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Proc Natl Acad Sci U S A
2003 May 13;10010:6251-6. doi: 10.1073/pnas.0837789100.
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Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8.
Tanaka H
,
Yoshida T
,
Miyamoto N
,
Motoike T
,
Kurosu H
,
Shibata K
,
Yamanaka A
,
Williams SC
,
Richardson JA
,
Tsujino N
,
Garry MG
,
Lerner MR
,
King DS
,
O'Dowd BF
,
Sakurai T
,
Yanagisawa M
.
???displayArticle.abstract??? GPR7 and GPR8 are orphan G protein-coupled receptors that are highly similar to each other. These receptors are expressed predominantly in brain, suggesting roles in central nervous system function. We have purified an endogenous peptide ligand for GPR7 from bovine hypothalamus extracts. This peptide, termed neuropeptide B (NPB), has a C-6-brominated tryptophan residue at the N terminus. It binds and activates human GPR7 or GPR8 with median effective concentrations (EC(50)) of 0.23 nM and 15.8 nM, respectively. In situ hybridization shows distinct localizations of the prepro-NPB mRNA in mouse brain, i.e., in paraventricular hypothalamic nucleus, hippocampus, and several nuclei in midbrain and brainstem. Intracerebroventricular (i.c.v.) injection of NPB in mice induces hyperphagia during the first 2 h, followed by hypophagia. Intracerebroventricular injection of NPB produces analgesia to s.c. formalin injection in rats. Through EST database searches, we identified a putative paralogous peptide. This peptide, termed neuropeptide W (NPW), also has an N-terminal tryptophan residue. Synthetic human NPW binds and activates human GPR7 or GPR8 with EC(50) values of 0.56 nM and 0.51 nM, respectively. The expression of NPW mRNA in mouse brain is confined to specific nuclei in midbrain and brainstem. These findings suggest diverse physiological functions of NPB and NPW in the central nervous system, acting as endogenous ligands on GPR7 andor GPR8.
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