The effects of LSD in the guinea-pig ileum. Inhibition of acetylcholine release and stimulation of smooth muscle.

The effects of lysergic acid diethylamide (LSD) on acetylcholine release and on smooth muscle tone were studied in the myenteric plexus-longitudinal muscle preparation of the guinea pig. LSD (0.01-10 microM) depressed in a concentration-dependent manner the electrically-evoked [3H]-acetylcholine outflow from strips preincubated with [3H]-choline. The maximal effect was a 45% inhibition by 1 microM LSD. The spontaneous outflow was not affected. Metitepine competitively antagonized (pA2 8.0) the LSD-induced reduction of the evoked outflow. Tolazoline and mepyramine did not affect the inhibitory action of LSD. The contractions in response to electrical stimulation were enhanced by 34% in the presence of 0.1 microM LSD. Other concentrations of LSD did not affect the twitches. LSD caused an increase in muscle tone which was antagonized non-competitively by mepyramine, metitepine and ketanserin. Ketanserin was a competitive antagonist against the histamine-induced contractions of the longitudinal muscle (pA2 8.49). The results suggest that LSD stimulates presynaptically located 5-HT receptors and thereby decreases the evoked acetylcholine release. In addition, LSD increases smooth muscle tone either directly through stimulation of H1 receptors or indirectly via histamine release.