Relative involvement of receptor subtypes in opioid-induced inhibition of intestinal motility in mice.
The effects of opioids on intestinal transit of a charcoal meal were assessed in mice. Morphine (s.c. or i.c.v.) produced a fulldose-response curve and DADLE (s.c. or i.c.v.) produced a dose-response curve with a reduced maximum effect. The highly selective, non-equilibrium mu antagonist, beta-funaltrexamine (beta-FNA), antagonized these effects. Nalorphine (s.c.) induced a maximal 42% inhibition of charcoal meal transit that was not antagonized by beta-FNA. Ethylketazocine (s.c.) produced a full dose-response curve, the higher doses of which were antagonized by beta-FNA. Nalorphine and ethylketazocine had no effect upon charcoal meal transit when given i.c.v.. Tolerance to morphine (s.c.) and to higher doses of ethylketazocine (s.c.) was seen in animals pretreated with a morphine pellet. These data suggest that inhibition of charcoal meal transit in mice can be mediated by a central and a peripheral mu-mediated mechanism and that a peripheral k component may also produce a limited inhibition of intestinal motility. Moreover, since a s.c. dose of beta-FNA produced a 10-and 2-fold shift in the ED50 for morphine given s.c. and i.c.v., respectively, yet an i.c.v. dose of beta-FNA produced a 6- and 200-fold shift in the ED50 for morphine given s.c. and i.c.v., respectively, the effects of a s.c. dose of morphine appear to be mediated predominantly by a peripheral, rather than a central, opioid action.
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D016314:Ethylketocyclazocine; D005769:Gastrointestinal Motility / Q000187:drug effects*; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009269:Nalorphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000032:analysis / Q000187:drug effects*
D000701:Analgesics, Opioid; D009294:Narcotics; D011957:Receptors, Opioid; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C024524:beta-funaltrexamine; D009020:Morphine; D003496:Cyclazocine; D009269:Nalorphine