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Three different ways in which 5‐hydroxytryptamine can affect cholinergic activity in guinea‐pig isolated ileum

The effects of 5‐hydroxytryptamine (5‐HT) have been studied on electrically‐evoked contractions mediated by cholinergic nerves in guinea‐pig isolated ileum. Low concentrations of 5‐HT (0.0001‐0.01 μg ml−1) caused a sustained increase in submaximal, electrically‐evoked contractions. Higher concentrations of 5‐HT (0.1–10 μg ml−1) initially evoked a fast, rapidly‐fading contraction of the muscle. Subsequently, 5‐HT 0.1–10 μg ml−1 caused a sustained reduction in the height of the electrically‐evoked contractions. The effects of 5‐HT 0.01 and 0.1 μg ml−1 on the electrically‐evoked contractions were not blocked by methysergide 0.1 μg ml−1 or by hexamethonium 10 μg ml−1, and may be due to changes in neuronal acetylcholine (ACh) release, since contractions evoked by exogenous ACh were unaffected by 5‐HT. The results therefore imply that 5‐HT can affect gut cholinergic activity in at least three different ways, two of which may modulate evoked ACh release by mechanisms which may be insensitive to tachyphylaxis.