Sensory transduction of pulmonary reactive oxygen species by capsaicin-sensitive vagal lung afferent fibres in rats.
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 (DeltaFA), -55+/-9%) or deferoxamine (an iron-chelator that prevents formation of .OH; DeltaFA, -59+/-9%), were prevented by catalase (an enzyme catalysing H2O2; DeltaFA, -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; DeltaFA, -39+/-9%) or iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS, a P2X receptor antagonist; DeltaFA, -51+/-9%), were further reduced by capsazepine and iso-PPADS in combination (DeltaFA, -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 (DeltaFA, -61+/-9%) or capsazepine and iso-PPADS in combination (DeltaFA, -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.
Ruan
Ting
T
Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Lin
You Shuei
YS
Lin
Kae-Shin
KS
Kou
Yu Ru
YR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007473:Ion Channels / Q000502:physiology; D008168:Lung / Q000294:innervation* / Q000378:metabolism*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000502:physiology; D012907:Smoking; D013268:Stimulation, Chemical; D050916:TRPV Cation Channels; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; D016877:Oxidants; D017382:Reactive Oxygen Species; D018048:Receptors, Purinergic P2; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D006861:Hydrogen Peroxide; D002211:Capsaicin