Neuromedin U receptors: Introduction


Neuromedin U (NmU) was first isolated from porcine spinal cord in 1985 and named for its potent contractile activity on the rat uterus [78]. Two molecular forms were purified; the icosapentapeptide (NmU-25) and an octapeptide (NmU-8) identical to the C-terminal of NmU-25 [78]. Both forms are biologically active, stimulating contraction of rat uterus in vitro and causing potent vasoconstriction in rats and dogs [29,78,117]. NmU has since been fully sequenced in several species including rat [20,77], dog [95], rabbit [56], frog [22,63,108], chicken [19,96], guinea pig [88], human [5], Japanese quail [114] and goldfish [72]. Most of the NmU analogues that have been isolated are icosapentapeptides with the exception of rat NmU-23 [16], tree-frog NmU-23 [108], Chinese toad NmU-17 [63], goldfish NmU-21 and NmU-38 (also has NmU-25) [72] and nonapeptides (NmU-9) from chicken [96] (also has NmU-25) and guinea pig [88]. In pig and dog, both NmU-25 and NmU-8 are found, the latter most likely being generated from the former through proteolysis at a dibasic cleavage site (Arg16-Arg17) [78,95]. A comparison of the amino acid sequences of NmU reveals that the peptide has been remarkably conserved throughout evolution [10]. This degree of conservation, particularly of the amidated carboxyl-terminus is indicative of the importance of this for biological activity [21,40,78,107].

In addition to the potent contractile effect of NmU on rat uterus, several studies have demonstrated the tissue and species specificity of NmU contractile effects [7,11,52,78-79,99,134]. With time it has become clear that NmU is involved in a plethora of patho-physiological actions including: the regulation of blood pressure and regional blood flow [15,29,78-79,102,117,126,134]; the control of food intake, temperature and locomotor activity [6,9,23,36-37,43,47-48,61-62,91,135,140]; antidepressant and anxiolytic effects [125,127]; regulation of the stress response and the hypothalamic-pituitary-adrenal axis [30,49,61,68-69,129]; gastric emptying, acid secretion and ion transport [17,81]; nociception [12,22,92,130,139-140]; bone formation and remodelling [32,110]; insulin secretion and glucose homeostasis [54-55,98]; circadian rhythm [1,33,90,92]; inflammation, immunological responses and production of antibodies involved in arthritis [41,51,85-87,104]; addictive-type behaviours associated with food, drugs and alcohol [50,58-59,66,74,115,131-132]; complications associated with obesity such as non-alcoholic steatohepatitis [128]; cancer [2,24,28,38-39,60,64-65,103,113,119,136-137], and resistance to alectinib in the treatment of non-small cell lung cancer [138]. Whether relevant amounts of NmU enter the circulation to deliver remote effects is unclear although evidence suggests that NmU does not function as a circulating hormone. Transport of NmU into the brain across the blood-brain barrier has, however, been reported, at least raising the possibility of other mechanisms of action [31]. Indeed the half-life of any circulating NmU is less than 5 min [98]. Interestingly, thrombin has recently been reported as a key enzyme involved in the degradation of NmU in serum, hydrolysing an arginine-asparagine bond in the C-terminus [123]. The instability of circulating NmU, including exogenous NmU and related peptides has driven the search for more stable analogues or alternative agonists that might provide therapeutic potential.

More recently, the neuropeptide neuromedin S (NmS) has been identified as an endogeneous ligand for the same receptors that are responsible for mediating the effects of NmU [83]. NmS has also been identified in a number of species including man, rat, mouse and toad [13,83]. Peptides found in these species are of similar length (33-36 amino acids) with the exception of a 17 amino acid version found alongside a 33 amino acid version in toad [13]. The C-terminal heptapeptide of NmS is identical to that of mammalian forms of NmU and these peptides bind to the same receptors with similar affinity. Indeed, this heptapeptide is crucial for biological activity with even single amino acid substitutions in NmU-8 reducing functional effects [26,40]. Furthermore, amidation of the C-terminal asparagine is crucial for activity [10]. Despite structural similarities, NmS is not a splice variant of NmU, with the genes being located on different chromosomes [83-84]. Unlike NmU, which shows higher expression in the gastrointestinal tract than brain [5,118], with the notable exception of testes and spleen [27,82-83], NmS is mainly expressed in the central nervous system (CNS), particularly in the suprachiasmatic nucleus (SCN) of the hypothalamus (hence NmS), the site of the master circadian pacemaker in mammals [83]. Indeed, intracerebroventricular administration of NmS induces phase shifts in circadian rhythm of locomotor activity [83]. In addition, central administration of NmS inhibits food intake more potently and for longer than NmU [44,80,91]. NmS has also been found to potentiate the stress response and activate the hypothalamic-pituitary-adrenal axis [53], inhibit gastric emptying [4], contract human saphenous vein and chicken rectum smooth muscle [79,83], increase plasma levels of oxytocin [106], increase luteinizing hormone secretion [133] and potentially play a more important role in thermoregulation than NmU [89].

