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

Protease-activated receptor 2 (PAR 2 ) 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 PAR 2 activation on single TRPV1 channel activities in isolated pulmonary sensory neurons. Our immunohistochemical study demonstrated the expression of PAR 2 in rat vagal pulmonary sensory neurons. Our patch-clamp study further showed that intracellular application of capsaicin (0.75 μ m ) 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 PAR 2 -activating peptide (100 μ m , 2 min). Pretreatment with trypsin (0.1 μ m , 2 min) also increased the single-channel P o , and the effect was completely inhibited by soybean trypsin inhibitor (0.5 μ m , 3 min). In addition, the effect of PAR 2 activation was abolished by either U73122 (1 μ m , 4 min), a phospholipase C inhibitor, or chelerythrine (10 μ m , 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.