human} Hs Full agonist 10.2 pEC50 21
neuromedin U-8 {Sp: Pig} Hs Full agonist 9.0 – 10.0 pEC50 1,12,26
neuromedin U-23 {Sp: Rat} Hs Full agonist 8.7 – 9.1 pEC50 1,12,26
neuromedin U-25 {Sp: Human} Hs Full agonist 8.4 – 9.4 pEC50 1,4,12,26
neuromedin U-25 {Sp: Pig} Hs Full agonist 8.3 – 8.9 pEC50 1,12,26
neuromedin S-33 {Sp: Human} Hs Agonist 10.0 pIC50 21
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.
Primary Transduction Mechanisms
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 [1,4].
References:  1,4,26,29
Tissue Distribution
Significant levels in adipose tissue, duodenum, jejunum, small intestine, adrenal cortex, bone marrow and testis. Moderate amounts found in spleen, stomach, lung, trachea, mammary gland, kidney, pancreas, prostate, uterus, heart and placenta. Transcripts also observed in considerable levels in human ileum smooth muscle, caecum, gallbladder, long saphenous vein and all colon segments. In the cardiovascular system, mRNA and protein are mainly in the left ventricle, coronary artery and saphenous vein.
Species:  Human
Technique:  Northern blot, quantitative PCR, in situ hybridization, Western blot.
References:  10-12,14,19,26,29
A similar pattern to that of human.
Expression in thymus, peripheral blood leukocytes (particularly B and T cells), lung, stomach, spleen, mesenteric lymphnodes, peyer's patches, spinal cord.
Some have failed to show NMUR1 expression in human and mouse brains, others have shown low levels with widespread expression. Highest levels in the cerebellum, dorsal root ganglion, hippocampus and spinal cord (levels 5-25 fold less than in periphery).
Species:  Mouse
Technique:  Northern blots, quantitative PCR, in situ hybridization
References:  7,11-12,26,29
A similar pattern to that of human.
Highest levels of mRNA in duodenum, jejunum, ileum, lung and spleen; moderate levels in femur, caecum, colon and rectum. Transcripts and protein in the medullary and cortical areas of adrenal gland. mRNA and protein in pancreatic islets.
Expressed in approximately 25% of small/medium diameter neurones within the dorsal root ganglia.
Species:  Rat
Technique:  Northern blot, quantitative PCR, in situ hybridization, Western blot.
References:  8,10,13,15,27,31-33
Expression Datasets

Click here to show/hide data

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Cells transfected with NMU1.
Species:  Human
Tissue:  CHO, HEK-293 and COS-7 cells.
Response measured:  Increase in intracellular calcium, inositol phosphate generation, inhibition of forskolin-stimulated cAMP generation, ERK activation, G-protein activation.
References:  1,4,8,11-12,16,26,29
Cells transfected with NMU1.
Species:  Mouse
Tissue:  HEK-293 cells.
Response measured:  Increase in intracellular calcium.
References:  9
Physiological Functions Comments
Evidence exists across species for involvement of NMU1 in a range of physiological aspects including:
Contraction: human ileum and urinary bladder [17], gall bladder, ascending colon and long saphenous vein [14], coronary artery, mammary artery and saphenous vein [19], rat uterus smooth muscle [18], rat stomach-fundus [2], lower esophageal sphincter and ileum [25], colon [5], mouse gall bladder, stomach-fundus, uterus, lower esophageal sphincter [25] and forestomach [6].
Stress response [27,31,33].
Inhibition of gastric acid secretion and gastric emptying [20].
Inflammatory and immunological responses [22-24].
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Nmur1tm1Lex Nmur1tm1Lex/Nmur1tm1Lex
Not Specified		 MGI:1341898  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 16474416 
Nmur1tm1Rtor|Nmur2tm1Rtor Nmur1tm1Rtor/Nmur1tm1Rtor,Nmur2tm1Rtor/Nmur2tm1Rtor
involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6NCr * C57BL/6NTac		 MGI:1341898  MGI:2441765  MP:0001973 increased thermal nociceptive threshold PMID: 17379411 
Nmur1tm1Sjab Nmur1tm1Sjab/Nmur1tm1Sjab
involves: 129P2/OlaHsd * C57BL/6		 MGI:1341898  MP:0002169 no abnormal phenotype detected PMID: 19070594 

REFERENCES

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1. Aiyar, N., Disa, J., Foley, J. J., Buckley, P. T., Wixted, W. E., Pullen, M., Shabon, U., Dul, E., Szekeres, P. G., Elshourbagy, N. A., Sarau, H. M., Appelbaum, E. and Bolaky, J. (2004) Radioligand binding and functional characterization of recombinant human NmU1 and NmU2 receptors stably expressed in clonal human embryonic kidney-293 cells. Pharmacology, 72: 33-41. [PMID:15292653]