Although the precise pathophysiological roles of NmU and NmS perhaps remain to be fully defined, a major role for NmU in the regulation of food intake and energy balance are further supported by the phenotypes of mice in which NmU has either been knocked-out or overexpressed. Knockout mice have increased body weight and adiposity, hyperphagia, and decreased locomotor activity and energy expenditure [36]. In contrast, overexpression of NmU results in mice that are hypophagic, lighter, with reduced somatic and liver fat and improved insulin sensitivity [62]. Interestingly, a number of polymorphic variants of NmU have also been associated with childhood and adult obesity [35].


Two previously orphan Family A, GPCRs, FM-3 (GPR66, SNORF62) and FM-4 (TGR-1, SNORF72) were identified as specific and functional receptors for NmU and have subsequently been designated NMU1 and NMU2 respectively [3,112]. Well before the molecular nature of the receptors had been identified, binding sites for NmU had been characterized. Thus, studies demonstrated saturable, specific and reversible binding of 125I labelled rat NmU to membranes prepared from rat uterus that was dependent on time, temperature and pH [93]. However, in 1998, FM-3, was cloned from human and murine cDNA libraries due to its homology with the growth hormone secretagogue receptor (ghrelin receptor; 33% homology) and the neurotensin receptor (29% homology) [124]. Cloning enabled a subsequent reverse pharmacological approach that lead to the identification of NmU as its natural ligand [25,43,61,101,118]. NmU binds to and activates human FM-3 (NMU1) with sub-nanomolar affinity and potency respectively. Extracts from rat tissue were also found to contain a natural ligand for FM-3, with the brain and small intestine being most active and allowing rat NmU-23 to be purified chromatographically [77]. Screening of potential ligands at FM-3 found that only the various forms of NmU peptides provided potent activation. Peptides that show some similarity to NmU including the neuromedins B, C, K, and N, as well as neurotensin, ghrelin, motilin, vasoactive intestinal polypeptide and pancreatic polypeptide were inactive [61,101,118]. A BLAST search of the GenBankTM genomic database using the NMU1 cDNA sequence revealed a human genomic fragment encoding a GPCR that was approximately 50% homologous to NMU1, previously known as FM-4 but now designated NMU2 [43]. NMU2 has been cloned from human, rat and mouse [26,42-43,101,111,124]. Both NMU1 (FM-3) and NMU2 (FM-4) reportedly have significant abilities to distinguish between different forms of NmU, and have species and tissue selectivity in the biological actions of NmU [18,99,134].

Both receptors exhibit many characteristics of Family A GPCRs, having the predicted seven-transmembrane helices and an ERY motif in the place of the conserved E/DRY motif at the junction of the third transmembrane domain and beginning of the second intracellular loop. In Family A GPCRs this is considered to regulate ligand binding and G-protein coupling [105,116]. There are also two cysteine residues present in the extracellular domain of both receptors that may allow the formation of a disulfide bridge to maintain protein folding, ligand binding and a stable conformation [116]. Amino acid sequence similarity between NMU1 and NMU2 is mainly confined to the transmembrane domains. Both receptors have putative phosphorylation sites within their intracellular domains [10] and NMU2 is phosphorylated in a recombinant system following activation with either NmU or NmS [100]. More recently a truncated version of NMU2 has been identified in a human ovarian cDNA. Data suggest that this is expressed at the cell surface as a six transmembrane protein. Although not directly responsive to NMU ligands, this truncated construct reportedly forms heterodimers with either NMU1 or NMU2 to attenuate signalling by reducing ligand binding [64].


The gene for human NMU1 is localised to chromosome 2q37.1 and encoded by two exons [111]. NMU1 has been identified as both a 403 amino acid protein [124] and as a longer version with a 23 amino acid extended N-terminus, suggesting translation initiation from an in-frame, upstream AUG [101]. It is difficult to predict if one or both forms are expressed but the shorter form seems to have a stronger Kozak sequence and is more similar to the mouse orthologue [10]. This would give human (h) NMU1 a molecular mass of 44979 Da.

The mRNA for hNMU1 is expressed in a wide variety of tissues. In particularly the small intestines (in goblet cells in the ileum), adipose tissue, duodenum and jejunum, however mRNA is present at relatively high levels in the pancreas, stomach, testis, adrenal cortex, heart, spleen, pancreas, lung, trachea, mammary gland, bone marrow, smooth muscle and endothelial cells of cardiovascular tissues and peripheral blood leucocytes (particularly T and NK cells) [30,41,43,52,79,101,118]. A similar distribution pattern exists in the rat with highest levels in duodenum, jejunum, ileum, lung, femur and spleen [25,30]. NMU1 mRNA expression is also found in approximately 25% of the small/medium diameter neurones within the dorsal root ganglia [139]. There is relatively low or negligible expression of NMU1 in human or rodent brain [26,43].

Mice with knockout of NMU1 appear normal with respect to fertility, nociception, anatomy, behaviour and metabolism [97,130]. However, although acute and chronic peripheral administration of NmU reduces food intake and body weight in lean and diet-induced obese mice, these effects were absent in NMU1 knockout mice (NMU1-/-) [98]. Further, although NmU administration also increases plasma levels of glucagon-like peptide 1 and PYY, the anorectic action of NmU is independent of signaling by either of these peptides or indeed on leptin signaling. Although NMU2 mediates central anorectic actions of NmU (see below), these data clearly highlight a role for NMU1 in peripheral anorectic actions of the peptide, which are at least in part dependent on vagal innervation of the abdomen [98].


