Published ahead of print on October 20, 2005, doi:10.1164/rccm.200507-1043OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200507-1043OC
Effect of Nociceptin in Acid-evoked Cough and Airway Sensory Nerve Activation in Guinea PigsJohns Hopkins Asthma and Allergy Center, Baltimore, Maryland; and UCB Research, Inc., Cambridge, Massachusetts Correspondence and requests for reprints should be addressed to Bradley J. Undem, Ph.D., Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: bundem{at}jhmi.edu Rationale: Nociceptin/orphanin FQ has been reported to inhibit capsaicin- and mechanically provoked cough in animal models, but the mechanism of this effect has not been elucidated. Objectives: The objectives of this study were to determine whether nociceptin inhibits acid-evoked cough in conscious animals and to evaluate the mechanism of this effect. Methods: We tested the effect of nociceptin on acid-induced cough in conscious guinea pigs and acid-induced nerve activation in airway-specific vagal sensory neurons using calcium imaging techniques and the gramicidin-perforated patch clamp technique.
Measurements and Main Results: Nociceptin (3 mg/kg, intraperitoneal) effectively inhibited acid-evoked cough in guinea pigs by nearly 70%. Acid (pH 5) increased intracellular free calcium in acutely dissociated vagal jugular ganglionic neurons. The acid-induced increase in intracellular calcium was inhibited by a selective transient receptor potential vanilloid-1 antagonist, 5-iodo-resiniferatoxin (1 µM, Conclusion: These results indicate that the inhibitory effect of nociceptin on acid-induced cough may result from a direct inhibitory effect on peripheral C-fiber activity caused by the selective inhibition of acid-induced transient receptor potential vanilloid-1 activation.
Key Words: acid • airway sensory • cough • nociceptin/orphanin FQ • transient receptor potential vanilloid-1 This article has been cited by other articles:
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80% reduction). The inhibitory effect of 5-iodo-resiniferatoxin on acid-induced increases in calcium was mimicked by nociceptin (0.1 µM). In gramicidin-perforated patch clamp recordings on airway-specific capsaicin-sensitive jugular ganglion neurons, acid (pH 5) induced two distinct inward currents. A transient current was evoked that was inhibited by amiloride and a sustained current was evoked that was inhibited by 5-iodo-resiniferatoxin. Nociceptin selectively inhibited only the sustained component of acid-induced inward current. 
