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

Respir Physiol Neurobiol. 2013 Oct 1;189(1):1-9. doi: 10.1016/j.resp.2013.06.021. Epub 2013 Jul 5.

Abstract

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.

Keywords: ATP; Cyclooxygenase metabolites; P2X receptors; TRPA1 receptors; TRPV1 receptors; Vagal lung C-fibers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Enzyme-Linked Immunosorbent Assay
  • Lung / innervation
  • Lung / metabolism*
  • Male
  • Mechanotransduction, Cellular / physiology*
  • Nerve Fibers, Unmyelinated / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Receptors, Purinergic P2X / metabolism*
  • TRPA1 Cation Channel
  • TRPC Cation Channels / metabolism*
  • TRPV Cation Channels / metabolism*
  • Vagus Nerve / metabolism

Substances

  • Reactive Oxygen Species
  • Receptors, Purinergic P2X
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TRPV Cation Channels
  • Trpa1 protein, rat
  • Trpv1 protein, rat
  • Adenosine Triphosphate
  • Prostaglandin-Endoperoxide Synthases