The gene for human NMU2 has been localised to chromosome 5q33.1. The genomic structure of NMU2 differs significantly from that of NMU1, in that the predicted open reading frame is encoded on four rather than two exons [111]. Two forms of human NMU2 have also been reported that differ in their initiating methionine; a 415 amino acid form [101,111] and a 412 amino acid form [42-43] with evidence perhaps being a little stronger for the shorter form [10], which has a predicted molecular mass of 47450 Da. 

In humans, NMU2 mRNA is confined predominantly to specific regions within the brain, with the greatest expression observed in the substantia nigra, medulla oblongata, pontine reticular formation, spinal cord and thalamus [42-43,101,111]. Moderate to high levels are also present in the indusium griseum, septohippocampal nucleus, vascular organ of the lamina terminalis, hypothalamic paraventricular nucleus, CA1 region of the hippocampus, parafasicular thalamic nucleus, dorsal raphe nucleus and along the ventral wall of the third ventricle in the hypothalamus [43]. Peripherally, the highest level is found in testis [101,111]. More recently, NMU2 mRNA has been found at much higher levels than NMU1 mRNA in human pancreatic cancer cell-lines and a pancreatic ductal adenocarcinoma [60]. In rat CNS, the hypothalamus has the highest NMU2 mRNA level, mainly in the wall of the third ventricle with moderate levels in the paraventricular nucleus and CA1 region of the hippocampus [34,43]. The high expression of NMU2 in specific regions of rat brain is also supported by a binding study in which [125I]-rNMU-23 showed high binding in the limbic system, including the hypothalamus, amygadala and hippocampus [70]. The medulla oblongata, spinal cord, hippocampus and striatum show moderate to low levels of rNMU2 mRNA [25,30,42]. In rat periphery, the highest level of rNMU2 mRNA expression is in the uterus and ovary [25,30,42]. In contrast to the high expression level of NMU2 mRNA in rat uterus, it is mostly absent in uterus of human and dog, highlighting species-dependent differences in distribution and function [101,111,134].

The distribution of NMU2, particularly its localization in hypothalamic regions that are associated with the regulation of food intake and energy balance, are entirely consistent with a role for this receptor in mediating the reductions in food intake and energy expenditure following central administration of NmU [43-44,80,91]. Furthermore, in NMU2 knockout mice, central administration of NmU or NmS no longer has the effects seen in their wild-type counterparts such as the suppression of food intake, enhanced grooming and potentiated pain responses [97,140]. Based on such data, it might be expected that knockout of NMU2 would result in a hyperphagic, obese mouse. However, this appears not to be the case and the data present a rather confused picture. Thus, although NMU2 knockout mice exhibit reduced pain sensitivity, highlighting a critical role in the central processing of pain [130,140], they appear normal with respect to food consumption, body weight, fat composition and other aspects such as anxiety and stress [23,130,140]. Indeed NMU2-/- mice have been reported as showing reduced food intake and reduced weight gain on either a regular or a high-fat diet, the latter indicating a resistance to diet-induced obesity [97]. In contrast, another study reported that female but not male NMU2-/- mice had increased body weights and adiposity but only when fed a high-fat diet, suggesting there may be sex-differences in the central requirement for NMU2 in the control of food intake, body weight and adiposity [23]. More recently, selective knockdown of NMU2 in the PVN of rats using viral delivery of RNAi demonstrated that although food intake and body weight were unaffected in rats fed a standard diet, these rats consumed more food and gained significantly more weight when fed a high-fat diet. Knockdown also resulted in binge-type feeding on a high-fat diet and a preference for higher-fat food [8]. Overall, there is, therefore, clear evidence that NMU2 mediates the effects of centrally administered NmU and NmS and emerging evidence that the role of this system may be dependent on other influencing factors such as sex and diet.

Evidence is now emerging that NmU and particularly NMU2 may have a broader role in the CNS beyond the hypothalamus. For example, a genetic overexpression screen in zebrafish demonstrated that in larva, NmU promotes activity and suppresses sleep dependent on NMU2 and corticotropin releasing hormone at the level of the brainstem [14]. NMU2 is expressed in a variety of brain areas other then the hypothalamus, including areas related to reward. Indeed, intracerebroventricularly administered NmU reduces both amphetamine- and alcohol-induced accumbal dopamine release and increases in locomotor activity, highlighting a possible role in reward-related behaviours [131-132]. In line with a role of NMU2 in such actions is also the observation of presynaptic expression on GABA neurons in the nucleus accumbens shell where it has been reported to play a role in reducing cocaine-evoked hyperactivity [58].

Novel ligands

Both the poor pharmacokinetic characteristics of administered NmU and the possibility of receptor subtype-dependent physiological roles have driven the search for compounds with improved pharmacokinetics and NMU receptor subtype selectivity. A variety of approaches have been made to improve the stability of NmU including amino acid substitution, conjugation with, for example, polyethylene glycol and bovine serum albumin, truncation and a variety of other modifications including lipidation. Such changes have generated compounds with improved stability and in vivo activity [17,45-46,57,71,73,76,94,120-122]. Additionally, non-peptide compounds including flavonoid derivatives and p-synephrine (a protoalkaloid in bitter orange) have been identified as ligands [67,75,109,141]. Amongst both the non-peptide ligands and the modified peptide ligands, a number of compounds with selectivity for NMU receptor subtypes have been reported [67,71,75,109,120-121].


Show »

1. Aizawa S, Sakata I, Nagasaka M, Higaki Y, Sakai T. (2013) Negative regulation of neuromedin U mRNA expression in the rat pars tuberalis by melatonin. PLoS ONE, 8 (7): e67118. [PMID:23843987]

2. Alevizos I, Mahadevappa M, Zhang X, Ohyama H, Kohno Y, Posner M, Gallagher GT, Varvares M, Cohen D, Kim D et al.. (2001) Oral cancer in vivo gene expression profiling assisted by laser capture microdissection and microarray analysis. Oncogene, 20 (43): 6196-204. [PMID:11593428]

3. Alexander SP, Mathie A, Peters JA. (2008) Guide to Receptors and Channels (GRAC), 3rd edition. Br. J. Pharmacol., 153 Suppl 2: S1-209. [PMID:18347570]

4. Atsuchi K, Asakawa A, Ushikai M, Ataka K, Tanaka R, Kato I, Fujimiya M, Inui A. (2010) Centrally administered neuromedin S inhibits feeding behavior and gastroduodenal motility in mice. Horm. Metab. Res., 42 (7): 535-8. [PMID:20352600]

5. Austin C, Lo G, Nandha KA, Meleagros L, Bloom SR. (1995) Cloning and characterization of the cDNA encoding the human neuromedin U (NmU) precursor: NmU expression in the human gastrointestinal tract. J. Mol. Endocrinol., 14 (2): 157-69. [PMID:7619205]

6. 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]

7. Benito-Orfila MA, Domin J, Nandha KA, Bloom SR. (1991) The motor effect of neuromedin U on rat stomach in vitro. Eur. J. Pharmacol., 193 (3): 329-33. [PMID:2055247]

8. Benzon CR, Johnson SB, McCue DL, Li D, Green TA, Hommel JD. (2014) Neuromedin U receptor 2 knockdown in the paraventricular nucleus modifies behavioral responses to obesogenic high-fat food and leads to increased body weight. Neuroscience, 258: 270-9. [PMID:24269937]

9. 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]

10. 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]

11. 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]

12. 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]

13. Chen T, Zhou M, Walker B, Harriot P, Mori K, Miyazato M, Kangawa K, Shaw C. (2006) Structural and functional analogs of the novel mammalian neuropeptide, neuromedin S (NmS), in the dermal venoms of Eurasian bombinid toads. Biochem. Biophys. Res. Commun., 345 (1): 377-84. [PMID:16682011]

14. Chiu CN, Rihel J, Lee DA, Singh C, Mosser EA, Chen S, Sapin V, Pham U, Engle J, Niles BJ et al.. (2016) A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States. Neuron, 89 (4): 842-56. [PMID:26889812]

15. Chu C, Jin Q, Kunitake T, Kato K, Nabekura T, Nakazato M, Kangawa K, Kannan H. (2002) Cardiovascular actions of central neuromedin U in conscious rats. Regul. Pept., 105 (1): 29-34. [PMID:11853869]

16. Conlon JM, Domin J, Thim L, DiMarzo V, Morris HR, Bloom SR. (1988) Primary structure of neuromedin U from the rat. J. Neurochem., 51 (3): 988-91. [PMID:3411332]

17. Dalbøge LS, Pedersen PJ, Hansen G, Fabricius K, Hansen HB, Jelsing J, Vrang N. (2015) A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents. PLoS ONE, 10 (8): e0135634. [PMID:26266945]

18. 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]

19. Domin J, Benito-Orfila MA, Nandha KA, Aitken A, Bloom SR. (1992) The purification and sequence analysis of an avian neuromedin U. Regul. Pept., 41 (1): 1-8. [PMID:1455013]

20. Domin J, Ghatei MA, Chohan P, Bloom SR. (1986) Characterization of neuromedin U like immunoreactivity in rat, porcine, guinea-pig and human tissue extracts using a specific radioimmunoassay. Biochem. Biophys. Res. Commun., 140 (3): 1127-34. [PMID:3778484]

21. Domin J, Polak JM, Bloom SR. (1988) The distribution and biological effects of neuromedins B and U. Ann. N. Y. Acad. Sci., 547: 391-403. [PMID:3239891]

22. Domin J, Yiangou YG, Spokes RA, Aitken A, Parmar KB, Chrysanthou BJ, Bloom SR. (1989) The distribution, purification, and pharmacological action of an amphibian neuromedin U. J. Biol. Chem., 264: 20881-20885. [PMID:2592357]

23. Egecioglu E, Ploj K, Xu X, Bjursell M, Salomé N, Andersson N, Ohlsson C, Taube M, Hansson C, Bohlooly-Y M et al.. (2009) Central NMU signaling in body weight and energy balance regulation: evidence from NMUR2 deletion and chronic central NMU treatment in mice. Am. J. Physiol. Endocrinol. Metab., 297 (3): E708-16. [PMID:19584200]

24. Euer NI, Kaul S, Deissler H, Möbus VJ, Zeillinger R, Weidle UH. (2005) Identification of L1CAM, Jagged2 and Neuromedin U as ovarian cancer-associated antigens. Oncol. Rep., 13 (3): 375-87. [PMID:15706405]

