Peripheral effects of naloxone in mice with acute diarrhea associated with intestinal inflammation.
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)
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Department of Anaesthesiology, Hospital Universitario del Mar, Barcelona, Spain.
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Puig
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D000208:Acute Disease; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D003436:Croton Oil; D003967:Diarrhea / Q000188:drug therapy*; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D051379:Mice; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors
D001575:Benzomorphans; D000644:Quaternary Ammonium Compounds; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C027247:MR 2266; D009271:Naltrexone; C041269:N-methylnaloxone; D003436:Croton Oil; C055382:naltrindole