Involvement of m-and k-, but not d-, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea-pig intestine 1 Opiates inhibit gastrointestinal propulsion, but it is not clear which opioid receptor types are involved in this action. For this reason, the eect of opioid receptor ± selective agonists and antagonists on intestinal peristalsis was studied. 2 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. 3 m-Opioid receptor agonists (DAMGO, morphine), k-opioid receptor agonists (ICI-204,448 and BRL-52,537) and a d-opioid receptor agonist (SNC-80) inhibited peristalsis in a concentrationrelated manner as deduced from a rise of the peristaltic pressure threshold (PPT) and a diminution of peristaltic eectiveness. 4 Experiments with the d-opioid receptor antagonists naltrindole (30 nM) and HS-378 (1 mM), the k-opioid receptor antagonist nor-binaltorphimine (30 nM) and the m-opioid receptor antagonist cyprodime (10 mM) revealed that the antiperistaltic eect of ICI-204,448 and BRL-52,537 was mediated by k-opioid receptors and that of morphine and DAMGO by m-opioid receptors. In contrast, the peristaltic motor inhibition caused by SNC-80 was unrelated to d-opioid receptor activation. 5 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. 6 The results show that the neural circuits controlling peristalsis in the guinea-pig small intestine are inhibited by endogenous and exogenous opioids acting via m-and k-, but not d-, opioid receptors.
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