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.