{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:03:07Z","timestamp":1791291787815,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2008,7,14]],"date-time":"2008-07-14T00:00:00Z","timestamp":1215993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2008,7,15]]},"abstract":"<jats:p>Transient receptor potential (TRP) A1 channels are cation channels found preferentially on nociceptive sensory neurones, including capsaicin\u2010sensitive TRPV1\u2010expressing vagal bronchopulmonary C\u2010fibres, and are activated by electrophilic compounds such as mustard oil and cinnamaldehyde. Oxidative stress, a pathological feature of many respiratory diseases, causes the endogenous formation of a number of reactive electrophilic alkenals via lipid peroxidation. One such alkenal, 4\u2010hydroxynonenal (4HNE), activates TRPA1 in cultured sensory neurones. However, our data demonstrate that 100 \u03bc<jats:sc>m<\/jats:sc> 4HNE was unable to evoke significant action potential discharge or tachykinin release from bronchopulmonary C\u2010fibre terminals. Instead, another endogenously produced alkenal, 4\u2010oxononenal (4ONE, 10 \u03bc<jats:sc>m<\/jats:sc>), which is far more electrophilic than 4HNE, caused substantial action potential discharge and tachykinin release from bronchopulmonary C\u2010fibre terminals. The activation of mouse bronchopulmonary C\u2010fibre terminals by 4ONE (10\u2013100 \u03bc<jats:sc>m<\/jats:sc>) was mediated entirely by TRPA1 channels, based on the absence of responses in C\u2010fibre terminals from TRPA1 knockout mice. Interestingly, although the robust increases in calcium caused by 4ONE (0.1\u201310 \u03bc<jats:sc>m<\/jats:sc>) in dissociated vagal neurones were essentially abolished in TRPA1 knockout mice, at 100 \u03bc<jats:sc>m<\/jats:sc> 4ONE caused a large TRPV1\u2010dependent response. Furthermore, 4ONE (100 \u03bc<jats:sc>m<\/jats:sc>) was shown to activate TRPV1 channel\u2010expressing HEK cells. In conclusion, the data support the hypothesis that 4\u2010ONE is a relevant endogenous activator of vagal C\u2010fibres via an interaction with TRPA1, and at less relevant concentrations, it may activate nerves via TRPV1.<\/jats:p>","DOI":"10.1113\/jphysiol.2008.153585","type":"journal-article","created":{"date-parts":[[2008,5,23]],"date-time":"2008-05-23T00:44:25Z","timestamp":1211503465000},"page":"3447-3459","source":"Crossref","is-referenced-by-count":198,"title":["Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C\u2010fibres by the endogenous autacoid 4\u2010oxononenal"],"prefix":"10.1113","volume":"586","author":[{"given":"T. E.","family":"Taylor\u2010Clark","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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