Advertisement

N/OFQ-NOP System and Airways

  • Bruno D’AgostinoEmail author
  • Manuela Sgambato
  • Renata Esposito
  • Giuseppe Spaziano
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 254)

Abstract

Asthma is a heterogeneous chronic inflammatory disease of the airways. The most prevalent form is atopic asthma, which is initiated by the exposure to (inhaled) allergens. Intermittent attacks of breathlessness, airways hyperresponsiveness, wheezing, coughing, and resultant allergen-specific immune responses characterize the disease. Nociceptin/OFQ-NOP receptor system is able to combine anti-hyperresponsiveness and immunomodulatory actions. In particular, N/OFQ is able to inhibit airways microvascular leakage and bronchoconstriction through a presynaptic and non-opioid mechanism of action that blocks tachykinin release. Moreover, it also acts on allergenic sensitization because it is able to modulate the immune response that triggers the development of airway hyperresponsiveness through an interaction on cell membranes of dendritic cells (DCs) that are generally responsible to start and sustain allergic T helper 2 (TH2)-cell responses to inhaled allergens in asthma. In asthmatic patients, sputum showed elevated N/OFQ levels that are related to increased eosinophil counts. The addition of exogenous N/OFQ in sputum obtained from patients with severe asthma attenuated eosinophils migration and release of inflammatory mediators. These observations confirmed that elevated endogenous N/OFQ levels in asthmatic sputum were lower than the ones required to exert beneficial effects, suggesting that supplementation with exogenous N/OFQ may need. In conclusion, the innovative role of N/OFQ in counteracting airways inflammation/hyperresponsiveness opens new potential targets/strategies in asthma treatment.

