title: High affinity binding of [3H]6-nitroquipazine to cortical membranes in the rat: inhibition by 5-hydroxytryptamine and 5-hydroxytryptamine uptake inhibitors.
abstract: [3H]6-Nitroquipazine is a new, suitable radioligand for studying the uptake system for 5-hydroxytryptamine (5-HT; serotonin). In the present study, inhibition by drugs of the binding of [3H]6-nitroquipazine to uptake sites for 5-HT in the cerebral cortex of the rat was investigated. The inhibition of 5-HT and several inhibitors of the uptake of 5-HT (paroxetine, clomipramine, citalopram, Z-norzimelidine, fluoxetine, imipramine, desipramine and 5-methoxytryptoline) against the binding of [3H]6-nitroquipazine to membranes from the cortex of the rat were the same and competition curves indicated a single population of binding sites. The addition of 5-HT and the tricyclic inhibitors of the uptake of 5-HT, imipramine, clomipramine and desipramine, all produced changes in the apparent dissociation constant (Kd), without changes in the number of binding sites (Bmax). Also, the non-tricyclic inhibitors of the uptake of 5-HT, paroxetine, citalopram, fluoxetine and Z-norzimelidine, and 5-methoxytryptoline, all produced changes in Kd values without changes in the Bmax. These results suggest that all the drugs used in this experiment exhibited competitive interactions with the binding of [3H]6-nitroquipazine to uptake sites for 5-HT in the brain of the rat. These drugs may bind to common binding sites, which are likely to represent the substrate recognition sites for the uptake of 5-HT.
authors.affiliation: Department of Radiopharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Fukuyama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Goromaru
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011814:Quipazine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D012702:Serotonin Antagonists; D012701:Serotonin; D011814:Quipazine; C031227:6-nitroquipazine