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NPFF2 receptor

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Target not currently curated in GtoImmuPdb

Target id: 301

Nomenclature: NPFF2 receptor

Family: Neuropeptide FF/neuropeptide AF receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 522 4q13.3 NPFFR2 neuropeptide FF receptor 2 2,4
Mouse 7 417 5 E1 Npffr2 neuropeptide FF receptor 2
Rat 7 417 14p22 Npffr2 neuropeptide FF receptor 2 2
Previous and Unofficial Names Click here for help
F8Famide receptor | GPR74 [2] | NPGPR | G protein-coupled receptor 74
Database Links Click here for help
Specialist databases
GPCRDB npff2_human (Hs), npff2_mouse (Mm), npff2_rat (Rn)
Other databases
ChEMBL Target CHEMBL5952 (Hs), CHEMBL4523416 (Mm), CHEMBL3425 (Rn)
Ensembl Gene ENSG00000056291 (Hs), ENSMUSG00000035528 (Mm), ENSRNOG00000003067 (Rn)
Entrez Gene 10886 (Hs), 104443 (Mm), 78964 (Rn)
Human Protein Atlas ENSG00000056291 (Hs)
KEGG Gene hsa:10886 (Hs), mmu:104443 (Mm), rno:78964 (Rn)
OMIM 607449 (Hs)
Pharos Q9Y5X5 (Hs)
RefSeq Nucleotide NM_004885 (Hs), NM_053036 (Hs), NM_001144756 (Hs), NM_133192 (Mm), NM_023980 (Rn)
RefSeq Protein NP_001138228 (Hs), NP_444264 (Hs), NP_004876 (Hs), NP_573455 (Mm), NP_076470 (Rn)
UniProtKB Q9Y5X5 (Hs), Q924H0 (Mm), Q9EQD2 (Rn)
Wikipedia NPFFR2 (Hs)
Natural/Endogenous Ligands Click here for help
neuropeptide AF {Sp: Human} , neuropeptide AF {Sp: Mouse} , neuropeptide AF {Sp: Rat}
neuropeptide FF {Sp: Human, Mouse, Rat}
neuropeptide SF {Sp: Human}
RFRP-1 {Sp: Human}
RFRP-3 {Sp: Human}
Comments: Neuropeptide AF is the most potent endogenous agonist
Potency order of endogenous ligands (Human)
neuropeptide AF (NPFF, O15130), neuropeptide FF (NPFF, O15130) > PrRP-31 (PRLH, P81277) > FMRF, QRFP43 (43RFa) (QRFP, P83859) > neuropeptide SF (NPFF, O15130)  [5]

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]EYF Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 10.2 pKd 15
⤷ pKd 10.2 (Kd 6.3x10-11 M) [15]
[3H]EYF Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.3 pKd 25
⤷ pKd 9.3 (Kd 5.4x10-10 M) [25]
dNPA Peptide Hs Full agonist 10.6 pKi 22
⤷ pKi 10.6 (Ki 2.7x10-11 M) [22]
neuropeptide FF {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 9.7 pKi 7,14
⤷ pKi 9.7 [7,14]
EFWSLAAPQRF-NH2 Peptide Click here for species-specific activity table Hs Full agonist 9.6 pKi 15
⤷ pKi 9.6 [15]
1DMe Peptide Click here for species-specific activity table Hs Full agonist 8.5 – 9.7 pKi 2,7,15
⤷ pKi 8.5 – 9.7 [2,7,15]
pancreatic polypeptide {Sp: European common frog} Peptide Click here for species-specific activity table Hs Full agonist 8.1 – 8.2 pKi 2,14
⤷ pKi 8.1 – 8.2 [2,14]
Y-RFRP-3 Peptide Click here for species-specific activity table Hs Full agonist 8.0 pKi 7,15
⤷ pKi 8.0 [7,15]
RFRP-3 {Sp: Human} Peptide Click here for species-specific activity table Hs Full agonist 7.8 pKi 7,15
⤷ pKi 7.8 [7,15]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
RF9 Peptide Click here for species-specific activity table Hs Antagonist 7.1 pKi 23
⤷ pKi 7.1 [23]
BIBP3226 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 – 7.1 pKi 2,14
⤷ pKi 5.9 – 7.1 [2,14]
compound 46 [PMID: 25268943] Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.8 pKi 9
⤷ pKi 5.8 (Ki 1.426x10-6 M) [9]
Description: Binding affinity.
Antagonist Comments
BIBP3226 is also a selective antagonist of NPY1 receptors.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Calcium channel
Other - See Comments
Comments:  Reactivation of phospholipase C stimulated by carbachol in SH-SY5Y cells.
References:  15-16
Tissue Distribution Click here for help
Amygdala > caudate putamen > whole brain > hippocampus > pituitary > small intestine, spleen > fetal kidney > thalamus, hypothalamus > fetal brain, fetal liver, kidney, lung, pancreas, spinal cord, skeletal muscle, substantia nigra.
Species:  Human
Technique:  RT-PCR.
References:  2
Brain.
Species:  Mouse
Technique:  Radioligand binding.
References:  6
Brain.
Species:  Rat
Technique:  Radioligand binding.
References:  6
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP levels in CHO cells transfected with the human NPFF2 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-induced cAMP formation.
References:  4
Measurement of cAMP levels in HEK 293 cells transfected with the human NPFF2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of forskolin-induced cAMP formation.
References:  4
Measurement of Ca2+ levels in SH-SY5Y cells transfected with the human NPFF2 receptor.
Species:  Human
Tissue:  SH-SY5Y cells.
Response measured:  Ani-opioid effects on Ca2+ mobilisation.
References:  16
Measurement of [35S]GTPγS binding in CHO cells transfected with the human NPFF2 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  [35S]GTPγS binding.
References:  5
Measurement of [35S]GTPγS binding stimulated by NPFF2 receptors in rat spinal cord.
Species:  Rat
Tissue:  Spinal cord.
Response measured:  [35S]GTPγS binding.
References:  8
Measurement of intracellular Ca2+ levels in rat dorsal root ganglion neurons endogenously expressing the NPFF2 receptor.
Species:  Rat
Tissue:  Dorsal root ganglion neurons.
Response measured:  Modulation of intracellular Ca2+ levels.
References:  19
Measurement of intracellular Ca2+ levels in rat dorsal raphe neurons endogenously expressing the NPFF2 receptor.
Species:  Rat
Tissue:  Dorsal raphe neurons.
Response measured:  Anti-opioid effects on Ca2+ levels.
References:  21
Physiological Functions Click here for help
Modulation of opioid nociception.
Species:  Mouse
Tissue:  Brain and spinal cord.
References:  18
Thermoregulation.
Species:  Mouse
Tissue:  Brain.
References:  3
Modulation of arterial blood pressure.
Species:  Rat
Tissue:  Heart.
References:  1,20
Modulation of food intake.
Species:  Rat
Tissue:  In vivo.
References:  10,17,24
Modulation of adipocyte metabolism.
Species:  Human
Tissue:  Adipose tissue.
References:  11
Modulation of locomotion induced by morphine.
Species:  Rat
Tissue:  Ventral tegmental area.
References:  13
Modulation of conditioned place preference to morphine.
Species:  Mouse
Tissue:  Brain.
References:  12