Keywords

Airway Airway hyperresponsiveness Asthma Cough Nociceptin 

References

  1. Basso M, Risse PA, Naline E, Calo G, Guerrini R, Regoli D, Advenier C (2005) Nociceptin/orphanin FQ inhibits electrically induced contractions of the human bronchus via NOP receptor activation. Peptides 26(8):1492–1496CrossRefGoogle Scholar
  2. Bolser DC, McLeod RL, Tulshian DB, Hey JA (2001) Antitussive action of nociceptin in the cat. Eur J Pharmacol 430(1):107–111CrossRefGoogle Scholar
  3. Brightling CE, Gupta S, Gonem S, Siddiqui S (2012) Lung damage and airway remodelling in severe asthma. Clin Exp Allergy 425:638–649CrossRefGoogle Scholar
  4. D’Agostino B, Advenier C, de Palma R, Gallelli L, Marrocco G, Abbate GF, Rossi F (2002) The involvement of sensory neuropeptides in airway hyper-responsiveness in rabbits sensitized and challenged to Parietaria judaica. Clin Exp Allergy 32(3):472–479CrossRefGoogle Scholar
  5. D’Agostino B, Marrocco G, De Nardo M, Calò G, Guerrini R, Gallelli L, Advenier C, Rossi F (2005) Activation of the nociceptin/orphanin FQ receptor reduces bronchoconstriction and microvascular leakage in a rabbit model of gastroesophageal reflux. Br J Pharmacol 144(6):813–820CrossRefGoogle Scholar
  6. D’Agostino B, Orlotti D, Calò G, Sullo N, Russo M, Guerrini R, De Nardo M, Mazzeo F, Candeletti S, Rossi F (2010) Nociceptin modulates bronchoconstriction induced by sensory nerve activation in mouse lung. Am J Respir Cell Mol Biol 42(2):250–254CrossRefGoogle Scholar
  7. Filosa R, Peduto A, Schaible AM, Krauth V, Weinigel C, Barz D, Petronzi C, Bruno F, Roviezzo F, Spaziano G, D’Agostino B, De Rosa M, Werz O (2015) Novel series of benzoquinones with high potency against 5-lipoxygenase in human polymorphonuclear leukocytes. Eur J Med Chem 94:132–139CrossRefGoogle Scholar
  8. Fischer A, Forssmann WG, Undem BJ (1998) Nociceptin-induced inhibition of tachykinergic neurotransmission in guinea pig bronchus. J Pharmacol Exp Ther 285(2):902–907PubMedGoogle Scholar
  9. Gallelli L, D’Agostino B, Marrocco G, De Rosa G, Filippelli W, Rossi F, Advenier C (2003) Role of tachykinins in the bronchoconstriction induced by HCl intraesophageal instillation in the rabbit. Life Sci 72(10):1135–1142CrossRefGoogle Scholar
  10. Galli SJ, Tsai M, Piliponsky AM (2008) The development of allergic inflammation. Nature 454(7203):445–454. ReviewCrossRefGoogle Scholar
  11. Holgate ST (2007) Epithelium dysfunction in asthma. J Allergy Clin Immunol 120:1233–1244CrossRefGoogle Scholar
  12. Jia Y, Wang X, Aponte SI, Rivelli MA, Yang R, Rizzo CA, Corboz MR, Priestley T, Hey JA (2002) Nociceptin/orphanin FQ inhibits capsaicin-induced guinea-pig airway contraction through an inward-rectifier potassium channel. Br J Pharmacol 135(3):764–770CrossRefGoogle Scholar
  13. Lambert DG (2008) The nociceptin/orphanin FQ receptor: a target with broad therapeutic potential. Nat Rev Drug Discov 7:694–710CrossRefGoogle Scholar
  14. Lazzeri M, Calò G, Spinelli M, Guerrini R, Salvadori S, Beneforti P et al (2003) Urodynamic effects of intravesical nociceptin/orphanin FQ in neurogenic detrusor overactivity: a randomized, placebo-controlled, double-blind study. Urology 61:946–950CrossRefGoogle Scholar
  15. Lee MG, Undem BJ, Brown C, Carr MJ (2006) Effect of nociceptin in acid-evoked cough and airway sensory nerve activation in guinea pigs. Am J Respir Crit Care Med 173:271–275CrossRefGoogle Scholar
  16. McLeod RL, Parra LE, Mutter JC, Erickson CH, Carey GJ, Tulshian DB (2001) Nociceptin inhibits cough in the guinea-pig by activation of ORL(1) receptors. Br J Pharmacol 132(6):1175–1178CrossRefGoogle Scholar
  17. McLeod RL, Jia Y, Fernandez X, Parra LE, Wang X, Tulshian DB (2004) Antitussive profile of the NOP agonist Ro-64-6198 in the guinea pig. Pharmacology 71(3):143–149CrossRefGoogle Scholar
  18. Nigro E, Daniele A, Scudiero O, Ludovica Monaco M, Roviezzo F, D’Agostino B, Mazzarella G, Bianco A (2015) Adiponectin in asthma: implications for phenotyping. Curr Protein Pept Sci 16(3):182–187CrossRefGoogle Scholar
  19. Ray A, Cohn L (1999) Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. J Clin Invest 104:985–993CrossRefGoogle Scholar
  20. Rouget C, Cui YY, D’Agostino B, Faisy C, Naline E, Bardou M, Advenier C (2004) Nociceptin inhibits airway microvascular leakage induced by HCl intra-oesophageal instillation. Br J Pharmacol 141(6):1077–1083CrossRefGoogle Scholar
  21. Schröder W, Lambert DG, Ko MC, Koch T (2014) Functional plasticity of the N/OFQ-NOP receptor system determines analgesic properties of NOP receptor agonists. Br J Pharmacol 171:3777–3800CrossRefGoogle Scholar
  22. Shah S, Page CP, Spina D (1998) Nociceptin inhibits non-adrenergic non-cholinergic contraction in guinea-pig airway. Br J Pharmacol 125(3):510–516CrossRefGoogle Scholar
  23. Singh SR, Sullo N, D’Agostino B, Brightling CE, Lambert DG (2013) The effects of nociceptin peptide (N/OFQ)-receptor (NOP) system activation in the airways. Peptides 39:36–46CrossRefGoogle Scholar
  24. Singh SR, Sullo N, Matteis M, Spaziano G, McDonald J, Saunders R, Woodman L, Urbanek K, De Angelis A, De Palma R, Berair R, Pancholi M, Mistry V, Rossi F, Guerrini R, Calò G, D’Agostino B, Brightling CE, Lambert DG (2016) Nociceptin/orphanin FQ (N/OFQ) modulates immunopathology and airway hyperresponsiveness representing a novel target for the treatment of asthma. Br J Pharmacol 173(8):1286–1301CrossRefGoogle Scholar
  25. Spaziano G, Sorrentino R, Matteis M, Malgieri G, Sgambato M, Russo TP, Terlizzi M, Roviezzo F, Rossi F, Pinto A, Fattorusso R, D’Agostino B (2017) Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness. Clin Exp Allergy 47(2):208–216CrossRefGoogle Scholar
  26. Stretton D (1991) Non-adrenergic, non-cholinergic neural control of the airways. Clin Exp Pharmacol Physiol 18(10):675–684CrossRefGoogle Scholar
  27. Sullo N, Roviezzo F, Matteis M, Ianaro A, Calò G, Guerrini R, De Gruttola L, Spaziano G, Cirino G, Rossi F, D’Agostino B (2013) Nociceptin/orphanin FQ receptor activation decreases the airway hyperresponsiveness induced by allergen in sensitized mice. Am J Physiol Lung Cell Mol Physiol 304(10):L657–L664CrossRefGoogle Scholar
  28. Tartaglione G, Spaziano G, Sgambato M, Russo TP, Liparulo A, Esposito R, Mirra S, Filosa R, Roviezzo F, Polverino F, D’Agostino B (2018) Nociceptin/orphanin FQ in inflammation and remodelling of the small airways in experimental model of airway hyperresponsiveness. Physiol Rep 6(20):e13906CrossRefGoogle Scholar
  29. Urbanek K, De Angelis A, Spaziano G, Piegari E, Matteis M, Cappetta D, Esposito G, Russo R, Tartaglione G, De Palma R, Rossi F, D’Agostino B (2016) Intratracheal administration of mesenchymal stem cells modulates tachykinin system, suppresses airway remodeling and reduces airway hyperresponsiveness in an animal model. PLoS One 11(7):e0158746CrossRefGoogle Scholar
  30. Woodcock A, McLeod RL, Sadeh J, Smith JA (2010) The efficacy of a NOP1 agonist (SCH486757) in subacute cough. Lung 188(Suppl. 1):S47–S52CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bruno D’Agostino
    • 1
    Email author
  • Manuela Sgambato
    • 1
  • Renata Esposito
    • 1
  • Giuseppe Spaziano
    • 1
  1. 1.Department of Experimental Medicine, Section of Pharmacology L. DonatelliUniversity of Campania “L. Vanvitelli”NaplesItaly

Personalised recommendations