Sphingosine-1-phosphate selectively activates vagal afferent C-fiber subtype in guinea pig esophagus

BACKGROUND: Activation and sensitization of visceral afferent nerves by inflammatory mediators play important roles in visceral nociception. Sphingosine-1-phosphate (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. METHODS: Extracellular single-unit recordings were performed in ex vivo guinea pig esophageal-vagal preparations. The action potentials (APs) 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 (S1PR1-3) in esophageal-labeled vagal nodose and jugular neurons was studied by single-cell RT-PCR. KEY RESULTS: Sphingosine-1-phosphate evoked AP discharges in almost all esophageal jugular but not nodose C-fibers without changing their responses to esophageal distension. Esophageal-labeled vagal nodose and jugular neurons highly expressed transcripts of S1PR1 and S1PR3. Agonists of S1PR1 and S1PR3 each partially mimicked S1P-induced effect in jugular C-fibers, suggesting that these receptors may contribute partially to S1P-induced activation effect on esophageal jugular C-fiber subtype. CONCLUSIONS & INFERENCES: 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.