title: Remarkable selectivity of the in vivo binding of [3H]Ro15-4513 to α5 subtype of benzodiazepine receptor in the living mouse brain.
abstract: To evaluate the binding characteristics of [(3)H]Ro15-4513 with the central benzodiazepine (BZ) receptor, inhibition experiments of [(3)H]Ro15-1788 and [(3)H]Ro15-4513 were performed both in vitro and in vivo, using two BZ ligands, flunitrazepam (FNP), and ethyl-β-carboline-3-carboxylate (β-CCE). FNP inhibited the binding of [(3)H]Ro15-1788 and [(3)H]Ro15-4513 in a dose-dependent manner in the mouse cerebral cortex, hippocampus, and cerebellum, both in vitro and in vivo. β-CCE also inhibited the binding of [(3)H]Ro15-1788 and [(3)H]Ro15-4513 in all the aforementioned brain regions in vitro. However, in vivo, β-CCE inhibited the binding of [(3)H]Ro15-4513 in the cerebral cortex and cerebellum, but not in the hippocampus, even at an injected dose of up to 1mg/kg. In contrast, more than 50% of the in vivo binding of [(3)H]Ro15-1788 was inhibited by 1 mg/kg of β-CCE in all regions. The time-activity curve of [(3)H]Ro15-4513 in the hippocampus also showed no alteration of the peak uptake between the control group and 0.3 mg/kg of β-CCE coinjected group. These results indicated that the binding characteristics of [(3)H]Ro15-4513 with the BZ receptor differed markedly between the in vitro and in vivo condition, and the selectivity of [(3)H]Ro15-4513 binding to α5 subtype of BZ receptor in the mouse brain seemed to be remarkable under the in vivo condition.
authors.affiliation: Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. momosaki@sahs.med.osaka-u.ac.jp
authors.forename: Sotaro
authors.initials: S
authors.lastname: Momosaki
authors.forename: Rie
authors.initials: R
authors.lastname: Hosoi
authors.forename: Kohji
authors.initials: K
authors.lastname: Abe
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue
mesh_terms: D000345:Affinity Labels / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000378:metabolism* / Q000494:pharmacology*; D001569:Benzodiazepines / Q000378:metabolism* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000378:metabolism / Q000494:pharmacology; D005445:Flunitrazepam / Q000494:pharmacology; D008297:Male; D051379:Mice; D021122:Protein Subunits / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D001386:Azides; D002243:Carbolines; D021122:Protein Subunits; D011963:Receptors, GABA-A; D014316:Tritium; D001569:Benzodiazepines; D005442:Flumazenil; D005445:Flunitrazepam; C024915:beta-carboline-3-carboxylic acid ethyl ester; C042957:Ro 15-4513