Identification of a novel neuromedin U receptor subtype expressed in the central nervous system

被引:99
作者
Shan, LX
Qiao, XD
Crona, JH
Behan, J
Wang, S
Laz, T
Bayne, M
Gustafson, EL
Monsma, FJ
Hedrick, JA
机构
[1] Schering Plough Res Inst, Human Genome Res, Kenilworth, NJ 07033 USA
[2] Schering Plough Res Inst, Cardiovasc Cent Nervous Syst Res, Kenilworth, NJ 07033 USA
关键词
D O I
10.1074/jbc.C000522200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (EC50 = 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.
引用
收藏
页码:39482 / 39486
页数:5
相关论文
共 32 条
[1]   CLONING AND CHARACTERIZATION OF THE CDNA-ENCODING THE HUMAN NEUROMEDIN U (NMU) PRECURSOR - NMU EXPRESSION IN THE HUMAN GASTROINTESTINAL-TRACT [J].
AUSTIN, C ;
LO, G ;
NANDHA, KA ;
MELEAGROS, L ;
BLOOM, SR .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 1995, 14 (02) :157-169
[2]   THE MOTOR EFFECT OF NEUROMEDIN-U ON RAT STOMACH INVITRO [J].
BENITOORFILA, MA ;
DOMIN, J ;
NANDHA, KA ;
BLOOM, SR .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 193 (03) :329-333
[3]   EVIDENCE THAT NEUROMEDIN-U MAY REGULATE GUT MOTILITY IN REPTILES BUT NOT IN MAMMALS [J].
BOCKMAN, CS ;
ABEL, PW ;
HICKS, JW ;
CONLON, JM .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 171 (2-3) :255-257
[4]   NEUROMEDIN-U OCTAPEPTIDE ALTERS ION-TRANSPORT IN PORCINE JEJUNUM [J].
BROWN, DR ;
QUITO, FL .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 155 (1-2) :159-162
[5]   PRIMARY STRUCTURE OF NEUROMEDIN-U FROM THE RAT [J].
CONLON, JM ;
DOMIN, J ;
THIM, L ;
DIMARZO, V ;
MORRIS, HR ;
BLOOM, SR .
JOURNAL OF NEUROCHEMISTRY, 1988, 51 (03) :988-991
[6]   Chimeric G proteins allow a high-throughput signaling assay of Gi-coupled receptors [J].
Coward, P ;
Chan, SDH ;
Wada, HG ;
Humphries, GM ;
Conklin, BR .
ANALYTICAL BIOCHEMISTRY, 1999, 270 (02) :242-248
[7]   THE PURIFICATION AND SEQUENCE-ANALYSIS OF AN AVIAN NEUROMEDIN-U [J].
DOMIN, J ;
BENITOORFILA, MA ;
NANDHA, KA ;
AITKEN, A ;
BLOOM, SR .
REGULATORY PEPTIDES, 1992, 41 (01) :1-8
[8]   Receptor for motilin identified in the human gastrointestinal system [J].
Feighner, SD ;
Tan, CP ;
McKee, KK ;
Palyha, OC ;
Hreniuk, DL ;
Pong, SS ;
Austin, CP ;
Figueroa, D ;
MacNeil, D ;
Cascieri, MA ;
Nargund, R ;
Bakshi, R ;
Abramovitz, M ;
Stocco, R ;
Kargman, S ;
O'Neill, G ;
Van der Ploeg, LHT ;
Evans, J ;
Patchett, AA ;
Smith, RG ;
Howard, AD .
SCIENCE, 1999, 284 (5423) :2184-2188
[9]   Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3 [J].
Fujii, R ;
Hosoya, M ;
Fukusumi, S ;
Kawamata, Y ;
Habata, Y ;
Hinuma, S ;
Onda, H ;
Nishimura, O ;
Fujino, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (28) :21068-21074
[10]   REGIONAL HEMODYNAMIC-EFFECTS OF NEUROMEDIN-U IN CONSCIOUS RATS [J].
GARDINER, SM ;
COMPTON, AM ;
BENNETT, T ;
DOMIN, J ;
BLOOM, SR .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (01) :R32-R38