{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:11:04Z","timestamp":1785305464813,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T00:00:00Z","timestamp":1550707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1HL137807"],"award-info":[{"award-number":["RO1HL137807"]}],"id":[{"id":"10.13039\/100000002","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":[[2019,4]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Sphingosine\u20101\u2010phosphate (S1P) strongly activates mouse vagal C\u2010fibres in the airways.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Airway\u2010specific nodose and jugular C\u2010fibre neurons express mRNA coding for the S1P receptor S1PR3.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>S1P activation of nodose C\u2010fibres is inhibited by a S1PR3 antagonist.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>S1P activation of nodose C\u2010fibres does not occur in S1PR3 knockout mice.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>We evaluated the effect of sphingosine\u20101\u2010phosphate (S1P), a lipid that is elevated during airway inflammatory conditions like asthma, for its ability to stimulate vagal afferent C\u2010fibres in mouse lungs. Single cell RT\u2010PCR on lung\u2010specific vagal afferent neurons revealed that both TRPV1\u2010expressing and TRPV1\u2010non\u2010expressing nodose neurons express mRNA coding for the S1P receptor S1PR3. TRPV1\u2010expressing airway\u2010specific jugular ganglion neurons also express S1PR3 mRNA. S1PR1 and S1PR2 mRNAs were also found to be expressed but only in a limited subset (32% and 22%, respectively) of airway\u2010specific vagal sensory neurons; whereas S1PR4 and S1PR5 were rarely expressed. We used large scale two\u2010photon imaging of the nodose ganglia from our <jats:italic>ex vivo<\/jats:italic> preparation isolated from <jats:italic>Pirt\u2010Cre;R26\u2010GCaMP6s<\/jats:italic> transgenic mice, which allows for simultaneous monitoring of calcium transients in \u223c1000 neuronal cell bodies in the ganglia during tracheal perfusion with S1P (10\u00a0\u03bcM). We found that S1P in the lungs strongly activated 81.5% of nodose fibres, 70% of which were also activated by capsaicin. Single fibre electrophysiological recordings confirmed that S1P evoked action potential (AP) generation in a concentration\u2010dependent manner (0.1\u201310\u00a0\u03bcM). Action potential generation by S1P in nodose C\u2010fibres was effectively inhibited by the S1PR3 antagonist TY 52156 (10\u00a0\u03bcM). Finally, in S1PR3 knockout mice, S1P was not able to activate any of the airway nodose C\u2010fibres analysed. These results support the hypothesis that S1P may play a role in evoking C\u2010fibre\u2010mediated airway sensations and reflexes that are associated with airway inflammatory diseases.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277521","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T03:58:17Z","timestamp":1550807897000},"page":"2007-2019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Sphingosine\u20101\u2010phosphate activates mouse vagal airway afferent C\u2010fibres via S1PR3 receptors"],"prefix":"10.1113","volume":"597","author":[{"given":"Mayur J.","family":"Patil","sequence":"first","affiliation":[{"name":"Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya","family":"Meeker","sequence":"additional","affiliation":[{"name":"Department of Medicine Johns Hopkins 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