Identification of a novel neuromedin U receptor subtype expressed in the central nervous system.
Neuromedin U is a neuropeptide prominently expressed in the upper gastrointestinal tract and central nervous system. Recently, GPR66/FM-3 (NmU-R1) was identified as a specific receptor for neuromedin U. A BLAST search of the GenBank(TM) genomic database using the NmU-R1 cDNA sequence revealed a human genomic fragment encoding a G protein-coupled receptor that we designated NmU-R2 based on its homology to NmU-R1. The full-length NmU-R2 cDNA was subsequently cloned, stably expressed in 293 cells, and shown to mobilize intracellular calcium in response to neuromedin U. This response was dose-dependent (EC(50) = 5 nm) and specific in that other neuromedins did not induce a calcium flux in receptor-transfected cells. Expression analysis of human NmU-R2 demonstrated its mRNA to be most highly expressed in central nervous system tissues. Based on these data, we conclude that NmU-R2 is a novel neuromedin U receptor subtype that is likely to mediate central nervous system-specific neuromedin U effects.
Shan
L
L
Human Genome Research and Cardiovascular/Central Nervous System Research, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Qiao
X
X
Crona
J H
JH
Behan
J
J
Wang
S
S
Laz
T
T
Bayne
M
M
Gustafson
E L
EL
Monsma
F J
FJ
Hedrick
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000096:biosynthesis / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution
D018076:DNA, Complementary; D008024:Ligands; D008565:Membrane Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; D002118:Calcium