270:. 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.
350:, 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.
242:
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. i.c.v administration of NmU elevates the plasma adrenaline levels,
493:
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
290:
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
273:
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
586:
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".
847:
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".
886:
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".
335:(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
385:, 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
211:
region of the entire peptide. 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
795:
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).
1419:
37:
1339:
413:
Certain stress responses are abolished in NmU knockout mice. These results suggest that NmU significantly modulates nociceptive sensory transmission.
965:
622:
Iwai T, Iinuma Y, Kodani R, Oka J (May 2008). "Neuromedin U inhibits inflammation-mediated memory impairment and neuronal cell-death in rodents".
354:
244:
665:
Brighton PJ, Wise A, Dass NB, Willars GB (April 2008). "Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissue".
168:
found in the brain of humans and other mammals, which has a number of diverse functions including contraction of smooth muscle, regulation of
331:
The effect of NmU on stress and pain perception pathways has been demonstrated using mice. In contrast to NmU peptide-deficient mice, NmUR2
1454:
243:
though has no effect on the amount of plasma noradrenaline. It has been suggested that large doses () of NmU inhibits the activity of the
61:
203:(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
49:
1329:
358:
42:
708:
Tanida M, Satomi J, Shen J, Nagai K (February 2009). "Autonomic and cardiovascular effects of central neuromedin U in rats".
450:
Brighton PJ, Szekeres PG, Willars GB (2004). "Neuromedin U and its receptors: structure, function, and physiological roles".
236:
753:"Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system"
344:
361:(CRH), suggests an alternative role in mediating stress response. NmU and its receptors are also abundantly expressed in
1344:
539:"Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity"
958:
248:
797:"Neuromedin U Receptor 2-Deficient Mice Display Differential Responses in Sensory Perception, Stress, and Feeding"
1364:
937:
312:
406:
in hypothalamic areas associated with stress, as well as stress-related behaviours that can be blocked by CRH
267:
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Neuromedin U is a highly conserved neuropeptide present in many species, existing as multiple
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85:
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at the C-terminus, and all isoforms have identical C-terminal heptapeptides.
1349:
1334:
1180:
1170:
1153:
1010:
678:
382:
374:
291:
predominantly in cancer cells. Although NmU exerts no effect on cancer cell
213:
908:
900:
869:
830:
778:
729:
686:
643:
608:
572:
515:
471:
219:
The sequence of neuromedin U-23 in rats is: YKVNEYQGPVAPSGGFFLFRPRN-(NH2).
943:
1324:
1303:
1298:
1242:
812:
769:
752:
398:
90:
1369:
1354:
974:
347:
200:
193:
173:
463:
1290:
73:
315:)-mediated scattering suggest NmU is also involved in the HGF-c-Met
1203:
403:
66:
947:
751:
Mitchell JD, Maguire JJ, Kuc RE, Davenport AP (February 2009).
402:. Central administration of NmU also induces expression of key
1429:
589:
American
Journal of Physiology. Endocrinology and Metabolism
667:
The
Journal of Pharmacology and Experimental Therapeutics
227:
The activation of NmU receptors leads to intracellular
393:, and stimulates the release of CRH from hypothalamic
262:
Neuromedin U is mediated by two receptors, peripheral
180:
in 1985, and named after its ability to cause smooth
1312:
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28:
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18:
311:as well as an increased hepatocyte growth factor (
881:
879:
842:
840:
537:Novak CM, Zhang M, Levine JA (September 2007).
1420:Pituitary adenylate cyclase-activating peptide
790:
788:
445:
443:
172:, pain perception, appetite, bone growth, and
1340:Cocaine- and amphetamine-regulated transcript
959:
8:
307:transition factor (MET) protein. Increased
1199:
1006:
966:
952:
944:
339:test. Furthermore, facilitated excitatory
119:
936:at the U.S. National Library of Medicine
820:
768:
562:
410:(this is absent from CRH knockout mice).
235:(or PI) signaling, and the inhibition of
176:release. It was first isolated from the
439:
357:(PVN), a major site for the release of
355:paraventricular nucleus of hypothalamus
245:paraventricular nucleus of hypothalamus
15:
7:
196:. For example, in humans it is a 25
327:Pain perception and stress response
207:of NMU-25, thus is the most highly
14:
254:, thus controlling the activity.
365:sensory pathways, including the
1330:Calcitonin gene-related peptide
359:Corticotropin-releasing hormone
353:The expression of NmUR2 in the
555:10.1016/j.brainres.2007.06.055
1:
722:10.1016/j.physbeh.2008.10.008
377:. In particular, NmU induces
1345:Delta-sleep-inducing peptide
862:10.1016/j.canlet.2008.11.028
636:10.1016/j.neures.2008.01.018
1455:Genes on human chromosome 4
266:and central nervous system
1476:
601:10.1152/ajpendo.00425.2007
508:10.1016/j.pain.2007.01.036
231:via calcium mobilization,
1365:Gastrin-releasing peptide
710:Physiology & Behavior
118:
938:Medical Subject Headings
757:Cardiovascular Research
679:10.1124/jpet.107.132803
1415:Pancreatic polypeptide
901:10.1124/mol.104.002337
889:Molecular Pharmacology
295:, it induces c-Met, a
624:Neuroscience Research
423:Neuromedin U receptor
341:synaptic transmission
252:preganglionic neurons
1360:Galanin-like peptide
813:10.1128/MCB.01148-06
367:dorsal root ganglia
229:signal transduction
770:10.1093/cvr/cvn302
182:muscle contraction
1442:
1441:
1438:
1437:
1189:
1188:
464:10.1124/pr.56.2.3
299:that encodes the
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319:loop regulating
276:MAPK/ERK pathway
233:phosphoinositide
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1390:Neuropeptide VF
1385:Neuropeptide SF
1380:Neuropeptide FF
1375:Neuropeptide AF
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1002:Opioid peptides
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807:(24): 9352ā63.
