Identification and functional characterization of a novel subtype of neuromedin U receptor.
Neuromedin U is a bioactive peptide isolated originally from the porcine spinal cord. We recently identified neuromedin U as the cognate ligand for the orphan G protein-coupled receptor FM-3. In this study, we isolated cDNA coding for a novel G protein-coupled receptor, TGR-1, which was highly homologous with FM-3. We found that neuromedin U specifically and clearly elevated the extracellular acidification rates, arachidonic acid metabolite release, and intracellular Ca(2+) mobilization in Chinese hamster ovary cells expressing TGR-1. Radiolabeled neuromedin U specifically bound with high affinity to membrane fractions prepared from these cells. These results show that TGR-1, like FM-3, is a specific and functional receptor for neuromedin U. We analyzed TGR-1 mRNA tissue distribution in rats using quantitative reverse transcription-polymerase chain reaction and found it to considerably differ from that of FM-3 mRNA. TGR-1 mRNA was primarily expressed in the uterus, suggesting that TGR-1 mediates the contractile activity of neuromedin U in this tissue. The identification of specific and functional receptor subtypes for neuromedin U will facilitate the study of their physiological roles and the search for their specific agonists and antagonists.
Hosoya
M
M
Pharmaceutical Discovery Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki 300-4293, Japan.
Moriya
T
T
Kawamata
Y
Y
Ohkubo
S
S
Fujii
R
R
Matsui
H
H
Shintani
Y
Y
Fukusumi
S
S
Habata
Y
Y
Hinuma
S
S
Onda
H
H
Nishimura
O
O
Fujino
M
M
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction
D008565:Membrane Proteins; D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U; D019204:GTP-Binding Proteins