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Published ahead of print on May 15, 2009, doi:10.1165/rcmb.2008-0488OC
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Submitted on December 16, 2008
Accepted on May 15, 2009

Nociceptin Modulates Bronchoconstriction Induced by Sensory Nerve Activation in Mouse Lung

Bruno D'Agostino1*, Donatella Orlotti1, Girolamo Calò2, Nikol Sullo1, Mariangela Russo1, Remo Guerrini3, Marilisa De Nardo1, Filomena Mazzeo4, Sanzio Candeletti5, and Francesco Rossi6

1 Department of Experimental Medicine-Section of Pharmacology, Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy, 2 Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Center, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy, 3 Department of Pharmaceutical Sciences and Biotechnology Centre, University of Ferrara, Ferrara, Italy, 4 Faculty of Movement Sciences (DiSiST), University Parthenope of Naples, Naples, Italy, 5 Department of Pharmacology, University of Bologna, Bologna, Italy, 6 Department of Experimental Medicine-Section of Pharmacology, Second University of Naples, Naples, Italy

* To whom correspondence should be addressed. E-mail: bruno.dagostino{at}unina2.it.

Background: Nociceptin/orphanin FQ (N/OFQ) the endogenous ligand for the N/OFQ peptide receptor (NOP) inhibits tachykinin release in the airway of several animal models. The aim of this study was to investigate the role of N/OFQ-NOP receptor system in bronchoconstriction induced by sensory nerve activation in the isolated mouse lung. Materials and Methods: We used C57BL/6J NOP+/+, NOP-/- and Balb/C mice sensitised or not to ovalbumin. Bronchopulmonary function coupled with measurements of endogenous N/OFQ levels before and after capsaicin induced bronchoconstriction in presence or in absence of NOP selective agonists/ antagonists are presented. Results: N/OFQ significantly inhibited capsaicin induced bronchoconstriction in both naive and sensitized mice, these latter animals displaying airway hyperresponsiveness to capsaicin. The inhibitory effect of N/OFQ were not observed in NOP-/- mice and were mimicked/abolished by the selective NOP agonist/antagonist UFP-112/UFP-101 in NOP+/+ mice. UFP-101, alone potentiated the effect of capsaicin in naive but not in sensitized mice. Endogenous N/OFQ levels significantly decreased in sensitized with respect to naive mice. Conclusions: We have demonstrated that a reduction in endogenous N/OFQ or the lack of its receptor causes an increase in capsaicin induced bronchoconstriction implying a role for the N/OFQ-NOP receptor system in the modulation of capsaicin effects. Moreover, for the first time we documented differential airway responsiveness to capsaicin between naive and sensitized mice due, at least in part, to decreased endogenous N/OFQ levels in sensitized mice.


Key words: Endogenous N/OFQ • airway responsiveness • allergic asthma • sensory nerves • NOP receptor






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