The topographical basis and frequency-dependence in the effect of different compounds on neurogenic contractions of the guinea-pig ileum.
The effect of tetanus on the twitch responses of the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum to electrical stimuli was investigated in the presence of naloxone and indomethacin. Naloxone was used to prevent post-tetanic twitch inhibition due to the release of endogenous opiate ligands, and indomethacin to diminish pretetanic twitch height. Twitch contractions following tetanus were potentiated in the presence of both drugs. The optimal stimulation parameters for the manifestation of post-tetanic potentiation (PTP) were determined; tetanic stimulation: 30 Hz for 25 s. supramaximal impulse intensity; twitches: 0.04 Hz, low impulse intensity. PTP was also obtained when indomethacin was replaced by noradrenaline or adenosine, i.e. by drugs whose mechanism of action also includes a presynaptic effect. Postsynaptic changes in contractility cannot fully account for the observed PTP of twitches judging from the smaller effect of tetanus on acetylcholine-evoked contractions. The hypothesis of a presynaptic origin of PTP at this muscarinic synapse was corroborated in the experiments where acetylcholine stores were labelled with [3H] choline and the release of the label was increased during PTP. Furthermore, a bioassay showed that the output of endogenous acetylcholine in the post-tetanic interval was increased in the presence of naloxone plus indomethacin but not in their absence. The fact that PTP was also observed in the absence of any drug, if the tetanic stimulation was short (10 s) and of low impulse intensity, suggested its possible physiological significance.