5‐Hydroxytryptamine3 Receptors Sited on Cholinergic Axon Terminals of Human Cerebral Cortex Mediate Inhibition of Acetylcholine Release

Abstract

Synaptosomes prepared from freshly obtained human cerebral cortex and labeled with [³H]choline have been used to investigate the modulation of [3H]acetylcholine ([³H]ACh) release by 5-hydroxytryptamine (5-HT). The Ca²⁺-dependent release of [³H]-ACh occurring when synaptosomes were exposed in supervision to 15 mM KCl was inhibited by 5-HT (0.01-1 μM) in a concentration-dependent manner. The effect of 5-HT was mimicked by 1-phenylbiguanide, a 5-HT₃ receptor agonist, but not by 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT_1A receptor agonist. The 5-HT₃ receptor antagonists tropisetron and ondansetron blocked the effect of 5-HT, whereas spiperone and ketanserin were ineffective. It is suggested that cholinergic axon terminals in the human cerebral cortex possess 5-HT receptors that mediate inhibition of ACh release and appear to belong to the 5-HT₃ type.