IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F43/2019.4

Neuropeptide FF/neuropeptide AF receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database



Catherine Mollereau-Manaute1, Lionel Moulédous2, Michel Roumy1, Kazuyoshi Tsutsui3, Takayoshi Ubuka4 and Jean-Marie Zajac1
  1. CNRS Toulouse, France
  2. Université Paul Sabatier, France
  3. Waseda University, Japan
  4. Monash University Malaysia, Malaysia


Abstract

The Neuropeptide FF receptor family contains two subtypes, NPFF1 and NPFF2 (provisional nomenclature [10]), which exhibit high affinities for neuropeptide FF (NPFF, O15130) and RFamide related peptides (RFRP: precursor gene symbol NPVF, Q9HCQ7). NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density in the superficial layers of the mammalian spinal cord where it is involved in nociception and modulation of opioid functions.

Contents

This is a citation summary for Neuropeptide FF/neuropeptide AF receptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.

GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those parts.

Please note that the database version for the citations given in GtoPdb are to the most recent preceding version in which the family or its subfamilies and targets were substantially changed. The links below are to the current version. If you need to consult the cited version, rather than the most recent version, please contact the GtoPdb curators.

Database links

Neuropeptide FF/neuropeptide AF receptors
http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=43
Introduction to Neuropeptide FF/neuropeptide AF receptors
http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=43
    Receptors
            NPFF1 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=300
            NPFF2 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=301

