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Release of endogenous 5‐hydroxytryptamine from the myenteric plexus of the guinea‐pig isolated small intestine

1 The presence of 5‐hydroxytryptamine (5‐HT) and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) in, and the release of these substances from, the myenteric plexus‐longitudinal muscle (MPLM) layer of the guinea‐pig isolated small intestine were investigated. 5‐HT and 5‐HIAA were measured by high performance liquid chromatography and electrochemical detection. 2 Freshly prepared MPLM contained measurable amounts of 5‐HT and 5‐HIAA. For the release experiments, the MPLM was incubated in a medium containing the 5‐HT uptake inhibitor fluoxetine and the monoamine oxidase inhibitor nialamide; this led to a decrease in the 5‐HIAA content of the MPLM whereas the 5‐HT content remained unchanged. 3 There was a spontaneous release of 5‐HT and 5‐HIAA from the MPLM. The release of 5‐HT was so small that it was just detectable; it seemed equivalent to about 0.8% of the tissue stores released per min. 4 Depolarization of the tissue by increasing the [K+] or by exposing it to veratridine enhanced the release of 5‐HT in a Ca2+‐dependent manner whereas the release of 5‐HIAA was not increased. Tetrodotoxin inhibited the veratridine‐evoked release of 5‐HT but did not affect the K+‐evoked release of 5‐HT. 5 The presence of 5‐HT in myenteric neurones and the characteristics of the release of 5‐HT from these neurones strongly support the hypothesis that 5‐HT is an enteric neurotransmitter.