title: The effects of nociceptin peptide (N/OFQ)-receptor (NOP) system activation in the airways.
abstract: The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide (NOP) receptor. It is cleaved from a larger precursor identified as prepronociceptin (ppN/OFQ). NOP is a member of the seven transmembrane-spanning G-protein coupled receptor (GPCR) family. ppN/OFQ and NOP receptors are widely distributed in different human tissues. Asthma is a complex heterogeneous disease characterized by variable airflow obstruction, bronchial hyper-responsiveness and chronic airway inflammation. Limited therapeutic effectiveness of currently available asthma therapies warrants identification of new drug compounds. Evidence from animal studies suggests that N/OFQ modulates airway contraction and inflammation. Interestingly up regulation of the N/OFQ-NOP system reduces airway hyper-responsiveness. In contrast, inflammatory cells central to the inflammatory response in asthma may be both sources of N/OFQ and respond to NOP activation. Hence paradoxical dysregulation of the N/OFQ-NOP system may potentially play an important role in regulating airway inflammation and airway tone. To date there is no data on N/OFQ-NOP expression in the human airways. Therefore, the potential role of N/OFQ-NOP system in asthma is unknown. This review focuses on its physiological effects within airways and potential value as a novel asthma therapy.
authors.affiliation: Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group), Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Leicester Royal Infirmary, Leicester, UK. ss616@le.ac.uk
authors.forename: Shailendra R
authors.initials: SR
authors.lastname: Singh
authors.forename: Nikol
authors.initials: N
authors.lastname: Sullo
authors.forename: Bruno
authors.initials: B
authors.lastname: D'Agostino
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.forename: David G
authors.initials: DG
authors.lastname: Lambert
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D003371:Cough / Q000276:immunology / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D018847:Opioid Peptides / Q000502:physiology*; D011957:Receptors, Opioid / Q000378:metabolism*; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D018927:Anti-Asthmatic Agents; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human