References

  1. Allard M, Labrouche S, Nosjean A and Laguzzi R. (1995) Mechanisms underlying the cardiovascular responses to peripheral administration of NPFF in the rat. J. Pharmacol. Exp. Ther. 274: 577-83 [PMID:7616447]
  2. Ballet S, Mauborgne A, Gouardères C, Bourgoin AS, Zajac JM, Hamon M and Cesselin F. (1999) The neuropeptide FF analogue, 1DME, enhances in vivo met-enkephalin release from the rat spinal cord. Neuropharmacology 38: 1317-24 [PMID:10471085]
  3. Bonini JA, Jones KA, Adham N, Forray C, Artymyshyn R, Durkin MM, Smith KE, Tamm JA, Boteju LW and Lakhlani PP et al.. (2000) Identification and characterization of two G protein-coupled receptors for neuropeptide FF. J. Biol. Chem. 275: 39324-31 [PMID:11024015]
  4. Clarke IJ, Sari IP, Qi Y, Smith JT, Parkington HC, Ubuka T, Iqbal J, Li Q, Tilbrook A and 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: 5811-21 [PMID:18617613]
  5. Desprat C and Zajac JM. (1997) Hypothermic effects of neuropeptide FF analogues in mice. Pharmacol. Biochem. Behav. 58: 559-63 [PMID:9300619]
  6. Dockray GJ. (2004) The expanding family of -RFamide peptides and their effects on feeding behaviour. Exp. Physiol. 89: 229-35 [PMID:15123557]
  7. Ducret E, Anderson GM and Herbison AE. (2009) RFamide-related peptide-3, a mammalian gonadotropin-inhibitory hormone ortholog, regulates gonadotropin-releasing hormone neuron firing in the mouse. Endocrinology 150: 2799-804 [PMID:19131572]
  8. Elhabazi K, Trigo JM, Mollereau C, Moulédous L, Zajac JM, Bihel F, Schmitt M, Bourguignon JJ, Meziane H and Petit-demoulière B et al.. (2012) Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments. Br. J. Pharmacol. 165: 424-35 [PMID:21718302]
  9. Elshourbagy NA, Ames RS, Fitzgerald LR, Foley JJ, Chambers JK, Szekeres PG, Evans NA, Schmidt DB, Buckley PT and 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: 25965-71 [PMID:10851242]
  10. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M and Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol. Rev. 57: 279-88 [PMID:15914470]
  11. Fukusumi S, Habata Y, Yoshida H, Iijima N, Kawamata Y, Hosoya M, Fujii R, Hinuma S, Kitada C and Shintani Y et al.. (2001) Characteristics and distribution of endogenous RFamide-related peptide-1. Biochim. Biophys. Acta 1540: 221-32 [PMID:11583817]
  12. Goncharuk V, Zeng Z, Wang R, MacTavish D and 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: 487-503 [PMID:15174068]
  13. Gouardères C, Mazarguil H, Mollereau C, Chartrel N, Leprince J, Vaudry H and 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: 376-86 [PMID:17011599]
  14. Gouardères C, Mollereau C, Tafani JA, Mazarguil H and Zajac JM. (2001) [(125)I]EYF: a new high affinity radioligand to neuropeptide FF receptors. Peptides 22: 623-9 [PMID:11311733]
  15. Gouardères C, Puget A and 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: 249-69 [PMID:14696013]
  16. Gouardères C, Quelven I, Mollereau C, Mazarguil H, Rice SQ and 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: 349-61 [PMID:12421602]
  17. Gouardères C, Sutak M, Zajac JM and Jhamandas K. (1993) Antinociceptive effects of intrathecally administered F8Famide and FMRFamide in the rat. Eur. J. Pharmacol. 237: 73-81 [PMID:8102975]
  18. Gouardères C and Zajac JM. (2007) Biochemical anti-opioid action of NPFF2 receptors in rat spinal cord. Neurosci. Res. 58: 91-4 [PMID:17337079]
  19. Hinuma S, Shintani Y, Fukusumi S, Iijima N, Matsumoto Y, Hosoya M, Fujii R, Watanabe T, Kikuchi K and Terao Y et al.. (2000) New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals. Nat. Cell Biol. 2: 703-8 [PMID:11025660]
  20. Jhamandas JH, MacTavish D and Harris KH. (2006) Neuropeptide FF (NPFF) control of magnocellular neurosecretory cells of the rat hypothalamic paraventricular nucleus (PVN). Peptides 27: 973-9 [PMID:16517015]
  21. Jhamandas JH, Simonin F, Bourguignon JJ and Harris KH. (2007) Neuropeptide FF and neuropeptide VF inhibit GABAergic neurotransmission in parvocellular neurons of the rat hypothalamic paraventricular nucleus. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292: R1872-80 [PMID:17289819]
  22. Johnson MA, Tsutsui K and 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: 171-80 [PMID:17113584]
  23. Kadokawa H, Shibata M, Tanaka Y, Kojima T, Matsumoto K, Oshima K and 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: 219-24 [PMID:19328642]
  24. Kaewwongse M, Takayanagi Y and 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: 20-7 [PMID:21029217]
  25. Kersanté F, Mollereau C, Zajac JM and Roumy M. (2006) Anti-opioid activities of NPFF1 receptors in a SH-SY5Y model. Peptides 27: 980-9 [PMID:16488058]
  26. Kersanté F, Wang JY, Chen JC, Mollereau C and Zajac JM. (2011) Anti-opioid effects of neuropeptide FF receptors in the ventral tegmental area. Neurosci. Lett. 488: 305-9 [PMID:21111027]
