PMID- 12719537 OWN - NLM STAT- MEDLINE DCOM- 20030701 LR - 20220318 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 100 IP - 10 DP - 2003 May 13 TI - Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. PG - 6251-6 AB - 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. FAU - Tanaka, Hirokazu AU - Tanaka H AD - Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75390-9050, USA. FAU - Yoshida, Tetsuo AU - Yoshida T FAU - Miyamoto, Norimasa AU - Miyamoto N FAU - Motoike, Toshiyuki AU - Motoike T FAU - Kurosu, Hiroshi AU - Kurosu H FAU - Shibata, Kenji AU - Shibata K FAU - Yamanaka, Akihiro AU - Yamanaka A FAU - Williams, S Clay AU - Williams SC FAU - Richardson, James A AU - Richardson JA FAU - Tsujino, Natsuko AU - Tsujino N FAU - Garry, Mary G AU - Garry MG FAU - Lerner, Michael R AU - Lerner MR FAU - King, David S AU - King DS FAU - O'Dowd, Brian F AU - O'Dowd BF FAU - Sakurai, Takeshi AU - Sakurai T FAU - Yanagisawa, Masashi AU - Yanagisawa M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030428 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Ligands) RN - 0 (NPBWR1 protein, human) RN - 0 (NPBWR2 protein, human) RN - 0 (NPW protein, human) RN - 0 (Neuropeptides) RN - 0 (Npbwr1 protein, mouse) RN - 0 (Npbwr1 protein, rat) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Receptors, Neuropeptide) RN - 0 (Recombinant Proteins) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Binding Sites MH - Cattle MH - Conserved Sequence MH - GTP-Binding Proteins/*metabolism MH - Humans MH - Ligands MH - Melanophores/physiology MH - Mice MH - Molecular Sequence Data MH - Neuropeptides/chemistry/genetics/*metabolism MH - Rats MH - Receptors, G-Protein-Coupled MH - Receptors, Neuropeptide/genetics/*metabolism MH - Recombinant Proteins/metabolism MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Transfection MH - Xenopus laevis MH - Zebrafish PMC - PMC156358 EDAT- 2003/04/30 05:00 MHDA- 2003/07/02 05:00 PMCR- 2003/11/13 CRDT- 2003/04/30 05:00 PHST- 2003/04/30 05:00 [pubmed] PHST- 2003/07/02 05:00 [medline] PHST- 2003/04/30 05:00 [entrez] PHST- 2003/11/13 00:00 [pmc-release] AID - 0837789100 [pii] AID - 7789 [pii] AID - 10.1073/pnas.0837789100 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2003 May 13;100(10):6251-6. doi: 10.1073/pnas.0837789100. Epub 2003 Apr 28.