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 microM, increased short-circuit current by 58 +/- 7 microA/cm(2) 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 HCO(3)(-)-deficient media. 5-HT action was attenuated by saxitoxin in tissues bathed in Cl(-)-free media, but not HCO(3)-free media. The delta-opioid receptor agonist [D-Pen(2,5)]enkephalin (0.1 microM) blunted the 5-HT change in short-circuit current by a mechanism sensitive to the delta-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 HCO(3)(-)-dependent ion transport through a mechanism involving prostanoids and an enteric neural pathway modulated by opioids.
Green
Benedict T
BT
Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, 1988 Fitch Avenue, St. Paul, MN 55108-6010, USA.
Brown
David R
DR
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology; D017615:Enteric Nervous System / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine
D000701:Analgesics, Opioid; D001639:Bicarbonates; D002186:Cannabinoids; D017465:Receptors, Opioid, delta; D012701:Serotonin