5-hT4 receptor agonists and δ-opioid receptor antagonists act synergistically to stimulate colonic propulsion

A. E. Foxx-Orenstein, J. G. Jin, J. R. Grider

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Opioid neurons exert a tonic restraint on inhibitory VIP/PACAP/NOS motoneurons of the enteric nervous system. A decrease in opioid peptide release during the descending phase of the peristatic reflex, which underlies propulsive activity, leads to an increase in vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and nitric oxide (NO) release and circular muscle relaxation. These effects are accentuated by opioid receptor antagonists. Endogenous opioid peptides and selective opioid δ-, κ- and μ-receptor agonists decreased the velocity of pellet propulsion in isolated segments of guinea pig colon, whereas selective antagonists increased velocity in a concentration-dependent fashion with an order of potency indicating preferential involvement of δ-receptors. 5-HT4 agonists (HTF-919 and R-093877), which also increase the velocity of propulsion, acted synergistically with the δ-receptor antagonist naltrindole; a threshold concentration of naltrindole (10 nM) shifted the concentration-response curve to HTF-919 to the left by 70-fold. A combination of 10 nM naltrindole with threshold concentrations of the 5-HT4 agonists caused significant increases in the velocity of propulsion (50 ± 7 to 77 ± 8%). We conclude that 5-HT4 agonists and opioid δ-receptor antagonists act synergistically to facilitate propulsive activity in isolated colonic segments.

Original languageEnglish (US)
Pages (from-to)G979-G983
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number5 38-5
StatePublished - 1998


  • Enteric nervous system
  • Gut motility
  • Intestinal smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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