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The effects of nociceptin peptide (N/OFQ)–receptor (NOP) system activation in the airways

Author:
Singh, Shailendra R., Sullo, Nikol, D’Agostino, Bruno, Brightling, Christopher E., Lambert, David G.
Source:
Peptides 2013 v.39 pp. 36-46
ISSN:
0196-9781
Subject:
G-protein coupled receptors, air flow, asthma, drugs, humans, inflammation, therapeutics, tissues
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.
Agid:
1054651