https://www.wikidoc.org/api.php?action=feedcontributions&user=79.213.187.82&feedformat=atomwikidoc - User contributions [en]2024-03-28T10:44:06ZUser contributionsMediaWiki 1.40.0https://www.wikidoc.org/index.php?title=Neuromedin_U&diff=1413589Neuromedin U2016-10-01T12:43:54Z<p>79.213.187.82: /* Structure */</p>
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<div>{{infobox protein<br />
| Name = Neuromedin U<br />
| caption = <br />
| image = <br />
| width = <br />
| HGNCid = 7859<br />
| Symbol = NMU<br />
| AltSymbols = <br />
| EntrezGene = 10874<br />
| OMIM = 605103<br />
| RefSeq = NM_006681<br />
| UniProt = P48645<br />
| PDB = <br />
| ECnumber = <br />
| Chromosome = 4<br />
| Arm = q<br />
| Band = 12<br />
| LocusSupplementaryData = <br />
}}<br />
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'''Neuromedin U''' (or NmU) is a [[neuropeptide]] found in the brain of humans and other mammals, which has a number of diverse functions including contraction of smooth muscle, regulation of [[blood pressure]], pain perception, appetite, bone growth, and [[hormone]] release. It was first isolated from the [[spinal cord]] in 1985, and named after its ability to cause smooth [[muscle contraction]] in the uterus.<ref name="pmid15169928">{{cite journal |vauthors=Brighton PJ, Szekeres PG, Willars GB | title = Neuromedin U and its receptors: structure, function, and physiological roles | journal = Pharmacol. Rev. | volume = 56 | issue = 2 | pages = 231–48 | year = 2004 | pmid = 15169928 | doi = 10.1124/pr.56.2.3 }}</ref><ref name="pmid17379411">{{cite journal |vauthors=Torres R, Croll SD, Vercollone J, Reinhardt J, Griffiths J, Zabski S, Anderson KD, Adams NC, Gowen L, Sleeman MW, Valenzuela DM, Wiegand SJ, Yancopoulos GD, Murphy AJ |title=Mice genetically deficient in neuromedin U receptor 2, but not neuromedin U receptor 1, have impaired nociceptive responses |journal=Pain |volume=130 |issue=3 |pages=267–78 |date=August 2007 |pmid=17379411 |doi=10.1016/j.pain.2007.01.036 |url=}}</ref><ref name="pmid17706946">{{cite journal |vauthors=Novak CM, Zhang M, Levine JA |title=Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity |journal=Brain Research |volume=1169 |issue= |pages=57–68 |date=September 2007 |pmid=17706946 |doi=10.1016/j.brainres.2007.06.055 |url= |pmc=2735201}}</ref><ref name="pmid17726140">{{cite journal |vauthors=Vigo E, Roa J, Pineda R, Castellano JM, Navarro VM, Aguilar E, Pinilla L, Tena-Sempere M |title=Novel role of the anorexigenic peptide neuromedin U in the control of LH secretion and its regulation by gonadal hormones and photoperiod |journal=American Journal of Physiology. Endocrinology and Metabolism |volume=293 |issue=5 |pages=E1265–73 |date=November 2007 |pmid=17726140 |doi=10.1152/ajpendo.00425.2007 |url=}}</ref><ref name="pmid18336945">{{cite journal |vauthors=Iwai T, Iinuma Y, Kodani R, Oka J |title=Neuromedin U inhibits inflammation-mediated memory impairment and neuronal cell-death in rodents |journal=Neuroscience Research |volume=61 |issue=1 |pages=113–9 |date=May 2008 |pmid=18336945 |doi=10.1016/j.neures.2008.01.018 |url=}}</ref><ref name="pmid18180374">{{cite journal |vauthors=Brighton PJ, Wise A, Dass NB, Willars GB |title=Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissue |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=325 |issue=1 |pages=154–64 |date=April 2008 |pmid=18180374 |doi=10.1124/jpet.107.132803 |url=}}</ref><ref name="pmid18977236">{{cite journal |vauthors=Tanida M, Satomi J, Shen J, Nagai K |title=Autonomic and cardiovascular effects of central neuromedin U in rats |journal=Physiology & Behavior |volume=96 |issue=2 |pages=282–8 |date=February 2009 |pmid=18977236 |doi=10.1016/j.physbeh.2008.10.008 |url=}}</ref><ref name="pmid18987052">{{cite journal |vauthors=Mitchell JD, Maguire JJ, Kuc RE, Davenport AP |title=Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system |journal=Cardiovascular Research |volume=81 |issue=2 |pages=353–61 |date=February 2009 |pmid=18987052 |doi=10.1093/cvr/cvn302 |url=}}</ref><br />
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==Structure==<br />