801:Mol. Cell. Biol
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281:Role in disease
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184:in the uterus.
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1400:Neuropeptide Y
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1395:Neuropeptide S
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1128:Leu-enkephalin
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1123:Met-enkephalin
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1054:Ī²-Neoendorphin
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1049:Ī±-Neoendorphin
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928:External links
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895:(6): 1544ā56.
875:
850:Cancer Letters
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543:Brain Research
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452:Pharmacol. Rev
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391:corticosterone
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321:cell migration
297:proto-oncogene
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1077:Endomorphin-2
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1072:Endomorphin-1
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1405:Neurophysins
1280:
1233:Neurokinin B
1228:Neurokinin A
1064:Endomorphins
990:
934:neuromedin+U
892:
888:
856:(1): 72ā81.
853:
849:
804:
800:
760:
756:
746:
716:(2): 282ā8.
713:
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627:
623:
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592:
588:
581:
546:
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499:
495:
494:responses".
488:
455:
451:
428:Neuromedin S
412:
397:
379:hyperalgesia
352:
330:
309:invasiveness
289:
272:
261:
241:
226:
218:
191:
166:neuropeptide
161:
157:
154:Neuromedin U
153:
152:
110:
19:Neuromedin U
1410:Neurotensin
1320:Angiotensin
1259:Neuromedins
1248:Physalaemin
1223:Substance P
1217:Tachykinins
1212:Bradykinins
1159:Hemorphin-4
1144:Adrenorphin
1115:Enkephalins
1105:Ī³-Endorphin
1100:Ī²-Endorphin
1095:Ī±-Endorphin
1034:Dynorphin B
1024:Dynorphin A
1019:Dynorphin A
371:spinal cord
363:nociceptive
345:dorsal horn
301:mesenchymal
249:sympathetic
247:and/or the
239:production
178:spinal cord
132:Swiss-model
24:Identifiers
1449:Categories
1239:amphibian
1176:Spinorphin
1166:Nociceptin
1149:Amidorphin
1087:Endorphins
1044:Leumorphin
1011:Dynorphins
434:References
408:antagonist
389:levels of
343:in spinal
305:epithelial
258:Regulation
205:C terminus
198:amino acid
128:Structures
123:Search for
97:Other data
1350:FMRFamide
1335:Carnosine
1219:: mammal
1181:Valorphin
1171:Opiorphin
1154:Hemorphin
549:: 57ā68.
383:allodynia
375:brainstem
317:paracrine
209:conserved
188:Structure
79:NM_006681
38:NCBI gene
1325:Bombesin
1243:Kassinin
993:hormones
986:Hormones
975:Peptides
917:25349752
909:15331768
870:19118941
831:17030627
779:18987052
738:38382442
730:18977236
695:33931881
687:18180374
652:25260405
644:18336945
609:17726140
573:17706946
524:23617159
516:17379411
472:15169928
417:See also
399:in vitro
395:explants
337:formalin
333:knockout
223:Function
214:amidated
194:isoforms
142:InterPro
1425:RVD-HpĪ±
1370:Ghrelin
1355:Galanin
1291:Orexins
822:1698522
564:2735201
369:(DRG),
348:neurons
201:peptide
174:hormone
164:) is a
138:Domains
86:UniProt
1204:Kinins
1137:Others
940:(MeSH)
915:
907:
868:
829:
819:
777:
736:
728:
693:
685:
650:
642:
607:
571:
561:
522:
514:
480:884735
478:
470:
387:plasma
373:, and
286:Cancer
108:Chr. 4
91:P48645
74:RefSeq
67:605103
29:Symbol
1313:Other
1194:Other
913:S2CID
734:S2CID
691:S2CID
648:S2CID
520:S2CID
476:S2CID
404:genes
268:NmUR2
264:NmUR1
103:Locus
43:10874
991:see
905:PMID
866:PMID
827:PMID
775:PMID
726:PMID
683:PMID
640:PMID
605:PMID
569:PMID
547:1169
512:PMID
496:Pain
468:PMID
237:cAMP
62:OMIM
55:7859
50:HGNC
1430:VGF
1026:1ā8
897:doi
858:doi
854:277
817:PMC
809:doi
765:doi
718:doi
675:doi
671:325
632:doi
597:doi
593:293
559:PMC
551:doi
504:doi
500:130
460:doi
313:HGF
162:NMU
160:or
158:NmU
112:q12
32:NMU
1451::
977::
911:.
903:.
893:66
891:.
878:^
864:.
852:.
839:^
825:.
815:.
805:26
803:.
799:.
787:^
773:.
761:81
759:.
755:.
732:.
724:.
714:96
712:.
689:.
681:.
669:.
646:.
638:.
628:61
626:.
603:.
591:.
567:.
557:.
545:.
541:.
518:.
510:.
498:.
474:.
466:.
456:56
454:.
442:^
381:,
323:.
1304:B
1299:A
1281:U
1276:S
1271:N
1266:B
967:e
960:t
953:v
919:.
899::
872:.
860::
833:.
811::
781:.
767::
740:.
720::
697:.
677::
654:.
634::
611:.
599::
575:.
553::
526:.
506::
482:.
462::
303:-
156:(
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