The neuropeptide BW receptor 1 (NPBW1, provisional nomenclature [2]) is activated by two 23-amino-acid peptides, neuropeptide W (neuropeptide W-23 (NPW, Q8N729)) and neuropeptide B (neuropeptide B-23 (NPB, Q8NG41)) [3,12]. C-terminally extended forms of the peptides (neuropeptide W-30 (NPW, Q8N729) and neuropeptide B-29 (NPB, Q8NG41)) also activate NPBW1 [1]. Unique to both forms of neuropeptide B is the N-terminal bromination of the first tryptophan residue, and it is from this post-translational modification that the nomenclature NPB is derived. These peptides were first identified from bovine hypothalamus and therefore are classed as neuropeptides. Endogenous variants of the peptides without the N-terminal bromination, des-Br-neuropeptide B-23 (NPB, Q8NG41) and des-Br-neuropeptide B-29 (NPB, Q8NG41), were not found to be major components of bovine hypothalamic tissue extracts. The NPBW2 receptor is activated by the short and C-terminal extended forms of neuropeptide W and neuropeptide B [1].

Potency measurements were conducted with heterologously-expressed receptors with a range of 0.14-0.57 nM (NPBW1) and 0.98-21 nM (NPBW2). NPBW1^-/- mice show changes in social behavior, suggesting that the NPBW1 pathway may have an important role in the emotional responses of social interaction [9]. For a review of the contribution of neuropeptide B/W to social dominance, see Watanabe and Yamamoto, 2015 [14]. It has been reported that neuropeptide W may have a key role in the gating of stressful stimuli when mice are exposed to novel environments [8]. Two antagonists have been discovered and reported to have affinity for NPBW1, ML181 and ML250, the latter exhibiting improved selectivity (~100 fold) for NPBW1 compared to MCH1 receptors [4-5]. Computational insights into the binding of antagonists to this receptor have also been described [10-11].

* Key recommended reading is highlighted with an asterisk

* Sakurai T. (2013) NPBWR1 and NPBWR2: Implications in Energy Homeostasis, Pain, and Emotion. Front Endocrinol (Lausanne), 4: 23. [PMID:23515889]

* Singh G, Davenport AP. (2006) Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system. Br J Pharmacol, 148 (8): 1033-41. [PMID:16847439]

1. Brezillon S, Lannoy V, Franssen JD, Le Poul E, Dupriez V, Lucchetti J, Detheux M, Parmentier M. (2003) Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8. J Biol Chem, 278 (2): 776-83. [PMID:12401809]

2. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57 (2): 279-88. [PMID:15914470]

3. Fujii R, Yoshida H, Fukusumi S, Habata Y, Hosoya M, Kawamata Y, Yano T, Hinuma S, Kitada C, Asami T et al.. (2002) Identification of a neuropeptide modified with bromine as an endogenous ligand for GPR7. J Biol Chem, 277 (37): 34010-6. [PMID:12118011]

4. Guerrero M, Urbano M, Wang Z, Zhao J, Velaparthi S, Schaeffer MT, Brown SJ, Saldanha SA, Chase P, Ferguson J et al.. (2010) Optimization and Characterization of a Second Antagonist for G-protein Coupled Receptor 7 (GPR7). Probe Reports from the NIH Molecular Libraries Program,. [PMID:23762933]

5. Guerrero M, Urbano M, Wang Z, Zhao J, Velaparthi S, Schaeffer MT, Brown SJ, Saldanha SA, Chase P, Ferguson J et al.. (2010) Optimization and Characterization of an Antagonist for G-Protein Coupled Receptor 7 (GPR7). Probe Reports from the NIH Molecular Libraries Program,. [PMID:22834040]

6. Kanesaka M, Matsuda M, Hirano A, Tanaka K, Kanatani A, Tokita S. (2007) Development of a potent and selective GPR7 (NPBW1) agonist: a systematic structure-activity study of neuropeptide B. J Pept Sci, 13 (6): 379-85. [PMID:17486669]

7. Mazzocchi G, Rebuffat P, Ziolkowska A, Rossi GP, Malendowicz LK, Nussdorfer GG. (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. [PMID:15797961]

8. Motoike T, Long JM, Tanaka H, Sinton CM, Skach A, Williams SC, Hammer RE, Sakurai T, Yanagisawa M. (2016) Mesolimbic neuropeptide W coordinates stress responses under novel environments. Proc Natl Acad Sci USA, 113 (21): 6023-8. [PMID:27140610]

9. Nagata-Kuroiwa R, Furutani N, Hara J, Hondo M, Ishii M, Abe T, Mieda M, Tsujino N, Motoike T, Yanagawa Y et al.. (2011) Critical role of neuropeptides B/W receptor 1 signaling in social behavior and fear memory. PLoS ONE, 6 (2): e16972. [PMID:21390312]

10. Patra MC, Maharana J, Dehury B, De S. (2014) Computational insights into the binding mechanism of antagonists with neuropeptide B/W receptor 1. Mol Biosyst, 10 (8): 2236-46. [PMID:24938207]

11. Pawson AJ, Faccenda E, Maudsley S, Lu ZL, Naor Z, Millar RP. (2008) Mammalian type I gonadotropin-releasing hormone receptors undergo slow, constitutive, agonist-independent internalization. Endocrinology, 149 (3): 1415-22. [PMID:18039780]

12. Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y, Abe M, Watanabe T, Asami T, Kitada C, Mori 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. [PMID:12130646]

13. Singh G, Maguire JJ, Kuc RE, Fidock M, Davenport AP. (2004) Identification and cellular localisation of NPW1 (GPR7) receptors for the novel neuropeptide W-23 by [125I]-NPW radioligand binding and immunocytochemistry. Brain Res, 1017 (1-2): 222-6. [PMID:15261118]

14. Watanabe N, Yamamoto M. (2015) Neural mechanisms of social dominance. Front Neurosci, 9: 154. [PMID:26136644]

Subcommittee members: Anthony P. Davenport (Chairperson) Experimental Medicine and Immunotherapeutics University of Cambridge Addenbrooke’s Hospital Cambridge UK Janet J. Maguire Experimental Medicine and Immunotherapeutics University of Cambridge Addenbrooke’s Hospital Cambridge UK Gurminder Singh Clinical Pharmacology Unit University of Cambridge Level 6, Centre for Clinical Investigation Box 110, Addenbrooke's Hospital Cambridge, CB2 0QQ UK