Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3).
GPR66 is an orphan G-protein-coupled receptor (GPCR) whose structure is similar to the ghrelin and motilin receptors. We have tried to purify a natural ligand for GPR66 in rat tissues and identified a 23-amino-acid peptide as the endogenous ligand. Sequence analysis revealed the peptide as neuromedin U (NMU), a smooth-muscle-contracting peptide that was first purified from porcine spinal cord by our group. NMU binds to GPR66-expressing cells with high specificity to induce intracellular calcium mobilization. When NMU was injected intracerebroventricularly (ICV) into rats, it potently suppressed food intake. In contrast, ICV injection of NMU-antibody increased food intake. These results suggest that NMU is a potent endogenous anorexic peptide.
Kojima
M
M
Department of Biochemistry, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka, 565-8565, Japan. mkoijima@ri.ncvc.go.jp
Haruno
R
R
Nakazato
M
M
Date
Y
Y
Murakami
N
N
Hanada
R
R
Matsuo
H
H
Kangawa
K
K
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D008024:Ligands; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017981:Receptors, Neurotransmitter; D020539:Sequence Analysis, Protein
D008024:Ligands; D008565:Membrane Proteins; D009479:Neuropeptides; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U