The role of supersensitivity to acetyl- choline in the production of tolerance to morphine in stimulated guinea-pig ileum.

1 Morphine caused a dose-dependent reduction in both the height of contraction and acetylcholine release from coaxially stimulated strips of guinea-pig ileum.2 Exposure of the tissue to morphine for 90 min produced acute tolerance to the effect of subsequent doses of morphine on contraction height.3 There was no change in the ability of morphine to suppress acetylcholine release.4 The responses of morphine-tolerant ileum to exogenous acetylcholine were enhanced 3 to 10-fold.5 If the ileum did not show tolerance to morphine it did not become more sensitive to acetylcholine.6 The results presented suggest that tolerance to morphine could result from a form of disuse supersensitivity.