Synergistic interaction of morphine and halothane in the guinea pig ileum: effects of pertussis toxin.

The effects of pertussis toxin on the actions of morphine and halothane in the guinea pig ileum are described. Both morphine and halothane produce a dose-related inhibition of electrically induced muscle contraction. The IC50 of morphine was unchanged by the toxin (2.1 and 2.2 X 10(-7) M in control and toxin-pretreated animals). However, the IC50 of halothane was increased from 2.1 to an extrapolated value of 9.1 vol/vol% by pertussis toxin. At high levels of inhibition the interaction between morphine and halothane was synergistic and was converted to additive in the presence of the toxin. These results demonstrate that in the myenteric longitudinal muscle preparation the effects of halothane, but not those of morphine, are mediated by the substrate for pertussis toxin, possibly a Gi membrane protein. The present study provides significant evidence that the effects of halothane on neuronal tissue are dependent upon an interaction with a specific membrane protein.