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 microgram ml-1) caused a sustained increase in submaximal, electrically-evoked contractions. Higher concentrations of 5-HT (0.1-10 micrograms ml-1) initially evoked a fast, rapidly-fading contraction of the muscle. Subsequently, 5-HT 0.1-10 micrograms ml-1 caused a sustained reduction in the height of the electrically-evoked contractions. The effects of 5-HT 0.01 and 0.1 microgram ml-1 on the electrically-evoked contractions were not blocked by methysergide 0.1 microgram ml-1 or by hexamethonium 10 micrograms 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.