Mediator mechanisms involved in TRPV1, TRPA1 and P2X receptor-mediated sensory transduction of pulmonary ROS by vagal lung C-fibers in rats

- Two mediators (cyclooxygenase metabolites and ATP) and three types of pharmacological receptors (the TRPV1, TRPA1 and P2X receptors) are involved in the sensory transduction of pulmonary ROS by vagal lung C-fibers.
- The functioning of the TRPV1 and TRPA1 in producing this sensory stimulation is at least in part mediated through the actions of cyclooxygenase metabolites.
- The functioning of P2X receptors is mediated through the action of ATP.

We investigated the mediator mechanisms involved in the sensory transduction of pulmonary reactive oxygen species (ROS) by vagal lung C-fibers in anesthetized rats. Airway challenge of aerosolized H2O2 (0.4%) stimulated these afferent fibers. The H2O2-induced responses were reduced by a cyclooxygenase inhibitor or ATP scavengers and also attenuated by an antagonist of TRPV1, TRPA1 or P2X receptors. The suppressive effect of the cyclooxygenase inhibitor was not affected by a combined treatment with the TRPV1 or TRPA1 antagonist, but was amplified by a combined treatment with the P2X antagonists. The suppressive effect of ATP scavengers was not affected by a combined treatment with the P2X antagonist, but was amplified by a combined treatment with the TRPV1 or TRPA1 antagonist. Thus, the actions of cyclooxygenase metabolites are mediated through the functioning of the TRPV1 and TRPA1 receptors, whereas the action of ATP is mediated through the functioning of P2X receptors.