Effect of protease-activated receptor 2 activation on single TRPV1 channel activities in rat vagal pulmonary sensory neurons

Protease-activated receptor 2 (PAR₂) is involved in airway inflammation and airway hyperresponsiveness; both are the prominent features of asthma. Transient receptor potential vanilloid receptor 1 (TRPV1) is expressed in pulmonary sensory nerves, functions as a thermal and chemical transducer and contributes to neurogenic inflammation. Using cell-attached single-channel recordings we investigated the effect of PAR₂ activation on single TRPV1 channel activities in isolated pulmonary sensory neurons. Our immunohistochemical study demonstrated the expression of PAR₂ in rat vagal pulmonary sensory neurons. Our patch-clamp study further showed that intracellular application of capsaicin (0.75 μm) induced single-channel current that exhibited outward rectification in these neurons. The probability of the channel being open (P_o) was significantly increased after the cells were pretreated with PAR₂-activating peptide (100 μm, 2 min). Pretreatment with trypsin (0.1 μm, 2 min) also increased the single-channel P_o, and the effect was completely inhibited by soybean trypsin inhibitor (0.5 μm, 3 min). In addition, the effect of PAR ₂ activation was abolished by either U73122 (1 μm, 4 min), a phospholipase C inhibitor, or chelerythrine (10 μm, 4 min), a protein kinase C inhibitor. In conclusion, our data demonstrated that activation of PAR ₂ upregulated single-channel activities of TRPV1 and that the effect was mediated through the protein kinase C-dependent transduction pathway.