title: Nociceptin modulates bronchoconstriction induced by sensory nerve activation in mouse lung.
abstract: 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 the N/OFQ-NOP receptor system in bronchoconstriction induced by sensory nerve activation in the isolated mouse lung. We used C57BL/6J NOP(+/+), NOP(-/-), and Balb/C mice sensitized (or not) to ovalbumin. Bronchopulmonary function coupled with measurements of endogenous N/OFQ levels before and after capsaicin-induced bronchoconstriction in the presence or absence of NOP-selective agonists/antagonists are presented. 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 University of Ferrara Peptide (UFP)-112/UFP-101 in NOP(+/+) mice. UFP-101 alone potentiated the effect of capsaicin in naive mice, but not in sensitized mice. Endogenous N/OFQ levels significantly decreased in sensitized mice relative to naive mice. 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 document differential airway responsiveness to capsaicin between naive and sensitized mice due, at least in part, to decreased endogenous N/OFQ levels in sensitized mice.
authors.affiliation: Department of Experimental Medicine, sect. of Pharmacology "L.Donatelli", Faculty of Medicine and Surgery, Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy. bruno.dagostino@unina2.it
authors.forename: Bruno
authors.initials: B
authors.lastname: D'Agostino
authors.forename: Donatella
authors.initials: D
authors.lastname: Orlotti
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calò
authors.forename: Nikol
authors.initials: N
authors.lastname: Sullo
authors.forename: Mariangela
authors.initials: M
authors.lastname: Russo
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Marilisa
authors.initials: M
authors.lastname: De Nardo
authors.forename: Filomena
authors.initials: F
authors.lastname: Mazzeo
authors.forename: Sanzio
authors.initials: S
authors.lastname: Candeletti
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology / Q000294:innervation* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018847:Opioid Peptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011957:Receptors, Opioid / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000485:Allergens; D002211:Capsaicin; D018847:Opioid Peptides; D010047:Ovalbumin; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722287:Oprl1 protein, mouse