Inhibition of low pH evoked activation of airway sensory nerves by capsazepine, a novel capsaicin-receptor antagonist.
Low pH is a well known sensory irritant in pathological conditions such as inflammation. The mechanisms underlying this low pH effect were therefore studied in the guinea pig. Acid exposure caused marked nasal irritation via a specific subset of sensory nerves sensitive to capsaicin. Furthermore, acid caused bronchoconstriction via release of neuropeptides from capsaicin sensitive afferents. Interestingly, capsazepine, a recently developed competitive capsaicin receptor antagonist, selectively inhibited these responses to low pH. Ruthenium red, which blocks the cation channel associated with the capsaicin receptor, had effects similar to those of capsazepine. Therefore, acid irritation of the airway mucosa may involve capsaicin-receptor mechanisms and capsazepine represents a novel protective agent.
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D004558:Electric Stimulation; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D015288:Neurokinin A / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects; D012430:Ruthenium Red / Q000494:pharmacology; D013990:Tidal Volume / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology*
D002951:Citrates; D011955:Receptors, Drug; D012430:Ruthenium Red; D019343:Citric Acid; D009538:Nicotine; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin