Involvement of mu- and kappa-, but not delta-, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea-pig intestine.
Opiates inhibit gastrointestinal propulsion, but it is not clear which opioid receptor types are involved in this action. For this reason, the effect of opioid receptor - selective agonists and antagonists on intestinal peristalsis was studied. Peristalsis in isolated segments of the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the intraluminal pressure changes associated with the peristaltic waves. Mu-opioid receptor agonists (DAMGO, morphine), kappa-opioid receptor agonists (ICI-204,448 and BRL-52,537) and a delta-opioid receptor agonist (SNC-80) inhibited peristalsis in a concentration-related manner as deduced from a rise of the peristaltic pressure threshold (PPT) and a diminution of peristaltic effectiveness. Experiments with the delta-opioid receptor antagonists naltrindole (30 nM) and HS-378 (1 microM), the kappa-opioid receptor antagonist nor-binaltorphimine (30 nM) and the mu-opioid receptor antagonist cyprodime (10 microM) revealed that the antiperistaltic effect of ICI-204,448 and BRL-52,537 was mediated by kappa-opioid receptors and that of morphine and DAMGO by mu-opioid receptors. In contrast, the peristaltic motor inhibition caused by SNC-80 was unrelated to delta-opioid receptor activation. Cyprodime and nor-binaltorphimine, but not naltrindole and HS-378, were per se able to stimulate intestinal peristalsis as deduced from a decrease in PPT. The results show that the neural circuits controlling peristalsis in the guinea-pig small intestine are inhibited by endogenous and exogenous opioids acting via mu- and kappa-, but not delta-, opioid receptors.
Shahbazian
Anaid
A
Department of Experimental and Clinical Pharmacology, University of Graz, A-8010 Graz, Austria. peter.holzer@uni-graz.at
Heinemann
Akos
A
Schmidhammer
Helmut
H
Beubler
Eckhard
E
Holzer-Petsche
Ulrike
U
Holzer
Peter
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D007583:Jejunum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology / Q000502:physiology*; D010528:Peristalsis / Q000187:drug effects* / Q000502:physiology; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology
D009292:Narcotic Antagonists; D009294:Narcotics; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu