NDLI: Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8

Content Provider	PubMed Central
Author	Tanaka, Hirokazu Yoshida, Tetsuo Miyamoto, Norimasa Motoike, Toshiyuki Kurosu, Hiroshi Shibata, Kenji Yamanaka, Akihiro Williams, S. Clay Richardson, James A. Tsujino, Natsuko Garry, Mary G. Lerner, Michael R. King, David S. O'dowd, Brian F. Sakurai, Takeshi Yanagisawa, Masashi
Copyright Year	2003
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 (EC50) 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 EC50 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 and/or GPR8.
Related Links	http://dx.doi.org/10.1073/pnas.0837789100
Ending Page	6256
Page Count	6
Starting Page	6251
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	100
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2003-05-13
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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