Modulatory action on the twitch responses of the guinea-pig ileum of endogenous substances released by high frequency electrical stimulation.

Inhibition of twitch responses of the guinea-pig isolated ileum to low frequency electrical stimulation (0.2 Hz) followed the interpolation of a 30 sec period of high frequency electrical stimulation (HFS; 7.5 and 10 Hz). Indomethacin (1-2.5 microM) potentiated this inhibition of twitch following HFS at 10 Hz but not 7.5 Hz. The addition of naloxone (1 microM) markedly antagonised the post-HFS inhibition caused by both frequencies of stimulation. Metoclopramide (10 microM), which was shown to have selective antagonist properties on prejunctional ACh receptors (pA2 = 5.1), reduced the post-HFS inhibition of twitch when added with the other antagonists and shortened the time course of recovery. The inhibition of twitch responses following the interpolation of ACh (680 nM) for 30 sec was unaffected by indomethacin and naloxone but was markedly antagonised by metoclopramide. Thus, HFS release in addition to ACh, prostaglandins which potentiate the twitch response and an opiate receptor ligand which inhibits transmitter release. The use of guanethidine (10 microM) in the present experiments precluded the involvement of noradrenaline.