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Sphingosine\u20101\u2010phosphate (S1P) is a lipid with intracellular and extracellular functions. Extracellularly, it can act as an autacoid via interactions with S1P receptors. The present study aims to determine the effect of S1P on esophageal vagal afferent nerve functions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Extracellular single\u2010unit recordings were performed in ex vivo guinea pig esophageal\u2010vagal preparations. The action potentials (<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>s) evoked by mechanical distension and chemical perfusions applied to the vagal afferent nerve endings in the esophagus were recorded at their intact neuronal cell bodies in either nodose or jugular ganglia. The effects of S1P and its receptor subtype agonists on vagal afferents were recorded and compared. The expression of S1P receptors (S1<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>1\u20103) in esophageal\u2010labeled vagal nodose and jugular neurons was studied by single\u2010cell <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Sphingosine\u20101\u2010phosphate evoked <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> discharges in almost all esophageal jugular but not nodose C\u2010fibers without changing their responses to esophageal distension. Esophageal\u2010labeled vagal nodose and jugular neurons highly expressed transcripts of S1<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>1 and S1<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>3. Agonists of S1<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>1 and S1<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>3 each partially mimicked S1P\u2010induced effect in jugular C\u2010fibers, suggesting that these receptors may contribute partially to S1P\u2010induced activation effect on esophageal jugular C\u2010fiber subtype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>These data, for the first time, demonstrated a selective activation effect of S1P on vagal afferent nerve subtype in the gastrointestinal tract. This may help to better understand its role in visceral inflammatory nociception.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13359","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T18:13:54Z","timestamp":1524161634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sphingosine\u20101\u2010phosphate selectively activates vagal afferent C\u2010fiber subtype in guinea pig esophagus"],"prefix":"10.1111","volume":"30","author":[{"given":"X.","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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