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Role of ATP in the ROS-mediated laryngeal airway hyperreactivity induced by laryngeal acid-pepsin insult in anesthetized rats

Institutes of 1 Clinical Medicine, 2 Physiology, and 3 Emergency and Critical Care Medicine and 4 Department of Otorhinolaryngology, School of Medicine, National Yang-Ming University, Taipei; and 5 Department of Otolaryngology, Taipei Veteran General Hospital, Taipei, Taiwan Submitted 20 November 20...

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Published in:Journal of applied physiology (1985) 2009-05, Vol.106 (5), p.1584-1592
Main Authors: Tsai, Tung-Lung, Chang, Shyue-Yih, Ho, Ching-Yin, Kou, Yu Ru
Format: Article
Language:English
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Summary:Institutes of 1 Clinical Medicine, 2 Physiology, and 3 Emergency and Critical Care Medicine and 4 Department of Otorhinolaryngology, School of Medicine, National Yang-Ming University, Taipei; and 5 Department of Otolaryngology, Taipei Veteran General Hospital, Taipei, Taiwan Submitted 20 November 2008 ; accepted in final form 18 February 2009 The pathogenetic mechanisms of laryngeal airway hyperreactivity (LAH) in patients with extraesophageal reflux are unclear. We recently reported that a laryngeal acid-pepsin insult produces LAH that is mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by reactive oxygen species (ROS) in rats. Since ROS may promote the release of ATP from cells, we hypothesized that activation of P2X purinoceptors by ATP subsequent to an increase in ROS induces LAH in an inflamed larynx that has been insulted by acid-pepsin or H 2 O 2 (a major type of ROS). The larynxes of 208 anesthetized rats were functionally isolated while the animals breathed spontaneously. Ammonia vapor was delivered into the larynx to measure laryngeal reflex reactivity. Laryngeal insult with acid-pepsin or H 2 O 2 produced LAH with similar characteristics. The H 2 O 2 -induced LAH was prevented by laryngeal pretreatment with dimethylthiourea (a hydroxyl radical scavenger), suggesting a critical role for ROS. The LAH induced by both insults were completely prevented by ATP scavengers (a combination of apyrase and adenosine deaminase) or a P2X receptor antagonist ( iso -pyridoxalphosphate-6-azophenyl-2',5'-disulfonate). Laryngeal application of a P2X receptor agonist ( ,β-methylene-ATP) also produced LAH. An insult with either acid-pepsin or H 2 O 2 similarly promoted an increase in the levels of ATP, lipid peroxidation, and inflammation in the larynx. Our findings suggest that laryngeal insult with acid-pepsin or H 2 O 2 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 LAH. extraesophageal reflux; laryngeal capsaicin-sensitive afferent fibers; adenosine 5'-triphosphate; reactive oxygen species Address for reprint requests and other correspondence: Y. R. Kou, Institute of Physiology, School of Medicine, National Yang-Ming Univ., Taipei 11221, Taiwan (e-mail: yrkou{at}ym.edu.tw )
ISSN:8750-7587
1522-1601
DOI:10.1152/japplphysiol.91517.2008