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.

Abstract

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.