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NPFF1 receptor

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Target not currently curated in GtoImmuPdb

Target id: 300

Nomenclature: NPFF1 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 7 430 10q22.1 NPFFR1 neuropeptide FF receptor 1 1
Mouse 7 432 10 32.24 cM Npffr1 neuropeptide FF receptor 1
Rat 7 432 20q11 Npffr1 neuropeptide FF receptor 1 1
Previous and Unofficial Names Click here for help
GPR147 [1] | G protein-coupled receptor 147 | NPFF1 | RFamide-related peptide receptor OT7T022 | NPFF1R1 | OT7T022 [9] | GnIH-R | GnIH-R/RFRP-3
Database Links Click here for help
Specialist databases
GPCRdb npff1_human (Hs), npff1_rat (Rn)
Other databases
Alphafold Q9GZQ6 (Hs), Q9EP86 (Rn)
ChEMBL Target CHEMBL5951 (Hs), CHEMBL4571 (Rn)
Ensembl Gene ENSG00000148734 (Hs), ENSMUSG00000020090 (Mm), ENSRNOG00000000559 (Rn)
Entrez Gene 64106 (Hs), 237362 (Mm), 64107 (Rn)
Human Protein Atlas ENSG00000148734 (Hs)
KEGG Gene hsa:64106 (Hs), mmu:237362 (Mm), rno:64107 (Rn)
OMIM 607448 (Hs)
Pharos Q9GZQ6 (Hs)
RefSeq Nucleotide NM_022146 (Hs), NM_001177511 (Mm), NM_022291 (Rn)
RefSeq Protein NP_071429 (Hs), NP_001170982 (Mm), NP_071627 (Rn)
UniProtKB Q9GZQ6 (Hs), Q9EP86 (Rn)
Wikipedia NPFFR1 (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} , neuropeptide SF {Sp: Mouse} , neuropeptide SF {Sp: Rat}
RFRP-1 {Sp: Human}
RFRP-3 {Sp: Human}
Comments: Neuropeptide FF is the most potent endogenous agonist
Potency order of endogenous ligands (Human)
RFRP-1 (NPVF, Q9HCQ7) > RFRP-3 (NPVF, Q9HCQ7) > FMRFneuropeptide FF (NPFF, O15130) > neuropeptide AF (NPFF, O15130) > neuropeptide SF (NPFF, O15130), QRFP43 (43RFa) (QRFP, P83859), PrRP-31 (PRLH, P81277)  [5]

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]Y-RFRP-3 Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.7 pKd 7
⤷ pKd 9.7 (Kd 8x10-9 M) [7]
[125I]1DMe Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.9 pKd 1
⤷ pKd 8.9 [1]
[3H]NPVF Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.6 pKd 28
⤷ pKd 8.6 (Kd 2.65x10-9 M) [28]
Y-RFRP-3 Peptide Click here for species-specific activity table Hs Full agonist 9.4 pKi 7,18
⤷ pKi 9.4 [7,18]
RFRP-3 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 9.2 – 9.3 pKi 7-8,18
⤷ pKi 9.2 – 9.3 [7-8,18]
neuropeptide FF {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.5 – 9.9 pKi 5,7,18
⤷ pKi 8.5 – 9.9 [5,7,18]
1DMe Peptide Click here for species-specific activity table Hs Full agonist 8.1 – 9.0 pKi 1,5,7
⤷ pKi 8.1 – 9.0 [1,5,7]
EFWSLAAPQRF-NH2 Peptide Click here for species-specific activity table Hs Full agonist 7.3 pKi 7,18
⤷ pKi 7.3 [7,18]
pancreatic polypeptide {Sp: European common frog} Peptide Click here for species-specific activity table Hs Partial agonist 5.3 pKi 1,7
⤷ pKi 5.3 [1,7]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BIBP3226 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.0 – 7.8 pKi 1,7,18
⤷ pKi 7.0 – 7.8 [1,7,18]
RF9 Peptide Click here for species-specific activity table Hs Antagonist 7.2 pKi 24
⤷ pKi 7.2 [24]
compound 46 [PMID: 25268943] Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 11
⤷ pKi 7.1 (Ki 8.1x10-8 M) [11]
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.
References:  14,18
Tissue Distribution Click here for help
Hypothalamus.
Species:  Human
Technique:  Immunohistochemistry.
References:  4
Spinal cord > hippocampus > amygdala > thalamus > whole brain, hypothalamus > cerebellum > caudate putamen > substantia nigra > spleen > lung > fetal lung > fetal brain > small intestine > pituitary, fetal kidney > kidney, stomach, skeletal muscle.
Species:  Human
Technique:  RT-PCR.
References:  1
Pituitary.
Species:  Human
Technique:  In situ hybridization.
References:  32
Brain.
Species:  Mouse
Technique:  Radioligand binding.
References:  6
Brain.
Species:  Rat
Technique:  Radioligand binding.
References:  6
Functional Assays Click here for help
Measurement of cAMP levels in CHO cells transfected with the human NPFF1 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-induced cAMP accumulation.
References:  9
Measurement of Ca2+ levels in SH-SY5Y cells transfected with the human NPFF1 receptor.
Species:  Human
Tissue:  SH-SY5Y cells.
Response measured:  Modulation of Ca+ levels.
References:  14
Measurement of [35S]GTPγS binding in CHO cells transfected with the human NPFF1 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  [35S]GTPγS binding.
References:  5
Measurement of Ca2+ levels in rat periventricular hypothalamic neurons endogenously expressing the NPFF1 receptor.
Species:  Rat
Tissue:  Periventricular hypothalamic neurons.
Response measured:  Anti-opioid effects.
References:  19
Measurement of cAMP levels in CHO cells transfected with the rat NPFF1 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-induced cAMP accumulation.
References:  17
Measurement of cAMP levels in LβT2 cells.
Species:  Mouse
Tissue:  LβT2 cells.
Response measured:  Inhibition of GnRH or forskolin-induced cAMP accumulation.
References:  26
Physiological Functions Click here for help
Opioid nociception modulation.
Species:  Mouse
Tissue:  In vivo (nervous tissue).
References:  22
Thermoregulation.
Species:  Mouse
Tissue:  In vivo
References:  22
Regulation of stress responses
Species:  Rat
Tissue:  In vivo
References:  15
Regulation of reproductive behaviour
Species:  Rat
Tissue:  In vivo
References:  10
Regulation of hypothalamic-pituitary-gonadal axis. Note that this regulatory function has also been demonstrated in macaque, ovine, bovine, hamster, mouse and rat tissues.
Species:  Human
Tissue:  In vivo, brain, pituitary
References:  2-3,10,12-13,16,20-21,23,25-26,29-33
Regulation of stress responses.
Species:  Mouse
Tissue:  In vitro
References:  27

References

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1. 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]

2. Clarke IJ, Sari IP, Qi Y, Smith JT, Parkington HC, Ubuka T, Iqbal J, Li Q, Tilbrook A, Morgan K et al.. (2008) Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion. Endocrinology, 149 (11): 5811-21. [PMID:18617613]

3. Ducret E, Anderson GM, Herbison AE. (2009) RFamide-related peptide-3, a mammalian gonadotropin-inhibitory hormone ortholog, regulates gonadotropin-releasing hormone neuron firing in the mouse. Endocrinology, 150 (6): 2799-804. [PMID:19131572]

4. Goncharuk V, Zeng Z, Wang R, MacTavish D, Jhamandas JH. (2004) Distribution of the neuropeptide FF1 receptor (hFF1) in the human hypothalamus and surrounding basal forebrain structures: immunohistochemical study. J Comp Neurol, 474 (4): 487-503. [PMID:15174068]

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. Hinuma S, Shintani Y, Fukusumi S, Iijima N, Matsumoto Y, Hosoya M, Fujii R, Watanabe T, Kikuchi K, Terao Y et al.. (2000) New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals. Nat Cell Biol, 2 (10): 703-8. [PMID:11025660]

10. Johnson MA, Tsutsui K, Fraley GS. (2007) Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat. Horm Behav, 51 (1): 171-80. [PMID:17113584]

11. 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]

12. Kadokawa H, Shibata M, Tanaka Y, Kojima T, Matsumoto K, Oshima K, Yamamoto N. (2009) Bovine C-terminal octapeptide of RFamide-related peptide-3 suppresses luteinizing hormone (LH) secretion from the pituitary as well as pulsatile LH secretion in bovines. Domest Anim Endocrinol, 36 (4): 219-24. [PMID:19328642]

13. Kaewwongse M, Takayanagi Y, Onaka T. (2011) Effects of RFamide-related peptide (RFRP)-1 and RFRP-3 on oxytocin release and anxiety-related behaviour in rats. J Neuroendocrinol, 23 (1): 20-7. [PMID:21029217]

