Active bicarbonate-dependent secretion evoked by 5-hydroxytryptamine in porcine ileal mucosa is mediated by opioid-sensitive enteric neurons

5-Hydroxytryptamine (5-HT) mediates intestinal hypersecretion associated with infection and inflammation. We tested the hypothesis that 5-HT-induced anion secretion is mediated by an opioid-sensitive enteric neural circuit. 5-HT, at a contraluminal concentration of 10 μM, increased short-circuit current by 58±7 μA/cm² in sheets of porcine ileal mucosa with attached inner submucosal plexus. Responses to 5-HT were inhibited by saxitoxin or indomethacin, and reduced in tissues bathed in Cl^-- or HCO₃^--deficient media. 5-HT action was attenuated by saxitoxin in tissues bathed in Cl^--free media, but not HCO₃-free media. The δ-opioid receptor agonist [D-Pen^2,5]enkephalin (0.1 μM) blunted the 5-HT change in short-circuit current by a mechanism sensitive to the δ-opioid receptor antagonist naltrindole. The inhibitory actions of [D-Pen^2,5]enkephalin and saxitoxin were not additive. These results suggest that 5-HT stimulates HCO₃^--dependent ion transport through a mechanism involving prostanoids and an enteric neural pathway modulated by opioids.