Effects of some cholinergic drugs on the actions of morphine on the ileum of the guinea-pig in vitro.

The sensitivity of the isolated, electrically stimulated guinea-pig ileum to acetylcholine aan physostigmein was found not to be reduced during 'dependence' or 'withdrawal' responses to morphine. There was no evidence that exaggerated release of acetylcholine occurred following withdrawal of high concentrations of morphine from 'dependent' longitudinal muscle strips incubated with 14C-choline. These data cast doubt on the hypothesis put forward by Paton in 1963to explain the development of 'tolerance' and 'dependence' to morphine in the ileum. The potency of morphine in producing responses of the ileum was reduced in the presence of raised concentrations of calcium, indicating that the effect of morphine may be mediated via a calcium-sensitive step.