naloxone and Enteritis

We evaluated and compared the effects of mu-opioid receptor agonists on mucosal fluid transport and permeability, during acute intestinal inflammation. We hypothesized that inflammation would sensitize mu-opioid receptors in the submucosal plexus and/or enterocytes enhancing the effects of mu-opioid receptor agonists. Inflammation was induced by intragastric administration of croton oil, whereas controls received saline. Fluid transport was assessed by enteropooling, and intestinal permeability by blood-to-lumen passage of [51Cr] etylenediaminetetraacetate ([51Cr] EDTA). Intestinal inflammation induced a significant increase in enteropooling (1.9 times) and permeability (2.5 times). In saline- and croton oil-treated animals, mu-opioid receptor agonists produced dose-related inhibitions of enteropooling and intestinal permeability. During inflammation, the potency of morphine increased 4.8 and 3.7 times, inhibiting enteropooling and intestinal permeability, respectively; the potencies of fentanyl and PL017 similarly increased by approximately three (enteropooling) and two times (permeability) in croton oil animals. All effects were reversed by naloxone and naloxone methiodide. The results show that inflammation increases the inhibitory potency of mu-opioid receptor agonists on secretion and permeability, suggesting a sensitization of peripheral mu-opioid receptors.

Topics: Acute Disease; Animals; Croton Oil; Dose-Response Relationship, Drug; Endorphins; Enteritis; Fentanyl; Intestinal Mucosa; Male; Mice; Morphine; Naloxone; Permeability; Receptors, Opioid, mu

The study evaluates the peripheral component of the antitransit effects of opioids during acute intestinal inflammation induced by the intragastric administration of croton oil (CO) in mice. Gastrointestinal transit was measured 3 h after CO or saline (SS) administration with a charcoal meal. In both groups, the effects of mixed (morphine, fentanyl, U-50488H) and peripherally acting (N-methylmorphine, PL017, ICI-204448) opioids and their antagonism by naloxone and naloxone methiodide were established. During inflammation, the potencies of morphine and N-methylmorphine increased 3 times, and those of fentanyl and PL017, 1.9 times. The effects were reversed by naloxone (0.1 mg/kg) and naloxone methiodide (0.3 mg/kg). No dose-response relationships could be elicited with U-50488H or ICI-204448, and their antitransit effects were analogous in SS- and CO-treated animals. These results show that during inflammation the enhanced antitransit effects of opioids are primarily mediated by interaction with opioid receptors located at peripheral sites. In addition, inflammation of the gut seems to induce a sensitization of mu-but not kappa-opioid receptors.

Topics: Animals; Croton Oil; Enteritis; Gastrointestinal Motility; Jejunum; Male; Mice; Morphine; Naloxone; Receptors, Opioid

The aim of the study was to evaluate the effects of centrally and peripherally acting opioid antagonists such as naloxone (NX), naloxone methiodide, (+)-naloxone [(+)NX], (-)-a-5,9-diethyl-2'-hydroxy-2 (3-furylmethyl)-6,7-benzomorphan and naltrindole on gastrointestinal (GI) transit in mice with diarrhea associated with intestinal inflammation. Our hypothesis was that diarrhea/inflammation could induce a release of endogenous opioid peptides that would play an inhibitory role in the physiological response to intestinal inflammation; the administration of opioid antagonists would uncover the effects of the endogenous opioid peptides on the gut. Diarrhea associated with inflammation was induced in mice by administration of croton oil (CO) although control animals received saline (SS); GI transit was evaluated with a charcoal meal. The i.p. administration of 0.1 mg/kg NX or NXME, induced a significant increase in GI transit in CO but not in SS-treated animals (P < .005). At the same dose, (+)NX had no effect either in CO or SS groups. The kappa antagonist MR-2266 (1 and 3 mg/kg) had no effect on GI transit in SS or CO animals. However, the delta antagonist naltrindole (3 mg/kg), caused a small but significant (P < .01) increase in GI transit in the CO group. These results suggest that endogenous opioid peptides are released in CO-treated animals and exert an inhibitory control of intestinal motility, which is unmasked by opioid antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Benzomorphans; Croton Oil; Diarrhea; Enteritis; Gastrointestinal Motility; Male; Mice; Naloxone; Naltrexone; Quaternary Ammonium Compounds; Receptors, Opioid, delta; Receptors, Opioid, kappa