Neuromedin U

Neuromedin U
Identifiers
SymbolNMU
NCBI gene10874
HGNC7859
OMIM605103
RefSeqNM_006681
UniProtP48645
Other data
LocusChr. 4 q12
Search for
StructuresSwiss-model
DomainsInterPro

Neuromedin U (NmU 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.[1][2][3][4][5][6][7][8]

Structure

Neuromedin U is a highly conserved neuropeptide present in many species, existing as multiple isoforms. 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 region of the entire peptide.[9] 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 amidated at the C-terminus, and all isoforms have identical C-terminal heptapeptides.

The sequence of neuromedin U-23 in rats is: YKVNEYQGPVAPSGGFFLFRPRN-(NH2).[1]

Function

The activation of NmU receptors leads to intracellular signal transduction via calcium mobilization, phosphoinositide (or PI) signaling, and the inhibition of cAMP production[10]

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.[11] 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 preganglionic neurons, thus controlling the activity.

Regulation

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.

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[11]

Role in disease

Cancer

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 proliferation, it induces c-Met, a proto-oncogene that encodes the mesenchymal-epithelial transition factor (MET) protein. Increased invasiveness as well as an increased hepatocyte growth factor (HGF)-mediated scattering suggest NmU is also involved in the HGF-c-Met paracrine loop regulating cell migration.[10]

Pain perception and stress response

The effect of NmU on stress and pain perception pathways has been demonstrated using mice. In contrast to NmU peptide-deficient mice, NmUR2 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 formalin test. Furthermore, facilitated excitatory synaptic transmission in spinal 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.

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 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 plasma levels of corticosterone, and stimulates the release of CRH from hypothalamic 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 antagonist (this is absent from CRH knockout mice).

Certain stress responses are abolished in NmU knockout mice. These results suggest that NmU significantly modulates nociceptive sensory transmission.[9]

See also

References

  1. ^ a b Brighton PJ, Szekeres PG, Willars GB (2004). "Neuromedin U and its receptors: structure, function, and physiological roles". Pharmacol. Rev. 56 (2): 231–48. doi:10.1124/pr.56.2.3. PMID 15169928. S2CID 884735.
  2. ^ 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 (August 2007). "Mice genetically deficient in neuromedin U receptor 2, but not neuromedin U receptor 1, have impaired nociceptive responses". Pain. 130 (3): 267–78. doi:10.1016/j.pain.2007.01.036. PMID 17379411. S2CID 23617159.
  3. ^ Novak CM, Zhang M, Levine JA (September 2007). "Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity". Brain Research. 1169: 57–68. doi:10.1016/j.brainres.2007.06.055. PMC 2735201. PMID 17706946.
  4. ^ Vigo E, Roa J, Pineda R, Castellano JM, Navarro VM, Aguilar E, Pinilla L, Tena-Sempere M (November 2007). "Novel role of the anorexigenic peptide neuromedin U in the control of LH secretion and its regulation by gonadal hormones and photoperiod". American Journal of Physiology. Endocrinology and Metabolism. 293 (5): E1265–73. doi:10.1152/ajpendo.00425.2007. PMID 17726140.
  5. ^ Iwai T, Iinuma Y, Kodani R, Oka J (May 2008). "Neuromedin U inhibits inflammation-mediated memory impairment and neuronal cell-death in rodents". Neuroscience Research. 61 (1): 113–9. doi:10.1016/j.neures.2008.01.018. PMID 18336945. S2CID 25260405.
  6. ^ Brighton PJ, Wise A, Dass NB, Willars GB (April 2008). "Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissue". The Journal of Pharmacology and Experimental Therapeutics. 325 (1): 154–64. doi:10.1124/jpet.107.132803. PMID 18180374. S2CID 33931881.
  7. ^ Tanida M, Satomi J, Shen J, Nagai K (February 2009). "Autonomic and cardiovascular effects of central neuromedin U in rats". Physiology & Behavior. 96 (2): 282–8. doi:10.1016/j.physbeh.2008.10.008. PMID 18977236. S2CID 38382442.
  8. ^ Mitchell JD, Maguire JJ, Kuc RE, Davenport AP (February 2009). "Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system". Cardiovascular Research. 81 (2): 353–61. doi:10.1093/cvr/cvn302. PMID 18987052.
  9. ^ a b 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 (December 2006). "Neuromedin U Receptor 2-Deficient Mice Display Differential Responses in Sensory Perception, Stress, and Feeding". Mol. Cell. Biol. 26 (24): 9352–63. doi:10.1128/MCB.01148-06. PMC 1698522. PMID 17030627.
  10. ^ a b Ketterer K, Kong B, Frank D, Giese NA, Bauer A, Hoheisel J, Korc M, Kleeff J, Michalski CW, Friess H (May 2009). "Neuromedin U is overexpressed in pancreatic cancer and increases invasiveness via the hepatocyte growth factor c-Met pathway". Cancer Letters. 277 (1): 72–81. doi:10.1016/j.canlet.2008.11.028. PMID 19118941.
  11. ^ a b Brighton PJ, Szekeres PG, Wise A, Willars GB (December 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". Molecular Pharmacology. 66 (6): 1544–56. doi:10.1124/mol.104.002337. PMID 15331768. S2CID 25349752.