References

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1. Allard M, Labrouche S, Nosjean A, Laguzzi R. (1995) Mechanisms underlying the cardiovascular responses to peripheral administration of NPFF in the rat. J Pharmacol Exp Ther, 274 (1): 577-83. [PMID:7616447]

2. Bonini JA, Jones KA, Adham N, Forray C, Artymyshyn R, Durkin MM, Smith KE, Tamm JA, Boteju LW, Lakhlani PP et al.. (2000) Identification and characterization of two G protein-coupled receptors for neuropeptide FF. J Biol Chem, 275 (50): 39324-31. [PMID:11024015]

3. Desprat C, Zajac JM. (1997) Hypothermic effects of neuropeptide FF analogues in mice. Pharmacol Biochem Behav, 58 (2): 559-63. [PMID:9300619]

4. Elshourbagy NA, Ames RS, Fitzgerald LR, Foley JJ, Chambers JK, Szekeres PG, Evans NA, Schmidt DB, Buckley PT, Dytko GM et al.. (2000) Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor. J Biol Chem, 275 (34): 25965-71. [PMID:10851242]

5. Gouardères C, Mazarguil H, Mollereau C, Chartrel N, Leprince J, Vaudry H, Zajac JM. (2007) Functional differences between NPFF1 and NPFF2 receptor coupling: high intrinsic activities of RFamide-related peptides on stimulation of [35S]GTPgammaS binding. Neuropharmacology, 52 (2): 376-86. [PMID:17011599]

6. Gouardères C, Puget A, Zajac JM. (2004) Detailed distribution of neuropeptide FF receptors (NPFF1 and NPFF2) in the rat, mouse, octodon, rabbit, guinea pig, and marmoset monkey brains: a comparative autoradiographic study. Synapse, 51 (4): 249-69. [PMID:14696013]

7. Gouardères C, Quelven I, Mollereau C, Mazarguil H, Rice SQ, Zajac JM. (2002) Quantitative autoradiographic distribution of NPFF1 neuropeptide FF receptor in the rat brain and comparison with NPFF2 receptor by using [125I]YVP and [(125I]EYF as selective radioligands. Neuroscience, 115 (2): 349-61. [PMID:12421602]

8. Gouardères C, Zajac JM. (2007) Biochemical anti-opioid action of NPFF2 receptors in rat spinal cord. Neurosci Res, 58 (1): 91-4. [PMID:17337079]

9. Journigan VB, Mésangeau C, Vyas N, Eans SO, Cutler SJ, McLaughlin JP, Mollereau C, McCurdy CR. (2014) Nonpeptide small molecule agonist and antagonist original leads for neuropeptide FF1 and FF2 receptors. J Med Chem, 57 (21): 8903-27. [PMID:25268943]

