Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8.
The structurally related orphan G-protein-coupled receptors GPR7 and GPR8 are expressed in the central nervous system, and their ligands have not been identified. Here, we report the identification of the endogenous ligand for both of these receptors. We purified the peptide ligand from porcine hypothalamus using stable Chinese hamster ovary cell lines expressing human GPR8 and cloned the cDNA encoding its precursor protein. The cDNA encodes two forms of the peptide ligand with lengths of 23 and 30 amino acid residues as mature peptides. We designated the two ligands neuropeptide W-23 (NPW23) and neuropeptide W-30 (NPW30). The amino acid sequence of NPW23 is completely identical to that of the N-terminal 23 residues of NPW30. Synthetic NPW23 and NPW30 activated and bound to both GPR7 and GPR8 at similar effective doses. Intracerebroventricular administration of NPW23 in rats increased food intake and stimulated prolactin release. These findings indicate that neuropeptide W is the endogenous ligand for both GPR7 and GPR8 and acts as a mediator of the central control of feeding and the neuroendocrine system.
Shimomura
Yukio
Y
Discovery Research Laboratories I and Discovery Research Laboratories II, Pharmaceutical Research Division, Takeda Chemical Industries Limited, 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan. Shimomura_Yukio@takeda.co.jp
Harada
Mioko
M
Goto
Mika
M
Sugo
Tsukasa
T
Matsumoto
Yoshio
Y
Abe
Michiko
M
Watanabe
Takuya
T
Asami
Taiji
T
Kitada
Chieko
C
Mori
Masaaki
M
Onda
Haruo
H
Fujino
Masahiko
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015723:Gene Library; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification*; D010455:Peptides / Q000737:chemistry; D037342:Pertussis Toxin / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013552:Swine; D013997:Time Factors
D018076:DNA, Complementary; C467732:GRP8 protein, human; D008024:Ligands; C467731:NPW protein, human; D009479:Neuropeptides; D010455:Peptides; D018013:Receptors, Neuropeptide; D000242:Cyclic AMP; D037342:Pertussis Toxin