14. Kersanté F, Mollereau C, Zajac JM, Roumy M. (2006) Anti-opioid activities of NPFF1 receptors in a SH-SY5Y model. Peptides, 27 (5): 980-9. [PMID:16488058]

15. Kirby ED, Geraghty AC, Ubuka T, Bentley GE, Kaufer D. (2009) Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. Proc Natl Acad Sci USA, 106 (27): 11324-9. [PMID:19541621]

16. Kriegsfeld LJ, Mei DF, Bentley GE, Ubuka T, Mason AO, Inoue K, Ukena K, Tsutsui K, Silver R. (2006) Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals. Proc Natl Acad Sci USA, 103 (7): 2410-5. [PMID:16467147]

17. Liu Q, Guan XM, Martin WJ, McDonald TP, Clements MK, Jiang Q, Zeng Z, Jacobson M, Williams Jr DL, Yu H et al.. (2001) Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception. J Biol Chem, 276 (40): 36961-9. [PMID:11481330]

18. 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]

19. 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]

20. Murakami M, Matsuzaki T, Iwasa T, Yasui T, Irahara M, Osugi T, Tsutsui K. (2008) Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats. J Endocrinol, 199 (1): 105-12. [PMID:18653621]

21. Pineda R, Garcia-Galiano D, Sanchez-Garrido MA, Romero M, Ruiz-Pino F, Aguilar E, Dijcks FA, Blomenröhr M, Pinilla L, van Noort PI et al.. (2010) Characterization of the potent gonadotropin-releasing activity of RF9, a selective antagonist of RF-amide-related peptides and neuropeptide FF receptors: physiological and pharmacological implications. Endocrinology, 151 (4): 1902-13. [PMID:20160130]

22. 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]

23. Sari IP, Rao A, Smith JT, Tilbrook AJ, Clarke IJ. (2009) Effect of RF-amide-related peptide-3 on luteinizing hormone and follicle-stimulating hormone synthesis and secretion in ovine pituitary gonadotropes. Endocrinology, 150 (12): 5549-56. [PMID:19808777]

24. 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]

25. Smith JT, Young IR, Veldhuis JD, Clarke IJ. (2012) Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system. Endocrinology, 153 (7): 3368-75. [PMID:22549225]

26. Son YL, Ubuka T, Millar RP, Kanasaki H, Tsutsui K. (2012) Gonadotropin-inhibitory hormone inhibits GnRH-induced gonadotropin subunit gene transcriptions by inhibiting AC/cAMP/PKA-dependent ERK pathway in LβT2 cells. Endocrinology, 153 (5): 2332-43. [PMID:22374973]

27. Son YL, Ubuka T, Narihiro M, Fukuda Y, Hasunuma I, Yamamoto K, Belsham DD, Tsutsui K. (2014) Molecular basis for the activation of gonadotropin-inhibitory hormone gene transcription by corticosterone. Endocrinology, 155 (5): 1817-26. [PMID:24552400]

28. 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]

29. Tsutsui K, Bentley GE, Bedecarrats G, Osugi T, Ubuka T, Kriegsfeld LJ. (2010) Gonadotropin-inhibitory hormone (GnIH) and its control of central and peripheral reproductive function. Front Neuroendocrinol, 31 (3): 284-95. [PMID:20211640]

30. Ubuka T, Inoue K, Fukuda Y, Mizuno T, Ukena K, Kriegsfeld LJ, Tsutsui K. (2012) Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone. Endocrinology, 153 (1): 373-85. [PMID:22045661]

31. Ubuka T, Lai H, Kitani M, Suzuuchi A, Pham V, Cadigan PA, Wang A, Chowdhury VS, Tsutsui K, Bentley GE. (2009) Gonadotropin-inhibitory hormone identification, cDNA cloning, and distribution in rhesus macaque brain. J Comp Neurol, 517 (6): 841-55. [PMID:19844991]

32. Ubuka T, Morgan K, Pawson AJ, Osugi T, Chowdhury VS, Minakata H, Tsutsui K, Millar RP, Bentley GE. (2009) Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis. PLoS ONE, 4 (12): e8400. [PMID:20027225]

33. Wu M, Dumalska I, Morozova E, van den Pol AN, Alreja M. (2009) Gonadotropin inhibitory hormone inhibits basal forebrain vGluT2-gonadotropin-releasing hormone neurons via a direct postsynaptic mechanism. J Physiol (Lond.), 587 (Pt 7): 1401-11. [PMID:19204051]

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