TY - JOUR
T1 - 5-hT4 receptor agonists and δ-opioid receptor antagonists act synergistically to stimulate colonic propulsion
AU - Foxx-Orenstein, A. E.
AU - Jin, J. G.
AU - Grider, J. R.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
KW - Enteric nervous system
KW - Gut motility
KW - Intestinal smooth muscle
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U2 - 10.1152/ajpgi.1998.275.5.g979
DO - 10.1152/ajpgi.1998.275.5.g979
M3 - Article
C2 - 9815027
AN - SCOPUS:0032209507
SN - 0193-1857
VL - 275
SP - G979-G983
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 5 38-5
ER -