Read other articles:

Teimei貞明Permaisuri Kaisar JepangPeriode30 Juli 1912 - 25 Desember 1926Penobatan10 November 1915Informasi pribadiKelahiranKujō Sadako(1884-06-25)25 Juni 1884Nishikichō, TokyoKematian17 Mei 1951(1951-05-17) (umur 66)Istana Ōmiya, TokyoPemakaman22 Juni 1951Pemakaman Kekaisaran Musashi, Hachiōji, TokyoWangsaWangsa KujōWangsa Yamato (pernikahan)AyahKujō MichitakaIbuNoma IkukoPasangan Yoshihito, Kaisar TaishoAnakHirohito, Kaisar JepangPangeran ChichibuPangeran TakamatsuPangeran Mikas...

 

GumengDesaKantor Desa GumengNegara IndonesiaProvinsiJawa TengahKabupatenKaranganyarKecamatanJenawiKode pos57794Kode Kemendagri33.13.17.2001 Luas... km²Jumlah penduduk... jiwaKepadatan... jiwa/km² Gumeng adalah desa di kecamatan Jenawi, Karanganyar, Jawa Tengah, Indonesia. Pembagian wilayah Desa Gumeng terdiri dari dusun/dukuh: Cetho Gumeng Kadipekso Milir Ngarjosari Pendidikan Lembaga pendidikan formal yang terletak di Desa Gumeng, antara lain: SD Negeri 01 Gumeng SD Negeri 03 Gumeng P...

 

Chinese TV series or program Another MePromotional posterAlso known asQiyue and AnshengWritten byYicong BaiJie LiDirected byLiang CuiStarringShen YueChen DulingXiong ZiqiZou TingweiCountry of originChinaOriginal languageMandarinNo. of episodes53ProductionProducerLuo JunhuiProduction locationNingboRunning time45 minutesOriginal releaseNetworkiQiyiReleaseJuly 22 (2019-07-22) –September 4, 2019 (2019-09-04) Another Me (Chinese: 七月与安生; pinyin: Qī Yuè Yǔ āns...

Strada statale 392del Lago del CoghinasLocalizzazioneStato Italia Regioni Sardegna DatiClassificazioneStrada statale InizioTempio Pausania FineOschiri Lunghezza32,432[1] km Provvedimento di istituzioneD.M. 1/02/1962 - G.U. 97 del 13/04/1962[2] GestoreANAS Manuale La 392 all'altezza di Tempio Pausania La strada statale 392 del Lago del Coghinas (SS 392) è una strada statale italiana di rilevanza regionale. È una trasversale che collega il centro Sardegna con Tempio....

 

Синелобый амазон Научная классификация Домен:ЭукариотыЦарство:ЖивотныеПодцарство:ЭуметазоиБез ранга:Двусторонне-симметричныеБез ранга:ВторичноротыеТип:ХордовыеПодтип:ПозвоночныеИнфратип:ЧелюстноротыеНадкласс:ЧетвероногиеКлада:АмниотыКлада:ЗавропсидыКласс:Пт�...

 

Indonesian vegetable soup This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Sayur bayam – news · newspapers · books · scholar · JSTOR (July 2020) (Learn how and when to remove this template message) Sayur bayamA bowl of sayur bayamAlternative namesSayur bening, sayur bayam beningCourseMain course (breakfast or...

B

  此條目介紹的是拉丁字母中的第2个字母。关于其他用法,请见「B (消歧义)」。   提示:此条目页的主题不是希腊字母Β、西里尔字母В、Б、Ъ、Ь或德语字母ẞ、ß。 BB b(见下)用法書寫系統拉丁字母英文字母ISO基本拉丁字母(英语:ISO basic Latin alphabet)类型全音素文字相关所属語言拉丁语读音方法 [b][p][ɓ](适应变体)Unicode编码U+0042, U+0062字母顺位2数值 2歷史發...

 

Questa voce o sezione sull'argomento biografie è priva o carente di note e riferimenti bibliografici puntuali. Sebbene vi siano una bibliografia e/o dei collegamenti esterni, manca la contestualizzazione delle fonti con note a piè di pagina o altri riferimenti precisi che indichino puntualmente la provenienza delle informazioni. Puoi migliorare questa voce citando le fonti più precisamente. Segui i suggerimenti del progetto di riferimento. Quatremère de Quincy, incisione di Françoi...

 

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Missouri Circuit Courts – news · newspapers · books · scholar · JSTOR (July 2012) (Learn how and when to remove this message) Jackson County courthouse for the 16th Circuit Court in Kansas City The Missouri Circuit Courts are the state trial courts of original ...

Untuk sutradara video daring, lihat Hu Ge (sutradara). Ini adalah nama Tionghoa; marganya adalah Hu. Hu GeHu Ge pada 2016Nama asal胡歌Lahir20 September 1982 (umur 41)ShanghaiKebangsaanTiongkokNama lainHughAlmamaterAkademi Drama Pusat Akademi Teater ShanghaiPekerjaan Pemeran Penyanyi Produser Tahun aktif2004–sekarangAgenHu Ge Studio (di bawah Tangren Media)Karier musikGenreMandopopInstrumenVokalLabelGold Typhoon Hu Ge Hanzi: 胡歌 Alih aksara Mandarin - Hanyu Pinyin: H...