  27. Kirby ED, Geraghty AC, Ubuka T, Bentley GE and Kaufer D. (2009) Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. Proc. Natl. Acad. Sci. U.S.A. 106: 11324-9 [PMID:19541621]
  28. Kotani M, Mollereau C, Detheux M, Le Poul E, Brézillon S, Vakili J, Mazarguil H, Vassart G, Zajac JM and Parmentier M. (2001) Functional characterization of a human receptor for neuropeptide FF and related peptides. Br. J. Pharmacol. 133: 138-44 [PMID:11325803]
  29. Kriegsfeld LJ, Mei DF, Bentley GE, Ubuka T, Mason AO, Inoue K, Ukena K, Tsutsui K and Silver R. (2006) Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals. Proc. Natl. Acad. Sci. U.S.A. 103: 2410-5 [PMID:16467147]
  30. Lameh J, Bertozzi F, Kelly N, Jacobi PM, Nguyen D, Bajpai A, Gaubert G, Olsson R and Gardell LR. (2010) Neuropeptide FF receptors have opposing modulatory effects on nociception. J. Pharmacol. Exp. Ther. 334: 244-54 [PMID:20354177]
  31. Lefrere I, De Coppet P, Camelin JC, Le Lay S, Mercier N, Elshourbagy N, Bril A, Berrebi-Bertrand I, Feve B and 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: 39169-78 [PMID:12149260]
  32. Liu Q, Guan XM, Martin WJ, McDonald TP, Clements MK, Jiang Q, Zeng Z, Jacobson M, Williams Jr DL and Yu H et al.. (2001) Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception. J. Biol. Chem. 276: 36961-9 [PMID:11481330]
  33. Marchand S, Betourne A, Marty V, Daumas S, Halley H, Lassalle JM, Zajac JM and Frances B. (2006) A neuropeptide FF agonist blocks the acquisition of conditioned place preference to morphine in C57Bl/6J mice. Peptides 27: 964-72 [PMID:16494968]
  34. Marco N, Stinus L, Allard M, Le Moal M and Simonnet G. (1995) Neuropeptide FLFQRFamide receptors within the ventral mesenchephalon and dopaminergic terminal areas: localization and functional antiopioid involvement. Neuroscience 64: 1035-44 [PMID:7753374]
  35. Mollereau C, Gouardères C, Dumont Y, Kotani M, Detheux M, Doods H, Parmentier M, Quirion R and Zajac JM. (2001) Agonist and antagonist activities on human NPFF(2) receptors of the NPY ligands GR231118 and BIBP3226. Br. J. Pharmacol. 133: 1-4 [PMID:11325787]
  36. Mollereau C, Mazarguil H, Marcus D, Quelven I, Kotani M, Lannoy V, Dumont Y, Quirion R, Detheux M and 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: 245-56 [PMID:12242085]
  37. Mollereau C, Mazarguil H, Zajac JM and Roumy M. (2005) Neuropeptide FF (NPFF) analogs functionally antagonize opioid activities in NPFF2 receptor-transfected SH-SY5Y neuroblastoma cells. Mol. Pharmacol. 67: 965-75 [PMID:15608144]
  38. Mollereau C, Roumy M and Zajac JM. (2005) Opioid-modulating peptides: mechanisms of action. Curr Top Med Chem 5: 341-355 [PMID:15857316]
  39. Moulédous L, Frances B and Zajac JM. (2010) Modulation of basal and morphine-induced neuronal activity by a NPFF(2) selective agonist measured by c-Fos mapping of the mouse brain. Synapse 64: 672-81 [PMID:20336629]
  40. Moulédous L, Froment C, Dauvillier S, Burlet-Schiltz O, Zajac JM and Mollereau C. (2012) GRK2 protein-mediated transphosphorylation contributes to loss of function of μ-opioid receptors induced by neuropeptide FF (NPFF2) receptors. J. Biol. Chem. 287: 12736-49 [PMID:22375000]
  41. Moulédous L, Mollereau C and Zajac JM. (2010) Opioid-modulating properties of the neuropeptide FF system. Biofactors 36: 423-9 [PMID:20803521]
  42. Murakami M, Matsuzaki T, Iwasa T, Yasui T, Irahara M, Osugi T and Tsutsui K. (2008) Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats. J. Endocrinol. 199: 105-12 [PMID:18653621]
  43. Murase T, Arima H, Kondo K and Oiso Y. (1996) Neuropeptide FF reduces food intake in rats. Peptides 17: 353-4 [PMID:8801545]
  44. Panula P, Kalso E, Nieminen M, Kontinen VK, Brandt A and Pertovaara A. (1999) Neuropeptide FF and modulation of pain. Brain Res. 848: 191-6 [PMID:10612711]
  45. Perry SJ, Yi-Kung Huang E, Cronk D, Bagust J, Sharma R, Walker RJ, Wilson S and Burke JF. (1997) A human gene encoding morphine modulating peptides related to NPFF and FMRFamide. FEBS Lett. 409: 426-30 [PMID:9224703]
  46. Pineda R, Garcia-Galiano D, Sanchez-Garrido MA, Romero M, Ruiz-Pino F, Aguilar E, Dijcks FA, Blomenröhr M, Pinilla L and 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: 1902-13 [PMID:20160130]
  47. Quelven I, Roussin A and Zajac JM. (2005) Comparison of pharmacological activities of Neuropeptide FF1 and Neuropeptide FF2 receptor agonists. Eur. J. Pharmacol. 508: 107-14 [PMID:15680260]
  48. Rebeyrolles S, Zajac JM and Roumy M. (1996) Neuropeptide FF reverses the effect of mu-opioid on Ca2+ channels in rat spinal ganglion neurones. Neuroreport 7: 2979-81 [PMID:9116223]
  49. Roth BL, Disimone J, Majane EA and 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: 37-42 [PMID:3670567]
