title: Activation of P2X purinoceptors by ATP subsequent to an increase in reactive oxygen species causes enhanced laryngeal reflex reactivity in a rat model of extraoesophageal reflux.
abstract: BACKGROUND
  The pathogenetic mechanisms of enhanced laryngeal reflex reactivity (ELRR) in patients with extraoesophageal reflux (EOR) are unclear. In a rat EOR model, a laryngeal acid-pepsin insult produces an ELRR that is mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by reactive oxygen species (ROS).
  
  
  OBJECTIVE
  We investigated whether activation of P2X receptors by ATP subsequent to an increase in ROS may induce ELRR in an inflamed larynx that has been insulted by acid-pepsin or H2O2.
  
  
  METHODS
  The larynxes of 184 anesthetized rats were functionally isolated while the animals breathed spontaneously. Ammonia vapor was delivered into the larynx to measure laryngeal reflex reactivity.
  
  
  RESULTS
  Laryngeal insult with acid-pepsin or H2O2 produced ELRR with similar characteristics. These two ELRR events were completely prevented by ATP scavengers (a combination of apyrase and adenosine deaminase) or a P2X receptor antagonist (iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate). Laryngeal application of a P2X receptor agonist (alpha,beta-methylene-ATP) also produced ELRR. An insult with either acid-pepsin or H2O2 similarly promoted an increase in the levels of ATP, lipid peroxidation and inflammation in the larynx.
  
  
  CONCLUSIONS
  Laryngeal insult with acid-pepsin or H2O2 induces inflammation and produces excess ROS in the rat's larynx. The latter may in turn promote the release of ATP to activate P2X receptors resulting in sensitization of capsaicin-sensitive laryngeal afferent fibers and ELRR.
authors.affiliation: School of Medicine, National Yang-Ming University, Taiwan.
authors.forename: Tung-Lung
authors.initials: TL
authors.lastname: Tsai
authors.forename: Shyue-Yih
authors.initials: SY
authors.lastname: Chang
authors.forename: Ching-Yin
authors.initials: CY
authors.lastname: Ho
authors.forename: Yu Ru
authors.initials: YR
authors.lastname: Kou