10. Kotani M, Mollereau C, Detheux M, Le Poul E, Brézillon S, Vakili J, Mazarguil H, Vassart G, Zajac JM, Parmentier M. (2001) Functional characterization of a human receptor for neuropeptide FF and related peptides. Br J Pharmacol, 133 (1): 138-44. [PMID:11325803]

11. Lefrere I, De Coppet P, Camelin JC, Le Lay S, Mercier N, Elshourbagy N, Bril A, Berrebi-Bertrand I, Feve B, Krief S. (2002) Neuropeptide AF and FF modulation of adipocyte metabolism. Primary insights from functional genomics and effects on beta-adrenergic responsiveness. J Biol Chem, 277 (42): 39169-78. [PMID:12149260]

12. Marchand S, Betourne A, Marty V, Daumas S, Halley H, Lassalle JM, Zajac JM, Frances B. (2006) A neuropeptide FF agonist blocks the acquisition of conditioned place preference to morphine in C57Bl/6J mice. Peptides, 27 (5): 964-72. [PMID:16494968]

13. Marco N, Stinus L, Allard M, Le Moal M, Simonnet G. (1995) Neuropeptide FLFQRFamide receptors within the ventral mesenchephalon and dopaminergic terminal areas: localization and functional antiopioid involvement. Neuroscience, 64 (4): 1035-44. [PMID:7753374]

14. Mollereau C, Gouardères C, Dumont Y, Kotani M, Detheux M, Doods H, Parmentier M, Quirion R, Zajac JM. (2001) Agonist and antagonist activities on human NPFF(2) receptors of the NPY ligands GR231118 and BIBP3226. Br J Pharmacol, 133 (1): 1-4. [PMID:11325787]

15. Mollereau C, Mazarguil H, Marcus D, Quelven I, Kotani M, Lannoy V, Dumont Y, Quirion R, Detheux M, Parmentier M et al.. (2002) Pharmacological characterization of human NPFF(1) and NPFF(2) receptors expressed in CHO cells by using NPY Y(1) receptor antagonists. Eur J Pharmacol, 451 (3): 245-56. [PMID:12242085]

16. Mollereau C, Mazarguil H, Zajac JM, Roumy M. (2005) Neuropeptide FF (NPFF) analogs functionally antagonize opioid activities in NPFF2 receptor-transfected SH-SY5Y neuroblastoma cells. Mol Pharmacol, 67 (3): 965-75. [PMID:15608144]

17. Murase T, Arima H, Kondo K, Oiso Y. (1996) Neuropeptide FF reduces food intake in rats. Peptides, 17 (2): 353-4. [PMID:8801545]

18. Quelven I, Roussin A, Zajac JM. (2005) Comparison of pharmacological activities of Neuropeptide FF1 and Neuropeptide FF2 receptor agonists. Eur J Pharmacol, 508 (1-3): 107-14. [PMID:15680260]

19. Rebeyrolles S, Zajac JM, Roumy M. (1996) Neuropeptide FF reverses the effect of mu-opioid on Ca2+ channels in rat spinal ganglion neurones. Neuroreport, 7 (18): 2979-81. [PMID:9116223]

20. Roth BL, Disimone J, Majane EA, Yang HY. (1987) Elevation of arterial pressure in rats by two new vertebrate peptides FLFQPQRF-NH2 and AGEGLSSPFWSLAAPQRF-NH2 which are immunoreactive to FMRF-NH2 antiserum. Neuropeptides, 10 (1): 37-42. [PMID:3670567]

21. Roumy M, Zajac J. (1999) Neuropeptide FF selectively attenuates the effects of nociceptin on acutely dissociated neurons of the rat dorsal raphe nucleus. Brain Res, 845 (2): 208-14. [PMID:10536200]

22. Roussin A, Serre F, Gouardères C, Mazarguil H, Roumy M, Mollereau C, Zajac JM. (2005) Anti-analgesia of a selective NPFF2 agonist depends on opioid activity. Biochem Biophys Res Commun, 336 (1): 197-203. [PMID:16129413]

23. Simonin F, Schmitt M, Laulin JP, Laboureyras E, Jhamandas JH, MacTavish D, Matifas A, Mollereau C, Laurent P, Parmentier M et al.. (2006) RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia. Proc Natl Acad Sci USA, 103 (2): 466-71. [PMID:16407169]

24. Sunter D, Hewson AK, Lynam S, Dickson SL. (2001) Intracerebroventricular injection of neuropeptide FF, an opioid modulating neuropeptide, acutely reduces food intake and stimulates water intake in the rat. Neurosci Lett, 313 (3): 145-8. [PMID:11682148]

25. Talmont F, Garcia LP, Mazarguil H, Zajac JM, Mollereau C. (2009) Characterization of two novel tritiated radioligands for labelling Neuropeptide FF (NPFF(1) and NPFF(2)) receptors. Neurochem Int, 55 (8): 815-9. [PMID:19682524]

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