Relative involvement of receptor subtypes in opioid-induced inhibition of gastrointestinal transit in mice
Ward, S.J.; Takemori, A.E.
Journal of Pharmacology and Experimental Therapeutics 224(2): 359-363
1983
ISSN/ISBN: 0022-3565 PMID: 6296358 Document Number: 202014
The effects of a .mu.-agonist morphine .kappa.-agonists ethylketazocine and nalorphine and a .delta.-agonist D-Ala2-D-Leu5-enkephalin on gastrointestinal transit of a charcoal meal were assessed in mice. When given either i.c.v. or s.c., morphine produced a full dose-response curve and D-Ala-D-Leu5-enkephalin produced a dose-response curve with a reduced maximum effect. These effects were antagonized by the highly selective, nonequilibrium .mu.-antagonist .beta.-funaltrexamine (.beta.-FNA). Nalorphine (s.c.) induced a maximal 40% inhibition of charcoal meal transit that was not antagonized by .beta.-FNA. Nalorphine had no effect upon transit when given i.c.v. Ethylketazocine produced a full dose-response curve when given s.c., the higher doses being antagonized by .beta.-FNA. A high dose of ethylketazocine i.c.v. produced a small inhibition of charcoal meal transit that was reduced in .beta.-FNA-pretreated animals. In animals pretreated with a morphine pellet, tolerance to morphine (s.c.) and to higher doses of ethylketazocine (s.c.) was seen. A central and a peripheral .mu.-mediated component in the inhibition of charcoal meal transit in mice apparently exists and a peripheral .kappa. component may produce a limited inhibition of gastrointestinal transit. Inasmuch as a s.c. dose of .beta.-FNA produced a 10-fold and no significant shift in the ED50 for morphine given s.c. and i.c.v., respectively, 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.