Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3.
Neuromedin U is a bioactive peptide first isolated from porcine spinal cord. In this paper, we demonstrate that neuromedin U is the cognate ligand for the orphan G protein-coupled receptor, FM-3, isolated originally as a homologue of neurotensin and growth hormone secretogogue receptors. Neuromedin U induced specific and evident elevation of extracellular acidification rates, arachidonic acid metabolite release, and intracellular Ca(2+) mobilization in Chinese hamster ovary cells expressing human FM-3. In addition, radiolabeled neuromedin U specifically bound to membrane fractions prepared from these cells with high affinity. We subsequently analyzed the tissue distribution of neuromedin U and FM-3 mRNAs in rats using quantitative reverse transcription-polymerase chain reaction. Neuromedin U mRNA was highly expressed in the gastrointestinal tract, and the highest expression was detected in the pituitary gland. On the other hand, FM-3 mRNA was highly expressed in the small intestine and lung, suggesting that neuromedin U plays important roles in these tissues. The identification of a specific and functional receptor for neuromedin U will facilitate studies on their physiological roles and the search for receptor agonists and antagonists.
Fujii
R
R
Discovery Research Laboratories I, Pharmaceutical Discovery Research Division, Takeda Chemical Industries, Ltd., Tsukuba, Ibaraki 300-4293, Japan.
Hosoya
M
M
Fukusumi
S
S
Kawamata
Y
Y
Habata
Y
Y
Hinuma
S
S
Onda
H
H
Nishimura
O
O
Fujino
M
M
D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D006224:Cricetinae; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection
D008024:Ligands; D008565:Membrane Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; C082444:neuromedin U receptor; C056900:neuromedin U; D016718:Arachidonic Acid; D002118:Calcium