25. 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]

26. 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]

27. Gajjar S, Patel BM. (2017) Neuromedin: An insight into its types, receptors and therapeutic opportunities. Pharmacol Rep, 69 (3): 438-447. [PMID:28315588]

28. Garczyk S, Klotz N, Szczepanski S, Denecke B, Antonopoulos W, von Stillfried S, Knüchel R, Rose M, Dahl E. (2017) Oncogenic features of neuromedin U in breast cancer are associated with NMUR2 expression involving crosstalk with members of the WNT signaling pathway. Oncotarget, 8 (22): 36246-36265. [PMID:28423716]

29. Gardiner SM, Compton AM, Bennett T, Domin J, Bloom SR. (1990) Regional hemodynamic effects of neuromedin U in conscious rats. Am. J. Physiol., 258 (1 Pt 2): R32-8. [PMID:2301645]

30. 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]

31. Gevaert B, Wynendaele E, Stalmans S, Bracke N, D'Hondt M, Smolders I, van Eeckhaut A, De Spiegeleer B. (2016) Blood-brain barrier transport kinetics of the neuromedin peptides NMU, NMN, NMB and NT. Neuropharmacology, 107: 460-70. [PMID:27040796]

32. Gianfagna F, Cugino D, Ahrens W, Bailey ME, Bammann K, Herrmann D, Koni AC, Kourides Y, Marild S, Molnár D et al.. (2013) Understanding the links among neuromedin U gene, beta2-adrenoceptor gene and bone health: an observational study in European children. PLoS ONE, 8 (8): e70632. [PMID:23936460]

33. 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]

34. 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]

35. Hainerová I, Torekov SS, Ek J, Finková M, Borch-Johnsen K, Jørgensen T, Madsen OD, Lebl J, Hansen T, Pedersen O. (2006) Association between neuromedin U gene variants and overweight and obesity. J. Clin. Endocrinol. Metab., 91 (12): 5057-63. [PMID:16984985]

36. 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]

37. 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]

38. Harding MA, Theodorescu D. (2007) RhoGDI2: a new metastasis suppressor gene: discovery and clinical translation. Urol. Oncol., 25 (5): 401-6. [PMID:17826660]

39. Harten SK, Esteban MA, Shukla D, Ashcroft M, Maxwell PH. (2011) Inactivation of the von Hippel-Lindau tumour suppressor gene induces Neuromedin U expression in renal cancer cells. Mol. Cancer, 10: 89. [PMID:21791076]

40. Hashimoto T, Masui H, Uchida Y, Sakura N, Okimura K. (1991) Agonistic and antagonistic activities of neuromedin U-8 analogs substituted with glycine or D-amino acid on contractile activity of chicken crop smooth muscle preparations. Chem. Pharm. Bull., 39 (9): 2319-22. [PMID:1804545]

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

42. 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]

43. 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]

44. Ida T, Mori K, Miyazato M, Egi Y, Abe S, Nakahara K, Nishihara M, Kangawa K, Murakami N. (2005) Neuromedin s is a novel anorexigenic hormone. Endocrinology, 146 (10): 4217-23. [PMID:15976061]

45. 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]

46. Inooka H, Sakamoto K, Shinohara T, Masuda Y, Terada M, Kumano S, Yokoyama K, Noguchi J, Nishizawa N, Kamiguchi H et al.. (2017) A PEGylated analog of short-length Neuromedin U with potent anorectic and anti-obesity effects. Bioorg. Med. Chem., 25 (8): 2307-2312. [PMID:28291683]

47. 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]

48. 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]

49. 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]

50. Johnson C, Drgon T, Liu QR, Walther D, Edenberg H, Rice J, Foroud T, Uhl GR. (2006) Pooled association genome scanning for alcohol dependence using 104,268 SNPs: validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism. Am. J. Med. Genet. B Neuropsychiatr. Genet., 141B (8): 844-53. [PMID:16894614]

51. Johnson EN, Appelbaum ER, Carpenter DC, Cox RF, Disa J, Foley JJ, Ghosh SK, Naselsky DP, Pullen MA, Sarau HM et al.. (2004) Neuromedin U elicits cytokine release in murine Th2-type T cell clone D10.G4.1. J. Immunol., 173 (12): 7230-8. [PMID:15585845]

52. 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]

53. Jászberényi M, Bagosi Z, Thurzó B, Földesi I, Telegdy G. (2007) Endocrine and behavioral effects of neuromedin S. Horm Behav, 52 (5): 631-9. [PMID:17900576]

54. Kaczmarek P, Malendowicz LK, Fabis M, Ziolkowska A, Pruszynska-Oszmalek E, Sassek M, Wojciechowicz T, Szczepankiewicz D, Andralojc K, Szkudelski T et al.. (2009) Does somatostatin confer insulinostatic effects of neuromedin u in the rat pancreas?. Pancreas, 38 (2): 208-12. [PMID:18948835]

55. 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]

56. Kage R, O'Harte F, Thim L, Conlon JM. (1991) Rabbit neuromedin U-25: lack of conservation of a posttranslational processing site. Regul. Pept., 33 (2): 191-8. [PMID:1882085]

