Involvement of μ ‐ and κ ‐, but not δ ‐, 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. μ‐Opioid receptor agonists (DAMGO, morphine), κ‐opioid receptor agonists (ICI‐204,448 and BRL‐52,537) and a δ‐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 δ‐opioid receptor antagonists naltrindole (30 n M ) and HS‐378 (1 μ M ), the κ‐opioid receptor antagonist nor‐binaltorphimine (30 n M ) and the μ‐opioid receptor antagonist cyprodime (10 μ M ) revealed that the antiperistaltic effect of ICI‐204,448 and BRL‐52,537 was mediated by κ‐opioid receptors and that of morphine and DAMGO by μ‐opioid receptors. In contrast, the peristaltic motor inhibition caused by SNC‐80 was unrelated to δ‐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 μ‐ and κ‐, but not δ‐, opioid receptors.British Journal of Pharmacology (2002) 135 , 741–750; doi: 10.1038/sj.bjp.0704527