Abstract
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-Pen2,5]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-Pen2,5]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.
Original language | English (US) |
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Pages (from-to) | 185-190 |
Number of pages | 6 |
Journal | European Journal of Pharmacology |
Volume | 451 |
Issue number | 2 |
DOIs | |
State | Published - Sep 13 2002 |
Bibliographical note
Funding Information:The authors thank Dr. Scott M. O'Grady (Department of Animal Science-Physiology, University of Minnesota) for expert technical advice during the execution of this project. This study was funded in part by NIH/NIDA grant R01 DA-10200. B.T.G. was a predoctoral trainee supported by ADAMHA/NIDA Psychoneuroimmunology and Substance Abuse training grant T32 DA07239.
Keywords
- Bicarbonate-dependent secretion
- Cannabinoid
- Enkephalin
- Inflammatory mediator
- Prostanoid