57. Kanematsu-Yamaki Y, Nishizawa N, Kaisho T, Nagai H, Mochida T, Asakawa T, Inooka H, Dote K, Fujita H, Matsumiya K et al.. (2017) Potent Body Weight-Lowering Effect of a Neuromedin U Receptor 2-selective PEGylated Peptide. J. Med. Chem., 60 (14): 6089-6097. [PMID:28657315]

58. Kasper JM, McCue DL, Milton AJ, Szwed A, Sampson CM, Huang M, Carlton S, Meltzer HY, Cunningham KA, Hommel JD. (2016) Gamma-Aminobutyric Acidergic Projections From the Dorsal Raphe to the Nucleus Accumbens Are Regulated by Neuromedin U. Biol. Psychiatry, 80 (11): 878-887. [PMID:27105831]

59. Kasper JM, Smith AE, Hommel JD. (2018) Cocaine-Evoked Locomotor Activity Negatively Correlates With the Expression of Neuromedin U Receptor 2 in the Nucleus Accumbens. Front Behav Neurosci, 12: 271. [PMID:30483076]

60. 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]

61. 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]

62. 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]

63. Lee WH, Liu SB, Shen JH, Jin Y, Lai R, Zhang Y. (2005) Identification and molecular cloning of a novel neuromedin U analog from the skin secretions of toad Bombina maxima. Regul. Pept., 129 (1-3): 43-7. [PMID:15927697]

64. Lin TY, Huang WL, Lee WY, Luo CW. (2015) Identifying a Neuromedin U Receptor 2 Splice Variant and Determining Its Roles in the Regulation of Signaling and Tumorigenesis In Vitro. PLoS ONE, 10 (8): e0136836. [PMID:26317338]

65. Lin TY, Wu FJ, Chang CL, Li Z, Luo CW. (2016) NMU signaling promotes endometrial cancer cell progression by modulating adhesion signaling. Oncotarget, 7 (9): 10228-42. [PMID:26849234]

66. Lydall GJ, Bass NJ, McQuillin A, Lawrence J, Anjorin A, Kandaswamy R, Pereira A, Guerrini I, Curtis D, Vine AE et al.. (2011) Confirmation of prior evidence of genetic susceptibility to alcoholism in a genome-wide association study of comorbid alcoholism and bipolar disorder. Psychiatr. Genet., 21 (6): 294-306. [PMID:21876473]

67. 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]

68. Malendowicz LK, Andreis PG, Markowska A, Nowak M, Warchol JB, Neri G, Nussdorfer GG. (1994) Effects of neuromedin U-8 on the secretory activity of the rat adrenal cortex: evidence for an indirect action requiring the presence of the zona medullaris. Res Exp Med (Berl), 194 (2): 69-79. [PMID:8059061]

69. Malendowicz LK, Nussdorfer GG, Nowak KW, Mazzocchi G. (1993) Effects of neuromedin U-8 on the rat pituitary-adrenocortical axis. In Vivo, 7 (5): 419-22. [PMID:8110984]

70. Mangold C, Ksiazek I, Yun SW, Berger E, Binkert C. (2008) Distribution of neuromedin U binding sites in the rat CNS revealed by in vitro receptor autoradiography. Neuropeptides, 42 (4): 377-86. [PMID:18547640]

71. 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.

72. Maruyama K, Konno N, Ishiguro K, Wakasugi T, Uchiyama M, Shioda S, Matsuda K. (2008) Isolation and characterisation of four cDNAs encoding neuromedin U (NMU) from the brain and gut of goldfish, and the inhibitory effect of a deduced NMU on food intake and locomotor activity. J. Neuroendocrinol., 20 (1): 71-8. [PMID:18081554]

73. Masuda Y, Kumano S, Noguchi J, Sakamoto K, Inooka H, Ohtaki T. (2017) PEGylated neuromedin U-8 shows long-lasting anorectic activity and anti-obesity effect in mice by peripheral administration. Peptides, 94: 99-105. [PMID:28400225]

74. McCue DL, Kasper JM, A, Hommel JD. (2019) Incubation of feeding behavior is regulated by neuromedin U receptor 2 in the paraventricular nucleus of the hypothalamus. Behav. Brain Res., 359: 763-770. [PMID:30227148]

75. 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]

76. 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]

77. Minamino N, Kangawa K, Honzawa M, Matsuo H. (1988) Isolation and structural determination of rat neuromedin U. Biochem. Biophys. Res. Commun., 156 (1): 355-60. [PMID:3178840]

78. 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]

79. 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]

80. Miyazato M, Mori K, Ida T, Kojima M, Murakami N, Kangawa K. (2008) Identification and functional analysis of a novel ligand for G protein-coupled receptor, Neuromedin S. Regul. Pept., 145 (1-3): 37-41. [PMID:17870195]

81. 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]

82. Mori K, Miyazato M. (2016) Chapter 13 Neuromedin U/S. In Handbook of Hormones Edited by Takei Y, Ando H, Tsutsui K (Academic Press) 94. DOI: 10.1016/C2013-0-15395-0 [ISBN:9780128010280]

83. 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]

84. Mori K, Miyazato M, Kangawa K. (2008) Neuromedin S: discovery and functions. Results Probl Cell Differ, 46: 201-12. [PMID:18214396]

