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 TRPV1channel 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 microM) induced single channel current that exhibited outward rectification in these neurons. The probability of the channel being open (Po) was significantly increased after the cells were pretreated with PAR2-activating peptide (100 microM, 2 min). Pretreatment with trypsin (0.1 microM, 2 min) also increased the single-channel Po, and the effect was completely inhibited by soybean trypsin inhibitor (0.5 microM, 3 min). In addition, the effect of PAR2 activation was abolished by either U73122 (1 microM, 4 min),a phospholipase C inhibitor, or chelerythrine (10 microM, 4 min), a protein kinase C inhibitor. In conclusion, our data demonstrated that activation of PAR2 upregulated single-channel activitiesofTRPV1and that the effect was mediated through the protein kinase C-dependent transduction pathway.
Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. qgu2@email.uky.edu
Qihai
Q
Gu
Lu-Yuan
LY
Lee
D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D008168:Lung / Q000294:innervation; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology*; D014357:Trypsin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014630:Vagus Nerve / Q000502:physiology
D053119:Benzophenanthridines; D004963:Estrenes; D011760:Pyrrolidinones; D044464:Receptor, PAR-2; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C016299:chelerythrine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D014357:Trypsin