THE INHIBITORY EFFECT OF TRIFLUOROMETHYLPHENYLPIPERAZINE ON [H-3] ACETYLCHOLINE-RELEASE IN GUINEA-PIG HIPPOCAMPAL SYNAPTOSOMES IS MEDIATED BY A 5-HYDROXYTRYPTAMINE1 RECEPTOR DISTINCT FROM 1A-SUBTYPE, 1B-SUBTYPE, AND 1C-SUBTYPE

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