title: Identification of receptors for neuromedin U and its role in feeding.
abstract: Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species. It is widely distributed in the gut and central nervous system. Peripheral activities of NMU include stimulation of smooth muscle, increase of blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. An NMU receptor has not been molecularly identified. Here we show that the previously described orphan G-protein-coupled receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting. Intracerebroventricular administration of NMU markedly suppresses food intake in rats. These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.
authors.affiliation: Department of Metabolic Disorders, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Howard
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: S S
authors.initials: SS
authors.lastname: Pong
authors.forename: T N
authors.initials: TN
authors.lastname: Mellin
authors.forename: A
authors.initials: A
authors.lastname: Strack
authors.forename: X M
authors.initials: XM
authors.lastname: Guan
authors.forename: Z
authors.initials: Z
authors.lastname: Zeng
authors.forename: D L
authors.initials: DL
authors.lastname: Williams
authors.forename: S D
authors.initials: SD
authors.lastname: Feighner
authors.forename: C N
authors.initials: CN
authors.lastname: Nunes
authors.forename: B
authors.initials: B
authors.lastname: Murphy
authors.forename: J N
authors.initials: JN
authors.lastname: Stair
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.forename: M K
authors.initials: MK
authors.lastname: Clements
authors.forename: C P
authors.initials: CP
authors.lastname: Tan
authors.forename: K K
authors.initials: KK
authors.lastname: McKee
authors.forename: D L
authors.initials: DL
authors.lastname: Hreniuk
authors.forename: T P
authors.initials: TP
authors.lastname: McDonald
authors.forename: K R
authors.initials: KR
authors.lastname: Lynch
authors.forename: J F
authors.initials: JF
authors.lastname: Evans
authors.forename: C P
authors.initials: CP
authors.lastname: Austin
authors.forename: C T
authors.initials: CT
authors.lastname: Caskey
authors.forename: L H
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D005215:Fasting; D005247:Feeding Behavior / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000502:physiology*; D016415:Sequence Alignment; D014018:Tissue Distribution
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U