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Neuromedin U is a highly conserved neuropeptide present in many species, existing as multiple [[isoform]]s. For example, in humans it is a 25 [[amino acid]] [[peptide]] (U-25) in rats it is 23-aas long (U-23) and it has been found to be as low as 8-aas long in some mammals. NMU-8 is identical to the [[C terminus]] of NMU-25, thus is the most highly [[conserved sequence|conserved]] region of the entire peptide.<ref name="pmid17030627">{{cite journal |vauthors=Zeng H, Gragerov A, Hohmann JG, Pavlova MN, Schimpf BA, Xu H, Wu LJ, Toyoda H, Zhao MG, Rohde AD, Gragerova G, Onrust R, Bergmann JE, Zhuo M, Gaitanaris GA | title = Neuromedin U Receptor 2-Deficient Mice Display Differential Responses in Sensory Perception, Stress, and Feeding | journal = Mol. Cell. Biol. | volume = 26 | issue = 24 | pages = 9352–63 |date=December 2006 | pmid = 17030627 | pmc = 1698522 | doi = 10.1128/MCB.01148-06 | url = }}</ref> The relative contribution of the different isoforms to the biological function of neuromedin U is generally not well understood. Neuromedin U, like many neuroactive peptides, is [[amidation|amidated]] at the C-terminus, and all isoforms have identical C-terminal heptapeptides.<br />
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The sequence of neuromedin U-23 in rats is: YKVNEYQGPVAPSGGFFLFRPRN-(NH2).<ref name="pmid15169928"/><br />
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==Function==<br />
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The activation of NmU receptors leads to intracellular [[signal transduction]] via calcium mobilization, [[phosphoinositide]] (or PI) signaling, and the inhibition of [[Cyclic adenosine monophosphate|cAMP]] production<ref name="pmid19118941">{{cite journal |vauthors=Ketterer K, Kong B, Frank D, Giese NA, Bauer A, Hoheisel J, Korc M, Kleeff J, Michalski CW, Friess H |title=Neuromedin U is overexpressed in pancreatic cancer and increases invasiveness via the hepatocyte growth factor c-Met pathway |journal=Cancer Letters |volume=277 |issue=1 |pages=72–81 |date=May 2009 |pmid=19118941 |doi=10.1016/j.canlet.2008.11.028 |url=}}</ref><br />
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NmU will contract smooth muscle only in a tissue- and species-specific manner. Intracerebroventricular (or i.c.v) administration of the neuropeptide mediates stress response and increases both the arterial pressure and heart rate.<ref name="pmid15331768">{{cite journal |vauthors=Brighton PJ, Szekeres PG, Wise A, Willars GB |title=Signaling and ligand binding by recombinant neuromedin U receptors: evidence for dual coupling to Galphaq/11 and Galphai and an irreversible ligand-receptor interaction |journal=Molecular Pharmacology |volume=66 |issue=6 |pages=1544–56 |date=December 2004 |pmid=15331768 |doi=10.1124/mol.104.002337 |url=}}</ref> i.c.v administration of NmU elevates the plasma adrenaline levels, though has no effect on the amount of plasma noradrenaline. It has been suggested that large doses () of NmU inhibits the activity of the [[paraventricular nucleus of hypothalamus]] and/or the [[sympathetic nervous system|sympathetic]] [[preganglionic neurons]], thus controlling the activity.<br />
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==Regulation==<br />
Neuromedin U is mediated by two receptors, peripheral NmUR1 and central nervous system NmUR2. Both receptors are examples of Class A G-protein coupled receptors (or GPCRs) with a distinct distributional pattern. NmUR1 is expressed predominantly in the peripheral nervous system, with highest levels in the gastrointestinal tract, whereas NmUR2 is mostly found in the central nervous system, with greatest expression in the hypothalamus, medulla, and spinal cord.<br />
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The discovery of set distribution patterns has begun to allow assignation of specific roles of the two receptor subtypes within the body. What is known for certain is that recombinant NmU receptors will increase the internal calcium concentration, signaling via the [[MAPK/ERK pathway]]<ref name="pmid15331768"/><br />
