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]

NPBWR1
Identifiers
AliasesNPBWR1, GPR7, Neuropeptides B/W receptor 1, neuropeptides B and W receptor 1
External IDsOMIM: 600730 MGI: 891989 HomoloGene: 21096 GeneCards: NPBWR1
Gene location (Human)
Chr.Chromosome 8 (human)[1]
Band8q11.23Start52,938,431 bp[1]
End52,941,117 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

2831

226304

Ensembl

ENSG00000183729

ENSMUSG00000033774

UniProt

P48145

P49681

RefSeq (mRNA)

NM_005285

NM_010342

RefSeq (protein)

NP_005276

NP_034472

Location (UCSC)Chr 8: 52.94 – 52.94 MbChr 1: 5.91 – 5.92 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

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References
  1. GRCh38: Ensembl release 89: ENSG00000183729 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000033774 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: NPBWR1 neuropeptides B/W receptor 1".
  6. 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
  7. Davenport A., Singh G. (2005). Neuropeptide W/Neuropeptide B Receptors – NPBW1. IUPHAR Receptor database. doi:10.1786/080844542445
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
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