{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T14:44:18Z","timestamp":1781275458671,"version":"3.54.1"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T00:00:00Z","timestamp":1581638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["107\u20102320\u2010B\u2010038\u2010041"],"award-info":[{"award-number":["107\u20102320\u2010B\u2010038\u2010041"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["107\u20102320\u2010B\u2010038\u2010049\u2010MY3"],"award-info":[{"award-number":["107\u20102320\u2010B\u2010038\u2010049\u2010MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Brief inhalation of SO<jats:sub>2<\/jats:sub> of concentration &gt;500\u00a0p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C\u2010fibres in anaesthetized rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This stimulatory effect was drastically diminished by a pretreatment with NaHCO<jats:sub>3<\/jats:sub> that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and\/or tissue generated by inhaled SO<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The stimulation was completely abolished by pretreatment with antagonists of both acid\u2010sensing ion channels and transient receptor potential vanilloid type\u20101 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO<jats:sub>2<\/jats:sub> inhalation challenge in awake mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Inhalation of sulfur dioxide (SO<jats:sub>2<\/jats:sub>) triggers coughs and reflex bronchoconstriction, and stimulation of vagal bronchopulmonary C\u2010fibres is primarily responsible. However, the mechanism underlying this stimulatory effect is not yet fully understood. In this study, we tested the hypothesis that the C\u2010fibre stimulation was caused by SO<jats:sub>2<\/jats:sub>\u2010induced local tissue acidosis in the lung and airways. Single\u2010unit activities of bronchopulmonary C\u2010fibres in response to inhalation challenges of SO<jats:sub>2<\/jats:sub> (500\u20131500\u00a0p.p.m., 10 breaths) were measured in anaesthetized rats. Inhalation of SO<jats:sub>2<\/jats:sub> reproducibly induced a pronounced and sustained stimulation (lasting for 15\u201360\u00a0s) of pulmonary C\u2010fibres in a concentration\u2010dependent manner. This stimulatory effect was significantly attenuated by an increase in arterial pH generated by infusion of sodium bicarbonate (NaHCO<jats:sub>3<\/jats:sub>), and completely abrogated by a combined pretreatment with amiloride (an antagonist of acid\u2010sensing ion channels, ASICs) and AMG8910 (a selective antagonist of the transient receptor potential vanilloid type\u20101 receptor, TRPV1). Furthermore, in isolated rat vagal pulmonary sensory neurones, perfusion of an aqueous solution of SO<jats:sub>2<\/jats:sub> evoked a transient increase in the intracellular Ca<jats:sup>2+<\/jats:sup> concentration; this response was also markedly diminished by a pretreatment with amiloride and AMG8910. In addition, inhalation of SO<jats:sub>2<\/jats:sub> consistently evoked coughs in awake mice; responses were significantly smaller in TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup> mice than in wild\u2010type mice, and almost completely abolished after a pretreatment with amiloride in TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup> mice. These results suggested that the stimulatory effect of inhaled SO<jats:sub>2<\/jats:sub> on bronchopulmonary C\u2010fibres was generated by acidification of fluid and\/or tissue in the lung and airways, which activated both ASICs and TRPV1 expressed in these sensory nerves.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp279152","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T11:54:53Z","timestamp":1577793293000},"page":"1093-1108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C\u2010fibres"],"prefix":"10.1113","volume":"598","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-2222","authenticated-orcid":false,"given":"An\u2010Hsuan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Physiology University of Kentucky Medical Centre  Lexington KY 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