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NOP Receptor Signaling Cascades

  • Kyle E. Parker
  • Michael R. BruchasEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 254)

Abstract

The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a G protein-coupled receptor with wide distribution throughout the peripheral and central nervous system. Similar to other opioid receptors, NOP receptors couple to intracellular second messengers and regulatory proteins to affect biological systems. In this chapter, we review the current literature for NOP signaling cascades including their role as classic GPCRs, the investigation of their kinase and arrestin signaling pathways, and the importance of examining biased signaling to critically evaluate the therapeutic potential of novel NOP agonists.

Keywords

Arrestin Bias G protein N/OFQ Nociceptin NOP receptors 

References

  1. Al-Hasani R, Bruchas MR (2011) Molecular mechanisms of opioid receptor-dependent signaling and behavior. J Am Soc Anesthesiol 115(6):1363–1381Google Scholar
  2. Armstead W (2002) NOC/oFQ activates PKC and generates superoxide to impair hypotensive cerebrovasodilation after hypoxia/ischemia. Med Sci Monit 8(1):BR0Google Scholar
  3. Armstead WM (2006) Differential activation of ERK, p38, and JNK MAPK by nociceptin/orphanin FQ in the potentiation of prostaglandin cerebrovasoconstriction after brain injury. Eur J Pharmacol 529(1–3):129–135CrossRefGoogle Scholar
  4. Asth L, Ruzza C, Malfacini D, Medeiros I, Guerrini R, Zaveri NT et al (2016) Beta-arrestin 2 rather than G protein efficacy determines the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands. Neuropharmacology 105:434–442PubMedPubMedCentralGoogle Scholar
  5. Barchfeld CC, Medzihradsky F (1984) Receptor-mediated stimulation of brain GTPase by opiates in normal and dependent rats. Biochem Biophys Res Commun 121:641–648CrossRefGoogle Scholar
  6. Beedle AM, McRory JE, Poirot O, Doering CJ, Altier C, Barrere C et al (2004) Agonist-independent modulation of N-type calcium channels by ORL1 receptors. Nat Neurosci 7(2):118CrossRefGoogle Scholar
  7. Bes B, Meunier JC (2003) Identification of a hexapeptide binding region in the nociceptin (ORL1) receptor by photo-affinity labelling with Ac-Arg-Bpa-Tyr-Arg-Trp-Arg-NH 2. Biochem Biophys Res Commun 310(3):992–1001CrossRefGoogle Scholar
  8. Blume AJ, Lichtshtein D, Boone G (1979) Coupling of opiate receptors to adenylate cyclase: requirement for Na+ and GTP. Proc Natl Acad Sci U S A 76(11):5626–5630CrossRefGoogle Scholar
  9. Bruchas MR, Chavkin C (2010) Kinase cascades and ligand-directed signaling at the kappa opioid receptor. Psychopharmacology 210(2):137–147CrossRefGoogle Scholar
  10. Bruchas MR, Land BB, Aita M, Xu M, Barot SK, Li S, Chavkin C (2007) Stress-induced p38 mitogen-activated protein kinase activation mediates κ-opioid-dependent dysphoria. J Neurosci 27(43):11614–11623CrossRefGoogle Scholar
  11. Bruchas MR, Schindler AG, Shankar H, Messinger DI, Miyatake M, Land BB et al (2011) Selective p38α MAPK deletion in serotonergic neurons produces stress resilience in models of depression and addiction. Neuron 71(3):498–511CrossRefGoogle Scholar
  12. Butour JL, Moisand C, Mazarguil H, Mollereau C, Meunier JC (1997) Recognition and activation of the opioid receptor-like ORL1 receptor by nociceptin, nociceptin analogs and opioids. Eur J Pharmacol 321(1):97–103CrossRefGoogle Scholar
  13. Chan AS, Wong YH (2000) Regulation of c-Jun N-terminal kinase by the ORL1 receptor through multiple G proteins. J Pharmacol Exp Ther 295(3):1094–1100PubMedGoogle Scholar
  14. Chan JS, Yung LY, Lee JW, Wu YL, Pei G, Wong YH (1998) Pertussis toxin-insensitive signaling of the ORL1 receptor: coupling to Gz and G16 proteins. J Neurochem 71(5):2203–2210CrossRefGoogle Scholar
  15. Chang SD, Bruchas MR (2014) Functional selectivity at GPCRs: new opportunities in psychiatric drug discovery. Neuropsychopharmacology 39(1):248CrossRefGoogle Scholar
