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.
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 microM) inhibited the evoked ACh release in a dose-dependent manner (IC50 = 81.8 microM). The inhibitory effect of TFMPP was mimicked by CGS-12066B (10, 30, and 100 microM), a 5-hydroxytryptamine1B (5-HT1B)/5-HT1D receptor agonist; 1-(m-chlorophenyl)piperazine (100 microM), a 5-HT1C/5-HT1B receptor agonist; and 5-carboxamidotryptamine (10 microM), a nonselective 5-HT1 receptor agonist. 8-Hydroxy-2-(di-n-propylamino)tetralin (10 and 100 microM), a 5-HT1A receptor agonist, and quipazine (10 and 100 microM), a 5-HT2 receptor agonist, did not have any significant effect. Serotonergic antagonists, such as dihydroergotamine (0.1 and 1 microM), metergoline (0.1 microM), methysergide (0.5 and 1 microM), or yohimbine (1 and 10 microM), blocked the TFMPP effect dose-dependently. In contrast, methiotepine (0.3 and 1 microM), propranolol (1 microM), ketanserin (0.1 microM), mesulergine (0.1 microM), ICS 205930 (0.1 and 1 microM), and spiroperidol (1 and 7 microM) 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.
Harel-Dupas
C
C
Unité de Pharmacologie Neuro-Immuno-Endocrinienne de l'Institut Pasteur, Paris, France.
Cloëz
I
I
Fillion
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D010879:Piperazines; D011810:Quinoxalines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C052561:CGS 12066B; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D011814:Quipazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; D000109:Acetylcholine; C015068:1-(3-chlorophenyl)piperazine; D011188:Potassium