2. Benito-Orfila, M. A., Domin, J., Nandha, K. A. and Bloom, S.R. (1991) The motor effect of neuromedin U on rat stomach in vitro. . Eur. J. Pharmacol., 193: 329-333. [PMID:2055247]

3. 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]

4. 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]

5. Brighton, PJ; Wise, A; Dass, NB; Willars, GB. (2008) Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissue. J. Pharmacol. Exp. Ther., 325 (1): 154-64. [PMID:18180374]

6. Dass, NB; Bassil, AK; North-Laidler, VJ; Morrow, R; Aziz, E; Tuladhar, BR; Sanger, GJ. (2007) Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation. Br. J. Pharmacol., 150 (4): 502-8. [PMID:17211455]

7. Domin, J., Al Madani, A. M., Desperbasques, M., Bishop, A. E., Polak, J. M. and Bloom, S. R. (1990) Neuromedin U-like immunoreactivity in the thyroid gland of the rat. Cell Tissue Res., 260: 131-135. [PMID:2340578]

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. Funes, S., Hedrick, J. A., Yang, S., Shan, L., Bayne, M., Monsma, F. J. Jr. and Gustafson, E. L. (2002) Cloning and characterization of murine neuromedin U receptors. Peptides, 23: 1607-1615. [PMID:12217421]

10. 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]

11. 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]

12. 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]

13. 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]

14. Jones, NA; Morton, MF; Prendergast, CE; Powell, GL; Shankley, NP; Hollingsworth, SJ. (2006) Neuromedin U stimulates contraction of human long saphenous vein and gastrointestinal smooth muscle in vitro. Regul. Pept., 136 (1-3): 109-16. [PMID:16782214]

15. Kaczmarek, P; Malendowicz, LK; Pruszynska-Oszmalek, E; Wojciechowicz, T; Szczepankiewicz, D; Szkudelski, T; Nowak, KW. (2006) 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., 18 (5): 951-5. [PMID:17016626]

16. 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]

17. Maggi, C. A., Patacchini, R., Giuliani, S., Turini, D., Barbanti, G., Rovero, P. and Meli, A. (1990) Motor response of the human isolated small intestine and urinary bladder to porcine neuromedin U-8. Br. J. Pharmacol., 99: 186-188. [PMID:2331570]

18. 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]

19. Mitchell, JD; Maguire, JJ; Kuc, RE; Davenport, AP. (2009) Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system. Cardiovasc. Res., 81 (2): 353-61. [PMID:18987052]

20. Mondal, MS; Date, Y; Murakami, N; Toshinai, K; Shimbara, T; Kangawa, K; Nakazato, M. (2003) Neuromedin U acts in the central nervous system to inhibit gastric acid secretion via CRH system. Am. J. Physiol. Gastrointest. Liver Physiol., 284 (6): G963-9. [PMID:12584108]

21. 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]

22. Moriyama, M; Fukuyama, S; Inoue, H; Matsumoto, T; Sato, T; Tanaka, K; Kinjyo, I; Kano, T; Yoshimura, A; Kojima, M. (2006) The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia. Am. J. Physiol. Lung Cell Mol. Physiol., 290 (5): L971-7. [PMID:16373672]

23. Moriyama, M; Matsukawa, A; Kudoh, S; Takahashi, T; Sato, T; Kano, T; Yoshimura, A; Kojima, M. (2006) The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock. Biochem. Biophys. Res. Commun., 341 (4): 1149-54. [PMID:16466693]

24. 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 (2): 217-24. [PMID:16009716]

25. Prendergast, CE; Morton, MF; Figueroa, KW; Wu, X; Shankley, NP. (2006) Species-dependent smooth muscle contraction to Neuromedin U and determination of the receptor subtypes mediating contraction using NMU1 receptor knockout mice. Br. J. Pharmacol., 147 (8): 886-96. [PMID:16474416]

26. 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]

27. Rucinski, M; Ziolkowska, A; Neri, G; Trejter, M; Zemleduch, T; Tyczewska, M; Nussdorfer, GG; Malendowicz, LK. (2007) Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat. Int. J. Mol. Med., 20 (2): 255-9. [PMID:17611645]

28. 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]

29. 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]

30. 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]

31. 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]

32. Yu, X. H., Cao, C. Q., Mennicken, F., Puma, C., Dray, A., O'Donnell, D., Ahmad, S. and Perkins, M. (2003) Pro-nociceptive effects of neuromedin U in rat. Neuroscience, 120: 467-474. [PMID:12890516]

33. Ziolkowska, A; Macchi, C; Trejter, M; Rucinski, M; Nowak, M; Nussdorfer, GG; Malendowicz, LK. (2008) Effects of neuromedin-U on immature rat adrenocortical cells: in vitro and in vivo studies. Int. J. Mol. Med., 21 (3): 303-7. [PMID:18288377]

To cite this database page, please use the following:

Gary B. Willars, Khaled Al-hosaini.
Neuromedin U receptors: NMU1 receptor. Last modified on 04/03/2013. Accessed on 24/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=298.


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