85. 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]

86. 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]

87. 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]

88. Murphy R, Turner CA, Furness JB, Parker L, Giraud A. (1990) Isolation and microsequence analysis of a novel form of neuromedin U from guinea pig small intestine. Peptides, 11 (3): 613-7. [PMID:2381877]

89. Nakahara K, Akagi A, Shimizu S, Tateno S, Qattali AW, Mori K, Miyazato M, Kangawa K, Murakami N. (2016) Involvement of endogenous neuromedin U and neuromedin S in thermoregulation. Biochem. Biophys. Res. Commun., 470 (4): 930-5. [PMID:26826380]

90. 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]

91. Nakahara K, Katayama T, Maruyama K, Ida T, Mori K, Miyazato M, Kangawa K, Murakami N. (2010) Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats. J. Endocrinol., 207 (2): 185-93. [PMID:20732934]

92. 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]

93. Nandha KA, Benito-Orfila MA, Smith DM, Bloom SR. (1993) Characterization of the rat uterine neuromedin U receptor. Endocrinology, 133 (2): 482-6. [PMID:8393763]

94. 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]

95. O'Harte F, Bockman CS, Abel PW, Conlon JM. (1991) Isolation, structural characterization and pharmacological activity of dog neuromedin U. Peptides, 12 (1): 11-5. [PMID:2052487]

96. O'Harte F, Bockman CS, Zeng W, Abel PW, Harvey S, Conlon JM. (1991) Primary structure and pharmacological activity of a nonapeptide related to neuromedin U isolated from chicken intestine. Peptides, 12 (4): 809-12. [PMID:1788145]

97. 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]

98. Peier AM, Desai K, Hubert J, Du X, Yang L, Qian Y, Kosinski JR, Metzger JM, Pocai A, Nawrocki AR et al.. (2011) Effects of peripherally administered neuromedin U on energy and glucose homeostasis. Endocrinology, 152 (7): 2644-54. [PMID:21586559]

99. 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]

100. Qassam HS, Butcher AJ, Tobin AB, Willars GB. Ligand-dependent temporal patterns of signalling and receptor phosphorylation at NMU2. Accessed on 08/05/2019. Modified on 08/05/2019. pA2 online- E-journal of the British Pharmacological Society,

101. 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]

102. Rahman AA, Shahid IZ, Pilowsky PM. (2011) Intrathecal neuromedin U induces biphasic effects on sympathetic vasomotor tone, increases respiratory drive and attenuates sympathetic reflexes in rat. Br. J. Pharmacol., 164 (2b): 617-31. [PMID:21488865]

103. Rani S, Corcoran C, Shiels L, Germano S, Breslin S, Madden S, McDermott MS, Browne BC, O'Donovan N, Crown J et al.. (2014) Neuromedin U: a candidate biomarker and therapeutic target to predict and overcome resistance to HER-tyrosine kinase inhibitors. Cancer Res., 74 (14): 3821-33. [PMID:24876102]

104. Rao SM, Auger JL, Gaillard P, Weissleder R, Wada E, Torres R, Kojima M, Benoist C, Mathis D, Binstadt BA. (2012) The neuropeptide neuromedin U promotes autoantibody-mediated arthritis. Arthritis Res. Ther., 14 (1): R29. [PMID:22314006]

105. Rovati GE, Capra V, Neubig RR. (2007) The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state. Mol. Pharmacol., 71 (4): 959-64. [PMID:17192495]

106. 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]

107. Sakura N, Ohta S, Uchida Y, Kurosawa K, Okimura K, Hashimoto T. (1991) Structure-activity relationships of rat neuromedin U for smooth muscle contraction. Chem. Pharm. Bull., 39 (8): 2016-20. [PMID:1797423]

108. Salmon AL, Johnsen AH, Bienert M, McMurray G, Nandha KA, Bloom SR, Shaw C. (2000) Isolation, structural characterization, and bioactivity of a novel neuromedin U analog from the defensive skin secretion of the Australasian tree frog, Litoria caerulea. J. Biol. Chem., 275 (7): 4549-54. [PMID:10671478]

109. 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]

110. 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]

111. 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]

112. Sharman JL, Mpamhanga CP, Spedding M, Germain P, Staels B, Dacquet C, Laudet V, Harmar AJ, NC-IUPHAR. (2011) IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data. Nucleic Acids Res., 39 (Database issue): D534-8. [PMID:21087994]

113. Shetzline SE, Rallapalli R, Dowd KJ, Zou S, Nakata Y, Swider CR, Kalota A, Choi JK, Gewirtz AM. (2004) Neuromedin U: a Myb-regulated autocrine growth factor for human myeloid leukemias. Blood, 104 (6): 1833-40. [PMID:15187020]

114. Shousha S, Nakahara K, Miyazato M, Kangawa K, Murakami N. (2005) Endogenous neuromedin U has anorectic effects in the Japanese quail. Gen. Comp. Endocrinol., 140 (3): 156-63. [PMID:15639143]

115. Smith AE, Kasper JM, Ara 13, Anastasio NC, Hommel JD. (2019) Binge-Type Eating in Rats is Facilitated by Neuromedin U Receptor 2 in the Nucleus Accumbens and Ventral Tegmental Area. Nutrients, 11 (2). DOI: 10.3390/nu11020327 [PMID:30717427]

