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Institutes of 1Physiology, School of Medicine, National Yang-Ming UniversityInstitutes of 3Pharmacology, School of Medicine, National Yang-Ming University
2 Department of Physiology, Taipei Medical University, Taipei, Taiwan
The mechanisms of sensory transduction of pulmonary reactive oxygen species (ROS) by capsaicin-sensitive vagal lung afferent fibres are unclear. To investigate the role of transient receptor potential vanilloid 1 (TRPV1) receptors and P2X purinoceptors in this sensory transduction, we recorded fibre activity (FA) from 132 fibres of this type in 132 anaesthetized and ventilated rats. Airway challenge of aerosolized H2O2 (0, 0.2 and 0.4%) produced a concentration-dependant fibre stimulation. The fibre responses to 0.4% H2O2 were attenuated by dimethylthiourea (a hydroxyl radical (·OH) scavenger; change in fibre activity (
FA), –55 ± 9%) or deferoxamine (an iron-chelator that prevents formation of ·OH; FA, –59 ± 9%), were prevented by catalase (an enzyme catalysing H2O2; FA, –96 ± 3%) and were unaffected by the vehicle for dimethylthiourea, iron-saturated deferoxamine or heat-inactivated catalase. The fibre responses to 0.4% H2O2 were attenuated by capsazepine (a TRPV1 receptor antagonist; FA, –39 ± 9%) or iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS, a P2X receptor antagonist; FA, –51 ± 9%), were further reduced by capsazepine and iso-PPADS in combination (FA, –70 ± 13%), and were unaltered by their vehicles. The fibre responses to cigarette smoke (20 ml), an irritant that generates ROS, were attenuated by dimethylthiourea (FA, –61 ± 9%) or capsazepine and iso-PPADS in combination (FA, –67 ± 9%). These results suggest that both the TRPV1 and P2X receptors mediate the sensory transduction of ROS, especially H2O2 and ·OH, by capsaicin-sensitive vagal lung afferent fibres.
(Received 4 March 2005;
accepted after revision 24 March 2005;
first published online 31 March 2005)
Corresponding author Y. R. Kou: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. Email: yrkou{at}ym.edu.tw
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