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.