116. Strader CD, Fong TM, Tota MR, Underwood D, Dixon RA. (1994) Structure and function of G protein-coupled receptors. Annu. Rev. Biochem., 63: 101-32. [PMID:7979235]

117. Sumi S, Inoue K, Kogire M, Doi R, Takaori K, Suzuki T, Yajima H, Tobe T. (1987) Effect of synthetic neuromedin U-8 and U-25, novel peptides identified in porcine spinal cord, on splanchnic circulation in dogs. Life Sci., 41 (13): 1585-90. [PMID:3626773]

118. 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]

119. Takahashi K, Furukawa C, Takano A, Ishikawa N, Kato T, Hayama S, Suzuki C, Yasui W, Inai K, Sone S et al.. (2006) The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer. Cancer Res., 66 (19): 9408-19. [PMID:17018595]

120. Takayama K, Mori K, Sohma Y, Taketa K, Taguchi A, Yakushiji F, Minamino N, Miyazato M, Kangawa K, Hayashi Y. (2015) Discovery of potent hexapeptide agonists to human neuromedin u receptor 1 and identification of their serum metabolites. ACS Med Chem Lett, 6 (3): 302-7. [PMID:25815150]

121. 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]

122. Takayama K, Mori K, Tanaka A, Nomura E, Sohma Y, Mori M, Taguchi A, Taniguchi A, Sakane T, Yamamoto A et al.. (2017) Discovery of a Human Neuromedin U Receptor 1-Selective Hexapeptide Agonist with Enhanced Serum Stability. J. Med. Chem., 60 (12): 5228-5234. [PMID:28548497]

123. Takayama K, Taguchi A, Yakushiji F, Hayashi Y. (2016) Identification of a degrading enzyme in human serum that hydrolyzes a C-terminal core sequence of neuromedin U. Biopolymers, 106 (4): 440-5. [PMID:26567043]

124. Tan CP, McKee KK, Liu Q, Palyha OC, Feighner SD, Hreniuk DL, Smith RG, Howard AD. (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 (2): 223-9. [PMID:9782091]

125. Tanaka M, Telegdy G. (2014) Neurotransmissions of antidepressant-like effects of neuromedin U-23 in mice. Behav. Brain Res., 259: 196-9. [PMID:24239690]

126. Tanida M, Satomi J, Shen J, Nagai K. (2009) Autonomic and cardiovascular effects of central neuromedin U in rats. Physiol. Behav., 96 (2): 282-8. [PMID:18977236]

127. Telegdy G, Adamik A. (2013) Anxiolytic action of neuromedin-U and neurotransmitters involved in mice. Regul. Pept., 186: 137-40. [PMID:23892031]

128. Teranishi H, Hayashi M, Higa R, Mori K, Miyazawa T, Hino J, Amano Y, Tozawa R, Ida T, Hanada T et al.. (2018) Role of neuromedin U in accelerating of non-alcoholic steatohepatitis in mice. Peptides, 99: 134-141. [PMID:29017855]

129. 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]

130. 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]

131. Vallöf D, Ulenius L, Egecioglu E, Engel JA, Jerlhag E. (2017) Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol-induced reward in rodents. Addict Biol, 22 (3): 640-651. [PMID:26769653]

132. Vallöf D, Vestlund J, Engel JA, Jerlhag E. (2016) The Anorexigenic Peptide Neuromedin U (NMU) Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice. PLoS ONE, 11 (5): e0154477. [PMID:27139195]

133. 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]

134. Westfall TD, McCafferty GP, Pullen M, Gruver S, Sulpizio AC, Aiyar VN, Disa J, Contino LC, Mannan IJ, Hieble JP. (2002) Characterization of neuromedin U effects in canine smooth muscle. J. Pharmacol. Exp. Ther., 301 (3): 987-92. [PMID:12023529]

135. 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]

136. Wu Y, McRoberts K, Berr SS, Frierson HF, Conaway M, Theodorescu D. (2007) Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia. Oncogene, 26 (5): 765-73. [PMID:16878152]

137. Yamashita K, Upadhyay S, Osada M, Hoque MO, Xiao Y, Mori M, Sato F, Meltzer SJ, Sidransky D. (2002) Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma. Cancer Cell, 2 (6): 485-95. [PMID:12498717]

138. You S, Gao L. (2018) Identification of NMU as a potential gene conferring alectinib resistance in non-small cell lung cancer based on bioinformatics analyses. Gene, 678: 137-142. [PMID:30096454]

139. 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]

140. Zeng H, Gragerov A, Hohmann JG, Pavlova MN, Schimpf BA, Xu H, Wu LJ, Toyoda H, Zhao MG, Rohde AD et al.. (2006) Neuromedin U receptor 2-deficient mice display differential responses in sensory perception, stress, and feeding. Mol. Cell. Biol., 26 (24): 9352-63. [PMID:17030627]

141. Zheng X, Guo L, Wang D, Deng X. (2014) p-Synephrine: a novel agonist for neuromedin U2 receptor. Biol. Pharm. Bull., 37 (5): 764-70. [PMID:24598981]

How to cite this page

To cite this family introduction, please use the following:

Database page citation (select format):