 

حياة الإمبراطور الجديدةThe Emperor's New Groove (بالإنجليزية) معلومات عامةالتصنيف فيلم رسوم متحركة الصنف الفني  القائمة ... فيلم رفقاء — فيلم موسيقي[1][2] — فيلم استرجاع — فيلم رسوم متحركة تحريكًا تقليديًّا — فيلم كوميدي المواضيع empire (en) — نرجسية — السلوك العدواني عند الطف�...

 

Artikel ini membutuhkan rujukan tambahan agar kualitasnya dapat dipastikan. Mohon bantu kami mengembangkan artikel ini dengan cara menambahkan rujukan ke sumber tepercaya. Pernyataan tak bersumber bisa saja dipertentangkan dan dihapus.Cari sumber: Panjat tebing – berita · surat kabar · buku · cendekiawan · JSTOR (Maret 2014) Beberapa atau seluruh referensi dari artikel ini mungkin tidak dapat dipercaya kebenarannya. Bantulah dengan memberikan referensi...

Portable data center built into a 20-foot shipping container A Sun Modular Datacenter on display at the Sun Microsystems Executive Briefing Center in Menlo Park, California Sun Modular Datacenter (Sun MD, known in the prototype phase as Project Blackbox) is a portable data center built into a standard 20-foot intermodal container (shipping container) manufactured and marketed by Sun Microsystems (acquired in 2010 by Oracle Corporation). An external chiller and power were required for the oper...

 

Island town in Erie County, New York Town in New York, United StatesGrand Island La Grand Île (French)TownTown of Grand IslandSouth Grand Island BridgeNickname(s): La Grande ÎleMotto(s): A Grand Place to LiveLocation in Erie County and New York.Location of New York in the United StatesCoordinates: 43°00′43″N 78°57′33″W / 43.01194°N 78.95917°W / 43.01194; -78.95917Country United StatesState New YorkCountyErieIncorporated1852Government •...

 

American video streaming service This article is about the streaming service. For the media player hardware, see Apple TV. For the media player app from Apple, see Apple TV app. Apple TV+Logo used since 2019DeveloperApple Inc.Key people Tim Cook (Apple CEO)[1] Eddy Cue (Senior VP of Internet Software & Services)[1] Zack Van Amburg (Head of Worldwide Video Programming)[2] Jamie Erlicht (Head of Worldwide Video Programming)[2] Matt Cherniss (Head of Domestic ...

Annual golf tournament in the United States Golf tournament U.S. AmateurJerry Pate with U.S. Amateur trophy, 1974Tournament informationLocationParamus, New Jersey (2022)Established1895Course(s)Cherry Hills Country Club (2023)Par71 (2023)Length7,403 yd (6,769 m) (2022)Organized byUSGAFormatStroke play and match playMonth playedAugustCurrent champion Nick Dunlap The United States Amateur Championship, commonly known as the U.S. Amateur, is the leading annual golf tournament in the Uni...

 

American college basketball season 2015–16 Holy Cross Crusaders men's basketballPatriot League tournament championsNCAA tournament, First RoundConferencePatriot LeagueRecord15–20 (5–13 Patriot)Head coachBill Carmody (1st season)Assistant coaches Kevin Driscoll Joe Kennedy Freddie Owens Home arenaHart CenterSeasons← 2014–152016–17 → 2015–16 Patriot League men's basketball standings vte Conf Overall Team W   L   PCT W   L   PCT Buc...

 

Pour les articles homonymes, voir Haug. Thorleif Haug Thorleif Haug en 1924. Contexte général Sport Combiné nordique, ski de fond et saut à ski Biographie Nom dans la langue maternelle Thorleif Haug Nationalité sportive Norvégien Nationalité Norvège Naissance 28 septembre 1894 Lieu de naissance Lier Décès 12 décembre 1934 (à 40 ans) Lieu de décès Drammen Club Lier SkiløberforeningDrammen Ski ClubDrafn Palmarès Médailles obtenues Compétition Or Arg. Bro. Jeux olympiques...

Long-ranged guns for land warfare Artilleryman redirects here. For the racehorse, see Artilleryman (horse). For other uses, see Artillery (disambiguation). This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Artillery – news · newspapers · books · scholar · JSTOR (June 2022) (Learn how and when to remove this me...

 

Second largest city in Scania, Sweden For other uses, see Helsingborg (disambiguation). Place in Scania, SwedenHelsingborgTop: Sofiero Palace, Second left: Kärnan, Second right: Rådhuset (Helsingborg City Hall), Third left: Dunker Culture House, Third right: Ramlösa mineral water source site, Bottom: A cruise terminal in Helsingborg Bredgatan Port Coat of armsNickname: Pearl of the straitHelsingborgShow map of SkåneHelsingborgShow map of SwedenCoordinates: 56°03′N 12°43′E࿯...