Different sites of action for morphine, ethanol, barbital and pentobarbital within the guinea-pig ileum longitudinal muscle/myenteric plexus preparation.
Morphine, ethanol, barbital and pentobarbital reversibly inhibited in a dose-dependent manner, the electrically evoked contractions of the guinea-pig ileum longitudinal muscle/myenteric plexus (LM/MP) preparation, in vitro. The ED50s for inhibition were 0.2 microM for morphine and 120, 8 and 0.3 mM for ethanol, barbital and pentobarbital respectively. To determine whether the site of inhibition was pre- or postjunctioal we studied the effects of graded concentrations of these drugs on the contractions evoked by exogenous acetylcholine (ACh). A correlation between the inhibition of the electrically and ACh-evoked muscle contractions suggests that morphine acts primarily prejunctionally while ethanol acts both pre-and postjunctionally. The inhibition by barbital and pentobarbital, however, can be accounted completely by a postjunctional depression. These results may explain our previous observation of cross-tolerance between morphine and ethanol in this preparation, and the lack of cross-tolerance between these drugs and barbital.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001462:Barbital / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology*; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology*
D001463:Barbiturates; D000431:Ethanol; D001462:Barbital; D009020:Morphine; D010424:Pentobarbital; D000109:Acetylcholine