NPBW2 receptor | Neuropeptide W/neuropeptide B receptors | IUPHAR/BPS Guide to PHARMACOLOGY

NPBW2 receptor

Target id: 304

Nomenclature: NPBW2 receptor

Family: Neuropeptide W/neuropeptide B receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for NPBW2 receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 333 20q13.3 NPBWR2 neuropeptides B and W receptor 2 6
Previous and Unofficial Names
GPR8 | G protein-coupled receptor 8 | neuropeptides B/W receptor 2
Database Links
Specialist databases
GPCRDB npbw2_human (Hs)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
neuropeptide B-23 {Sp: Human}
neuropeptide B-29 {Sp: Human}
neuropeptide B-23 {Sp: Mouse}
neuropeptide B-29 {Sp: Mouse}
neuropeptide B-23 {Sp: Rat}
neuropeptide B-29 {Sp: Rat}
neuropeptide W-23 {Sp: Human}
neuropeptide W-30 {Sp: Human} , neuropeptide W-30 {Sp: Mouse}
neuropeptide W-23 {Sp: Mouse, Rat}
neuropeptide W-30 {Sp: Rat}
Potency order of endogenous ligands (Human)
neuropeptide W-23 (NPW, Q8N729) > neuropeptide W-30 (NPW, Q8N729) > neuropeptide B-29 (NPB, Q8NG41) > neuropeptide B-23 (NPB, Q8NG41)  [1]

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Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]NPW-23 (human) Hs Agonist 7.7 pKd 7
pKd 7.7 (Kd 1.99x10-8 M) [7]
neuropeptide W-23 {Sp: Human} Hs Full agonist 9.6 pIC50 1
pIC50 9.6 [1]
neuropeptide W-30 {Sp: Human} Hs Full agonist 9.4 pIC50 1
pIC50 9.4 [1]
neuropeptide B-29 {Sp: Human} Hs Full agonist 9.0 pIC50 1
pIC50 9.0 [1]
neuropeptide B-23 {Sp: Human} Hs Full agonist 8.4 pIC50 1
pIC50 8.4 [1]
Agonist Comments
The potency data above is found from several binding assays where the experimental conditions may not be consistent.
Results from functional studies give the rank order of affinity as:
NPW-23 > NPW-30 > NPB-29 > NPB-23 [1].

Deletion of the first tryptophan residue in both peptides results in significant reduction in potency suggesting that the N-terminus is involved in receptor binding and signal transduction.
These peptides do not share any obvious homology to known peptides and are both equipotent at NPBW1 as well as to its human homologue NPBW2.
These peptides also share high homology with other species such as rat and mouse.
Immunocytochemical localisation studies have reported the presence of these peptides in discrete regions of the central nervous system [2-3]. In the periphery, NPW-like immunoreactivity has been localised to the renal glomeruli, as well as the endothelium of both the left internal mammary artery and the endocardium. It has yet to be determined whether NPB or NPW circulate in human plasma.

The de-brominated forms of the endogenous ligands neuropeptide B-23 and neuropeptide B-29, des-Br-neuropeptide B-29 and des-Br-neuropeptide-23 were not found to be major components of bovine hypothalamus [4].
Antagonist Comments
No antagonists are currently available for NPBW2.
Allosteric Modulator Comments
It is currently unknown whether there are allosteric regulators of NPBW2.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Comments:  NPB has been shown to stimulate the Gq/11 phospholipase C pathway [5]. However, it has not been conclusively determined whether this is through NPBW2 activation or via another receptor.
References:  1,7-8
Tissue Distribution
Hippocampus, caudate nucleus, amygdala > thalamus, pituitary gland, adrenal gland, lymph node > corpus callosum, substantia nigra, cerebellum, spleen, fetal spleen, peripheral blood leukocytes, fetal kidney, testis, lung, lung carcinoma, colon, rectum, skin.
Species:  Human
Technique:  RT-PCR
References:  1
Zona glomerulosa (ZG) and zona fasciculata-reticularis (ZF/R) cells of the adrenal cortex.
Species:  Human
Technique:  RT-PCR.
References:  5
Functional Assays
Melanophore aggregation assay.
Species:  Human
Tissue:  Xenopus laevis melanophores transfected with the NPWB2 receptor
Response measured:  Aggregation of melanosomes.
References:  8
Measurement of cAMP levels in CHO cells transfected with the human NPBW2 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP production.
References:  1,7
Physiological Functions
Enhanced cortisol secretion.
Species:  Human
Tissue:  Adrenal gland (zona fasciculata and reticularis cells, in vitro).
References:  5
General Comments
The gene encoding NPBW2 has not yet been identified in rat or mouse.

References

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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: 776-783. [PMID:12401809]

2. Dun SL, Brailoiu GC, Mizuo K, Yang J, Chang JK, Dun NJ. (2005) Neuropeptide B immunoreactivity in the central nervous system of the rat. Brain Res., 1045: 157-163. [PMID:15910774]

3. Dun SL, Brailoiu GC, Yang J, Chang JK, Dun NJ. (2003) Neuropeptide W-immunoreactivity in the hypothalamus and pituitary of the rat. Neurosci Lett., 349: 71-74. [PMID:12946555]

4. Fujii R, Yoshida H, Fukusumi S, Habata Y, Hosoya M, Kawamata Y, Yano T, Hinuma S, Kitada C, Asami T, Mori M, Fujisawa Y, Fujino M. (2002) Identification of a neuropeptide modified with bromine as an endogenous ligand for GPR7. J Biol Chem., 277: 34010-34016. [PMID:12118011]

5. 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: 3466-3471. [PMID:15797961]

6. O'Dowd BF, Scheideler MA, Nguyen T, Cheng R, Rasmussen JS, Marchese A, Zastawny R, Heng HH, Tsui LC, Shi X 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. [PMID:7590751]

7. Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y, Abe M, Watanabe T, Asami T, Kitada C, Mori M, Onda H, Fujino M. (2002) Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8. J Biol Chem., 277: 35826-35832. [PMID:12130646]

8. Tanaka H, Yoshida T, Miyamoto N, Motoike T, Kurosu H, Shibata K, Yamanaka A, Williams SC, Richardson JA, Tsujino N, Garry MG, Lerner MR, King DS, O'Dowd BF, Sakurai T, Yanagisawa M. (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. [PMID:12719537]

Contributors

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How to cite this page

Anthony P. Davenport, Gurminder Singh.
Neuropeptide W/neuropeptide B receptors: NPBW2 receptor. Last modified on 20/02/2018. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=304.