  50. Roumy M, Garnier M and Zajac JM. (2003) Neuropeptide FF receptors 1 and 2 exert an anti-opioid activity in acutely dissociated rat dorsal raphe and periventricular hypothalamic neurones. Neurosci. Lett. 348: 159-62 [PMID:12932818]
  51. Roumy M, Lorenzo C, Mazères S, Bouchet S, Zajac JM and Mollereau C. (2007) Physical association between neuropeptide FF and micro-opioid receptors as a possible molecular basis for anti-opioid activity. J. Biol. Chem. 282: 8332-42 [PMID:17224450]
  52. Roumy M and Zajac J. (1999) Neuropeptide FF selectively attenuates the effects of nociceptin on acutely dissociated neurons of the rat dorsal raphe nucleus. Brain Res. 845: 208-14 [PMID:10536200]
  53. Roumy M and Zajac JM. (1998) Neuropeptide FF, pain and analgesia. Eur. J. Pharmacol. 345: 1-11 [PMID:9593588]
  54. Roussin A, Serre F, Gouardères C, Mazarguil H, Roumy M, Mollereau C and Zajac JM. (2005) Anti-analgesia of a selective NPFF2 agonist depends on opioid activity. Biochem. Biophys. Res. Commun. 336: 197-203 [PMID:16129413]
  55. Sari IP, Rao A, Smith JT, Tilbrook AJ and 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: 5549-56 [PMID:19808777]
  56. Simonin F, Schmitt M, Laulin JP, Laboureyras E, Jhamandas JH, MacTavish D, Matifas A, Mollereau C, Laurent P and 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. U.S.A. 103: 466-71 [PMID:16407169]
  57. Smith JT, Young IR, Veldhuis JD and Clarke IJ. (2012) Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system. Endocrinology 153: 3368-75 [PMID:22549225]
  58. Son YL, Ubuka T, Millar RP, Kanasaki H and 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: 2332-43 [PMID:22374973]
  59. Son YL, Ubuka T, Narihiro M, Fukuda Y, Hasunuma I, Yamamoto K, Belsham DD and Tsutsui K. (2014) Molecular basis for the activation of gonadotropin-inhibitory hormone gene transcription by corticosterone. Endocrinology 155: 1817-26 [PMID:24552400]
  60. Sunter D, Hewson AK, Lynam S and 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: 145-8 [PMID:11682148]
  61. Takeuchi T, Fujita A, Roumy M, Zajac JM and Hata F. (2001) Effect of 1DMe, a neuropeptide FF analog, on acetylcholine release from myenteric plexus of guinea pig ileum. Jpn. J. Pharmacol. 86: 417-22 [PMID:11569615]
  62. Talmont F, Garcia LP, Mazarguil H, Zajac JM and Mollereau C. (2009) Characterization of two novel tritiated radioligands for labelling Neuropeptide FF (NPFF(1) and NPFF(2)) receptors. Neurochem. Int. 55: 815-9 [PMID:19682524]
  63. Tsutsui K, Bentley GE, Bedecarrats G, Osugi T, Ubuka T and Kriegsfeld LJ. (2010) Gonadotropin-inhibitory hormone (GnIH) and its control of central and peripheral reproductive function. Front Neuroendocrinol 31: 284-95 [PMID:20211640]
  64. Ubuka T, Inoue K, Fukuda Y, Mizuno T, Ukena K, Kriegsfeld LJ and Tsutsui K. (2012) Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone. Endocrinology 153: 373-85 [PMID:22045661]
  65. Ubuka T, Lai H, Kitani M, Suzuuchi A, Pham V, Cadigan PA, Wang A, Chowdhury VS, Tsutsui K and Bentley GE. (2009) Gonadotropin-inhibitory hormone identification, cDNA cloning, and distribution in rhesus macaque brain. J. Comp. Neurol. 517: 841-55 [PMID:19844991]
  66. Ubuka T, Morgan K, Pawson AJ, Osugi T, Chowdhury VS, Minakata H, Tsutsui K, Millar RP and 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: e8400 [PMID:20027225]
  67. Ukena K, Iwakoshi E, Minakata H and Tsutsui K. (2002) A novel rat hypothalamic RFamide-related peptide identified by immunoaffinity chromatography and mass spectrometry. FEBS Lett. 512: 255-8 [PMID:11852091]
  68. Vilim FS, Aarnisalo AA, Nieminen ML, Lintunen M, Karlstedt K, Kontinen VK, Kalso E, States B, Panula P and Ziff E. (1999) Gene for pain modulatory neuropeptide NPFF: induction in spinal cord by noxious stimuli. Mol. Pharmacol. 55: 804-11 [PMID:10220558]
  69. Wu M, Dumalska I, Morozova E, van den Pol AN and Alreja M. (2009) Gonadotropin inhibitory hormone inhibits basal forebrain vGluT2-gonadotropin-releasing hormone neurons via a direct postsynaptic mechanism. J. Physiol. (Lond.) 587: 1401-11 [PMID:19204051]
  70. Yang HY, Fratta W, Majane EA and Costa E. (1985) Isolation, sequencing, synthesis, and pharmacological characterization of two brain neuropeptides that modulate the action of morphine. Proc. Natl. Acad. Sci. U.S.A. 82: 7757-61 [PMID:3865193]
  71. Yang HY and Iadarola MJ. (2006) Modulatory roles of the NPFF system in pain mechanisms at the spinal level. Peptides 27: 943-52 [PMID:16443306]
  72. Yoshida H, Habata Y, Hosoya M, Kawamata Y, Kitada C and Hinuma S. (2003) Molecular properties of endogenous RFamide-related peptide-3 and its interaction with receptors. Biochim. Biophys. Acta 1593: 151-7 [PMID:12581859]
  73. Zajac JM. (2001) Neuropeptide FF: new molecular insights. Trends Pharmacol. Sci. 22: 63 [PMID:11421201]