Picric acid functions as a releaser of [14C]acetylcholine in isolated ileal synaptosomal preparations of guinea-pig.

Abstract

The effect of picric acid on the release of [14C]acetylcholine has been investigated in isolated ileal synaptosomes of guinea-pig. Nicotine, high K-depolarization (50 mM KCl) and electrical field stimulation were employed to characterize the specificity of picric acid. Picric acid induced the release of labelled acetylcholine in a dose-dependent manner and this action was negated by the removal of calcium ions from the bathing medium. Tetrodotoxin (0.1 microM) abolished the actions of picric acid, nicotine or electrical field stimulation (0.1 Hz). It reduced but did not totally suppress the effect of high K-depolarization. Agents capable of affecting the content of cyclic AMP, such as forskolin and alloxan, modified the effects of picric acid or nicotine but did not influence the effects of high K-depolarization or electrical field stimulation. Indomethacin, at a concentration (1 microM) effective in inhibiting the synthesis of prostaglandins, reduced the release of acetylcholine evoked by picric acid or nicotine, but did not affect the responses to high K-depolarization or electrical field stimulation. [3H]5-hydroxytryptamine was also released by high K-depolarization at a concentration sufficient to induce the release of acetylcholine. Similar results were obtained when the frequency of electrical field stimulation was raised to 10 Hz. However, picric acid did not initiate the release of 5-hydroxytryptamine. These results suggest that picric acid functions as a releaser of acetylcholine through a mechanism different from that of other stimulants.