The Inhibitory Effect of Trifluoromethylphenylpiperazine on [3H]Acetylcholine Release in Guinea Pig Hippocampal Synaptosomes Is Mediated by a 5‐Hydroxytryptamine1 Receptor Distinct from 1A, 1B, and 1C Subtypes

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Abstract
The effect of the serotonergic receptor agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP) was studied on the K+-evoked [3H]acetylcholine ([3H]ACh) release from guinea pig hippocampal synaptosomes loaded with [3H]choline. TFMPP (5–1,000 μM) inhibited the evoked ACh release in a dose-dependent manner (IC50= 81.8 μM). The inhibitory effect of TFMPP was mimicked by CGS-12066B (10, 30, and 100 μM), a 5-hydroxytryptamine1B (5-HT1B)/5-HT1D receptor agonist; 1-(m-chlorophenyl)piperazine (100 μM), a 5-HT1C/5-HT1B receptor agonist; and 5-carboxamidotryptamine (10 μM), a nonselective 5-HT1 receptor agonist. 8-Hydroxy-2-(di-n-propylamino)tetralin (10 and 100 μM), a 5-HT1A receptor agonist, and quipazine (10 and 100 μM), a 5-HT2 receptor agonist, did not have any significant effect. Serotonergic antagonists, such as dihydroergotamine (0.1 and 1 μM), metergoline (0.1 μM), methysergide (0.5 and 1 μM), or yohimbine (1 and 10 μM), blocked the TFMPP effect dose-dependently. In contrast, methiotepine (0.3 and 1 μM), propranolol (1 μM), ketanserin (0.1 μM), mesulergine (0.1 μM), ICS 205930 (0.1 and 1 μM), and spiroperidol (1 and 7 μM) did not affect the TFMPP-induced inhibition of the evoked ACh release. These data suggest that, in guinea pig hippocampus, the K+-evoked ACh release is modulated by a 5-HT1 receptor distinct from the 5-HT1A, 5-HT1B, and 5-HT1C subtypes.