Neuropeptides B/W receptor 1
Neuropeptides B/W receptor 1, also known as NPBW1 and GPR7, is a human protein encoded by the NPBWR1 gene.[5] As implied by its name, it and related gene NPBW2 (with which it shares 70% nucleotide identity) are transmembranes protein that bind Neuropeptide B (NPB) and Neuropeptide W (NPW), both proteins expressed strongly in parts of the brain that regulate stress and fear including the extended amygdala and stria terminalis. When originally discovered in 1995, these receptors had no known ligands ("orphan receptors") and were called GPR7 and GPR8,[6] but at least three groups in the early 2000s independently identified their endogenous ligands, triggering the name change in 2005.[7]
Structure
NPBW1 has seven transmembrane domains, which it unsurprisingly shares with NPBWR2, but also a family of somatostatin and opioid receptors,[8] and like these proteins couple to Gi-class G proteins.[9]
Functions
In rodent models, NPBWR1 is over-expressed in Schwann cells associated with neuropathic pain, suggesting it inhibits inflammatory pain responses.[10] Mice without NPBW1 exhibited a stronger hostile reaction to intruders, suggesting NPBW1 has a role in stress responses.[11] Early studies indicated that NPB and NPW had a complex effect on appetite, but generally led to anorexia.[12] Similarly, male rats lacking NPBWR1 exhibited hyperphagia and adult-onset obesity, though why female rats are unaffected is unknown.[13] Researchers speculated that activating these pathways might decrease obesity, and synthesized a small-molecule ligand that is capable of stimulating both receptors at low concentrations.[14]
References
- GRCh38: Ensembl release 89: ENSG00000288611 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000033774 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: NPBWR1 neuropeptides B/W receptor 1".
- O’Dowd B. F., Scheideler M. A., Nguyen T., Cheng R., Rasmussen J. S., Marchese A., et al. (1995). The cloning and chromosomal mapping of two novel human opioid-somatostatin-like receptor genes, GPR7 and GPR8, expressed in discrete areas of the brain. Genomics 28, 84–91. doi:10.1006/geno.1995.1109
- Davenport A., Singh G. (2005). Neuropeptide W/Neuropeptide B Receptors – NPBW1. IUPHAR Receptor database. doi:10.1786/080844542445
- Hondo M., Ishii M., Sakurai T. (2008). The NPB/NPW neuropeptide system and its role in regulating energy homeostasis, pain, and emotion. Results Probl. Cell Differ. 46, 239–256. doi:10.1007/400_2007_056
- Tanaka H., Yoshida T., Miyamoto N., Motoike T., Kurosu H., Shibata K., et al. (2003). Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. Proc. Natl. Acad. Sci. U.S.A. 100, 6251–6256. doi:10.1073/pnas.2233339100
- Zaratin P., Quattrini A., Previtali S., Comi G., Hervieu G., Scheideler M. (2005). Schwann cell overexpression of the GPR7 receptor in inflammatory and painful neuropathies. Mol. Cell. Neurosci. 28, 55–63 doi:10.1016/j.mcn.2004.08.010
- Nagata-Kuroiwa R., Furutani N., Hara J., Hondo M., Ishii M., Abe T., et al. (2011). Critical role of neuropeptides B/W receptor 1 signaling in social behavior and fear memory. PLoS ONE 6:e16972. doi:10.1371/journal.pone.0016972
- Tanaka H., Yoshida T., Miyamoto N., Motoike T., Kurosu H., Shibata K., et al. (2003). Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. Proc. Natl. Acad. Sci. U.S.A. 100, 6251–6256. doi:10.1073/pnas.2233339100
- Ishii M., Fei H., Friedman J. M. (2003). Targeted disruption of GPR7, the endogenous receptor for neuropeptides B and W, leads to metabolic defects and adult-onset obesity. Proc. Natl. Acad. Sci. U.S.A. 100, 10540–10545, doi:10.1073/pnas.1334189100
- Romero F. A., Hastings N. B., Moningka R., Guo Z., Wang M., Di Salvo J., et al. (2012). The discovery of potent antagonists of NPBWR1 (GPR7). Bioorg. Med. Chem. Lett. 22, 1014–1018. doi:10.1016/j.bmcl.2011.11.126
Further reading
- O'Dowd BF, Scheideler MA, Nguyen T, et al. (1995). "The cloning and chromosomal mapping of two novel human opioid-somatostatin-like receptor genes, GPR7 and GPR8, expressed in discrete areas of the brain". Genomics. 28 (1): 84–91. doi:10.1006/geno.1995.1109. PMID 7590751.
- Fujii R, Yoshida H, Fukusumi S, et al. (2002). "Identification of a neuropeptide modified with bromine as an endogenous ligand for GPR7". J. Biol. Chem. 277 (37): 34010–6. doi:10.1074/jbc.M205883200. PMID 12118011.
- Shimomura Y, Harada M, Goto M, et al. (2002). "Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8". J. Biol. Chem. 277 (39): 35826–32. doi:10.1074/jbc.M205337200. PMID 12130646.
- Brezillon S, Lannoy V, Franssen JD, et al. (2003). "Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8". J. Biol. Chem. 278 (2): 776–83. doi:10.1074/jbc.M206396200. PMID 12401809.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Tanaka H, Yoshida T, Miyamoto N, et al. (2003). "Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8". Proc. Natl. Acad. Sci. U.S.A. 100 (10): 6251–6. doi:10.1073/pnas.0837789100. PMC 156358. PMID 12719537.
- Zaratin PF, Quattrini A, Previtali SC, et al. (2005). "Schwann cell overexpression of the GPR7 receptor in inflammatory and painful neuropathies". Mol. Cell. Neurosci. 28 (1): 55–63. doi:10.1016/j.mcn.2004.08.010. PMID 15607941. S2CID 40483027.
- Mazzocchi G, Rebuffat P, Ziolkowska A, et al. (2005). "G protein receptors 7 and 8 are expressed in human adrenocortical cells, and their endogenous ligands neuropeptides B and w enhance cortisol secretion by activating adenylate cyclase- and phospholipase C-dependent signaling cascades". J. Clin. Endocrinol. Metab. 90 (6): 3466–71. doi:10.1210/jc.2004-2132. PMID 15797961.
- Cottrell S, Jung K, Kristiansen G, et al. (2007). "Discovery and validation of 3 novel DNA methylation markers of prostate cancer prognosis". J. Urol. 177 (5): 1753–8. doi:10.1016/j.juro.2007.01.010. PMID 17437806.
External links
- "Neuropeptide B/W Receptors: NPBW1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.