title: Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3.
abstract: Neuromedins are a family of peptides best known for their contractile activity on smooth muscle preparations. The biological mechanism of action of neuromedin U remains unknown, despite the fact that the peptide was first isolated in 1985. Here we show that neuromedin U potently activates the orphan G protein-coupled receptor FM3, with subnanomolar potency, when FM3 is transiently expressed in human HEK-293 cells. Neuromedins B, C, K, and N are all inactive at this receptor. Quantitative reverse transcriptase-polymerase chain reaction analysis of neuromedin U expression in a range of human tissues showed that the peptide is highly expressed in the intestine, pituitary, and bone marrow, with lower levels of expression seen in stomach, adipose tissue, lymphocytes, spleen, and the cortex. Similar analysis of FM3 expression showed that the receptor is widely expressed in human tissue with highest levels seen in adipose tissue, intestine, spleen, and lymphocytes, suggesting that neuromedin U may have a wide range of presently undetermined physiological effects. The discovery that neuromedin U is an endogenous agonist for FM3 will significantly aid the study of the full physiological role of this peptide.
authors.affiliation: Departments of Vascular Biology and Gene Expression Sciences, New Frontiers Science Park, SmithKline Beecham Pharmaceuticals, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom. philip_szekeres-1@sbphrd.com
authors.forename: P G
authors.initials: PG
authors.lastname: Szekeres
authors.forename: A I
authors.initials: AI
authors.lastname: Muir
authors.forename: L D
authors.initials: LD
authors.lastname: Spinage
authors.forename: J E
authors.initials: JE
authors.lastname: Miller
authors.forename: S I
authors.initials: SI
authors.lastname: Butler
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: G I
authors.initials: GI
authors.lastname: Rennie
authors.forename: P R
authors.initials: PR
authors.lastname: Murdock
authors.forename: L R
authors.initials: LR
authors.lastname: Fitzgerald
authors.forename: H l
authors.initials: Hl
authors.lastname: Wu
authors.forename: L J
authors.initials: LJ
authors.lastname: McMillan
authors.forename: S
authors.initials: S
authors.lastname: Guerrera
authors.forename: L
authors.initials: L
authors.lastname: Vawter
authors.forename: N A
authors.initials: NA
authors.lastname: Elshourbagy
authors.forename: J L
authors.initials: JL
authors.lastname: Mooney
authors.forename: D J
authors.initials: DJ
authors.lastname: Bergsma
authors.forename: S
authors.initials: S
authors.lastname: Wilson
authors.forename: J K
authors.initials: JK
authors.lastname: Chambers
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008565:Membrane Proteins; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000235:genetics; D017981:Receptors, Neurotransmitter; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D007295:Inositol Phosphates; D008565:Membrane Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U; D019204:GTP-Binding Proteins; D002118:Calcium