TY - JOUR
T1 - Active bicarbonate-dependent secretion evoked by 5-hydroxytryptamine in porcine ileal mucosa is mediated by opioid-sensitive enteric neurons
AU - Green, Benedict T.
AU - Brown, David R.
PY - 2002/9/13
Y1 - 2002/9/13
N2 - 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.
AB - 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.
KW - Bicarbonate-dependent secretion
KW - Cannabinoid
KW - Enkephalin
KW - Inflammatory mediator
KW - Prostanoid
UR - http://www.scopus.com/inward/record.url?scp=0037072574&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037072574&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(02)02249-5
DO - 10.1016/S0014-2999(02)02249-5
M3 - Article
C2 - 12231390
AN - SCOPUS:0037072574
VL - 451
SP - 185
EP - 190
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -