The effect of indomethacin on the release of prostaglandin E2 and acetylcholine from guinea-pig isolated ileum at rest and during field stimulation.

1 Guinea-pig ileum suspended in Krebs solution showed a continuous increase of tone which was lost by changing the bath fluid. Prostaglandin E(2) was released from the ileum during incubation, and its concentration in the bath fluid appeared to correlate with the increase in tone.2 Supramaximal field stimulation (10 Hz) resulted in increased release of prostaglandin E(2) from the ileum. At lower rates of stimulation, the increase in the release of E(2) compared with the resting output was not significant.3 Indomethacin (1 and 10 mug/ml) produced a significant, dose-related reduction of the amount of prostaglandin E(2) measured in the bath fluid at rest and with field stimulation. Indomethacin inhibited the contraction of the ileum during incubation in Krebs solution.4 Indomethacin (10 and 20 mug/ml) had no significant effect on the release of acetylcholine during field stimulation, but reduced the resting output of acetylcholine from guinea-pig ileum in some experiments.5 The results are discussed in the context of the role ascribed to prostaglandins as physiological modulators in transmitter release. No evidence for a prostaglandin-mediated negative feedback mechanism on acetylcholine release was obtained.