  16. Chang SD, Mascarella SW, Spangler S, Gurevich VV, Navarro HA, Carroll FI, Bruchas MR (2015) Quantitative signaling and structure-activity analyses demonstrate functional selectivity at the nociceptin/orphanin FQ opioid receptor. Mol Pharmacol 88:502–511CrossRefGoogle Scholar
  17. Childers SR, Snyder SH (1978) Guanine nucleotides differentiate agonist and antagonist interactions with opiate receptors. Life Sci 23(7):759–761CrossRefGoogle Scholar
  18. Childers SR, Creese I, Snowman AM, Snyder SH (1979) Opiate receptor binding affected differentially by opiates and opioid peptides. Eur J Pharmacol 55(1):11–18CrossRefGoogle Scholar
  19. Connor M, Christie MJ (1998) Modulation of Ca2+ channel currents of acutely dissociated rat periaqueductal grey neurons. J Physiol 509(1):47–58CrossRefGoogle Scholar
  20. Connor M, Yoe A, Henderson G (1996) The effect of nociceptin on Ca2+ channel current and intracellular Ca2+ in the SH-SY5Y human neuroblastoma cell line. Br J Pharmacol 118(2):205–207CrossRefGoogle Scholar
  21. Corbani M, Gonindard C, Meunier JC (2004) Ligand-regulated internalization of the opioid receptor-like 1: a confocal study. Endocrinology 145(6):2876–2885CrossRefGoogle Scholar
  22. Dautzenberg FM, Wichmann J, Higelin J, Py-Lang G, Kratzeisen C, Malherbe P et al (2001) Pharmacological characterization of the novel nonpeptide orphanin FQ/nociceptin receptor agonist Ro 64-6198: rapid and reversible desensitization of the ORL1 receptor in vitro and lack of tolerance in vivo. J Pharmacol Exp Ther 298(2):812–819PubMedPubMedCentralGoogle Scholar
  23. Donica CL, Awwad HO, Thakker DR, Standifer KM (2013) Cellular mechanisms of nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor regulation and heterologous regulation by N/OFQ. Mol Pharmacol 83:907–918CrossRefGoogle Scholar
  24. Ferrari F, Cerlesi MC, Malfacini D, Asth L, Gavioli EC, Journigan BV et al (2016) In vitro functional characterization of novel nociceptin/orphanin FQ receptor agonists in recombinant and native preparations. Eur J Pharmacol 793:1–13PubMedPubMedCentralGoogle Scholar
  25. Ferrari F, Malfacini D, Journigan BV, Bird MF, Trapella C, Guerrini R et al (2017) In vitro pharmacological characterization of a novel unbiased NOP receptor-selective nonpeptide agonist AT-403. Pharmacol Res Perspect 5(4)CrossRefGoogle Scholar
  26. Fukuda K, Shoda T, Morikawa H, Kato S, Mori K (1997) Activation of mitogen-activated protein kinase by the nociceptin receptor expressed in Chinese hamster ovary cells. FEBS Lett 412(2):290–294CrossRefGoogle Scholar
  27. Fukuda K, Shoda T, Morikawa H, Kato S, Mima H, Mori K (1998) Activation of phospholipase A2 by the nociceptin receptor expressed in Chinese hamster ovary cells. J Neurochem 71(5):2186–2192CrossRefGoogle Scholar
  28. Hawes BE, Fried S, Yao X, Weig B, Graziano MP (1998) Nociceptin (ORL-1) and mu-opioid receptors mediate mitogen-activated protein kinase activation in CHO cells through a Gi-coupled signaling pathway: evidence for distinct mechanisms of agonist-mediated desensitization. J Neurochem 71(3):1024–1033CrossRefGoogle Scholar
  29. Lou LG, Zhang Z, Ma L, Pei G (1998) Nociceptin/Orphanin FQ activates mitogen-activated protein kinase in Chinese hamster ovary cells expressing opioid receptor-like receptor. J Neurochem 70(3):1316–1322CrossRefGoogle Scholar
  30. Malfacini D, Ambrosio C, Sbraccia M, Trapella C, Guerrini R, Bonora M et al (2015) Pharmacological profile of nociceptin/orphanin FQ receptors interacting with G-proteins and β-arrestins 2. PLoS One 10(8):e0132865CrossRefGoogle Scholar
  31. Melief EJ, Miyatake M, Bruchas MR, Chavkin C (2010) Ligand-directed c-Jun N-terminal kinase activation disrupts opioid receptor signaling. Proc Natl Acad Sci 107(25):11608–11613CrossRefGoogle Scholar
  32. Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P et al (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377(6549):532CrossRefGoogle Scholar
