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

Abstract

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.

Prospective randomized double-blind trial of racecadotril compared with loperamide in elderly people with gastroenteritis living in nursing homes

“…Available drugs are represented by loperamide and racecadotril. Loperamide is an mu-opiate-receptor agonist, which prolongs orocecal and colonic transit times by disrupting the gut's electrical activity, increasing gut capacity, and delaying the passage of fluids through the small intestine [13]. Racecadotril, an enkephalinase inhibitor, is an indirect delta receptor agonist, with antisecretory activity [14,15] without activity on gut muscle [16].…”

Constipation – a difficult therapeutic problem

“…Dodatkowo zwiększa się wchłanianie wody ze światła jelita, co prowadzi do tworzenia suchych mas kało-wych. Efekt działania opioidów na różnych piętrach ukła-du pokarmowego można sprowadzić do trzech mechanizmów: spowolnienia pasażu, zwiększenia napięcia zwieraczy i odwodnienia stolca, co sumarycznie prowadzi do tworzenia się i zalegania w jelitach twardych mas kało-wych, mogących być przyczyną niedrożności przewodu pokar mowego [50][51][52][53]. Już kilkudniowe przyjmowanie opioidów może spowodować wystąpienie ZJWO.…”

The influence of opioids on gastric function: experimental and clinical studies

“…MORs are widely distributed on cell membranes in the body and are present in the central nervous system (45)(46)(47) including at the spinal level (48), on peripheral nerves (49), and in the gastrointestinal tract (41,(50)(51)(52).…”