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== Role in disease ==<br />
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=== Cancer===<br />
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Its role in cancer is not yet fully understood, though NmU and its receptor NMUR2 have been shown to be over-expressed in human pancreatic cancers compared to normal cells. Studies also showed NmU serum levels decreased after the tumors were removed, as NmU and its receptor are localized predominantly in cancer cells. Although NmU exerts no effect on cancer cell [[Cell growth|proliferation]], it induces c-Met, a [[proto-oncogene]] that encodes the [[Mesenchymal stem cell|mesenchymal]]-[[Epithelium|epithelial]] transition factor (MET) protein. Increased [[invasive cancer|invasiveness]] as well as an increased hepatocyte growth factor ([[Hepatocyte growth factor|HGF]])-mediated scattering suggest NmU is also involved in the HGF-c-Met [[Paracrine signalling|paracrine]] loop regulating [[cell migration]].<ref name="pmid19118941" /><br />
<!-- === Obesity === --><br />
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=== Pain perception and stress response ===<br />
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The effect of NmU on stress and pain perception pathways has been demonstrated using mice. In contrast to NmU peptide-deficient mice, NmUR2 [[Gene knockout|knockout]] (KO) mice appeared normal with regard to stress, anxiety, body weight regulation, and food consumption. However, the NmUR2 KO mice exhibit reduced pain sensitivity in both hot plate test and the chronic phase of the [[Formaldehyde|formalin]] test. Furthermore, facilitated excitatory [[Neurotransmission|synaptic transmission]] in spinal [[Posterior horn of spinal cord|dorsal horn]] [[neurons]], a mechanism by which NmU stimulates pain, did not occur in NmUR2 KO mice. Both NmUR2 expression and NmU-23 binding sites are highly localized to the outer layers of the spinal dorsal horn, and administration of NmU via intracerebroventricular (ICV) injections usually increases pain sensitivity in rats and mice.<br />
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The expression of NmUR2 in the [[paraventricular nucleus of hypothalamus]] (PVN), a major site for the release of [[Corticotropin-releasing hormone]] (CRH), suggests an alternative role in mediating stress response. NmU and its receptors are also abundantly expressed in [[Nociception|nociceptive]] sensory pathways, including the [[dorsal root ganglia]] (DRG), [[spinal cord]], and [[brainstem]]. In particular, NmU induces [[hyperalgesia]], [[allodynia]], and increased persistent pain after formalin injection. ICV injections of NmU in rats and mice induce behavior responses associated with activation of the nociceptive pathways, for example it will increase [[Blood plasma|plasma]] levels of [[corticosterone]], and stimulates the release of CRH from hypothalamic [[Explant culture|explants]] ''[[in vitro]]''. Central administration of NmU also induces expression of key [[genes]] in hypothalamic areas associated with stress, as well as stress-related behaviours that can be blocked by CRH [[Receptor antagonist|antagonist]] (this is absent from CRH knockout mice).<br />
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Certain stress responses are abolished in NmU knockout mice. These results suggest that NmU significantly modulates nociceptive sensory transmission.<ref name="pmid17030627" /><br />
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==See also==<br />
* [[Neuromedin U receptor]]<br />
* [[Neuromedin S]]<br />
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==References==<br />
{{reflist}}<br />
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==External links==<br />
* {{MeshName|neuromedin+U}}<br />
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{{Neuropeptides}}<br />
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[[Category:Neuropeptides]]</div>79.213.187.82