  33. Mittal N, Roberts K, Pal K, Bentolila LA, Fultz E, Minasyan A et al (2013) Select G-protein-coupled receptors modulate agonist-induced signaling via a ROCK, LIMK, and β-arrestin 1 pathway. Cell Rep 5(4):1010–1021CrossRefGoogle Scholar
  34. Narita M, Mizoguchi H, Oji DE, Narita M, Dun NJ, Hwang BH et al (1999) Identification of the G-protein-coupled ORL1 receptor in the mouse spinal cord by [35S]-GTPγS binding and immunohistochemistry. Br J Pharmacol 128(6):1300–1306CrossRefGoogle Scholar
  35. Raman M, Chen W, Cobb MH (2007) Differential regulation and properties of MAPKs. Oncogene 26(22):3100CrossRefGoogle Scholar
  36. Rizzi A, Cerlesi MC, Ruzza C, Malfacini D, Ferrari F, Bianco S et al (2016) Pharmacological characterization of cebranopadol a novel analgesic acting as mixed nociceptin/orphanin FQ and opioid receptor agonist. Pharmacol Res Perspect 4(4):e00247CrossRefGoogle Scholar
  37. Ruiz-Velasco V, Puhl HL, Fuller BC, Sumner AD (2005) Modulation of Ca2+ channels by opioid receptor-like 1 receptors natively expressed in rat stellate ganglion neurons innervating cardiac muscle. J Pharmacol Exp Ther 314(3):987–994CrossRefGoogle Scholar
  38. Sim LJ, Xiao R, Childers SR (1996) Identification of opioid receptor-like (ORL1) peptide-stimulated [35S] GTP gamma S binding in rat brain. Neuroreport 7(3):729–733CrossRefGoogle Scholar
  39. Spampinato S, di Toro R, Qasem AR (2001) Nociceptin-induced internalization of the ORL1 receptor in human neuroblastoma cells. Neuroreport 12(14):3159–3163CrossRefGoogle Scholar
  40. Spampinato S, di Toro R, Alessandri M, Murari G (2002) Agonist-induced internalization and desensitization of the human nociceptin receptor expressed in CHO cells. Cell Mol Life Sci 59(12):2172–2183CrossRefGoogle Scholar
  41. Spampinato S, Baiula M, Calienni M (2007) Agonist-regulated internalization and desensitization of the human nociceptin receptor expressed in CHO cells. Curr Drug Targets 8(1):137–146CrossRefGoogle Scholar
  42. Toll L, Bruchas MR, Cox BM, Zaveri NT (2016) Nociceptin/orphanin FQ receptor structure, signaling, ligands, functions, and interactions with opioid systems. Pharmacol Rev 68(2):419–457CrossRefGoogle Scholar
  43. Whalen EJ, Rajagopal S, Lefkowitz RJ (2011) Therapeutic potential of β-arrestin-and G protein-biased agonists. Trends Mol Med 17(3):126–139CrossRefGoogle Scholar
  44. Wickman K, Clapham DE (1995) Ion channel regulation by G proteins. Physiol Rev 75(4):865–885CrossRefGoogle Scholar
  45. Yeon KY, Sim MY, Choi SY, Lee SJ, Park K, Kim JS et al (2004) Molecular mechanisms underlying calcium current modulation by nociceptin. Neuroreport 15(14):2205–2209CrossRefGoogle Scholar
  46. Yung LY, Joshi SA, Chan RY, Chan JS, Pei G, Wong YH (1999) GαL1 (Gα14) couples the opioid receptor-like1 receptor to stimulation of phospholipase C. J Pharmacol Exp Ther 288(1):232–238PubMedGoogle Scholar
  47. Zamponi GW, Snutch TP (1998) Modulation of voltage-dependent calcium channels by G proteins. Curr Opin Neurobiol 8(3):351–356CrossRefGoogle Scholar
  48. Zamponi GW, Snutch TP (2002) Modulating modulation: crosstalk between regulatory pathways of presynaptic calcium channels. Mol Interv 2(8):476CrossRefGoogle Scholar
  49. Zhang Z, Xin SM, Wu GX, Zhang WB, Ma L, Pei G (1999) Endogenous δ-opioid and ORL1 receptors couple to phosphorylation and activation of p38 MAPK in NG108-15 cells and this is regulated by protein kinase A and protein kinase C. J Neurochem 73(4):1502–1509CrossRefGoogle Scholar
  50. Zhang NR, Planer W, Siuda ER, Zhao H-C, Stickler L, Chang SD, Baird MA, Cao Y-Q, Bruchas MR (2012) Serine 363 is required for nociceptin/orphanin FQ opioid receptor (NOPR) desensitization, internalization, and arrestin signaling. J Biol Chem 287:42019–42030CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Anesthesiology, Division of Basic ResearchWashington University School of MedicineSt. LouisUSA
  2. 2.Department of Anesthesiology and Pain Medicine, Center for Neurobiology of Addiction, Pain, and EmotionUniversity of WashingtonSeattleUSA

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