title: Quantitative analysis of binding parameters of [3H]N-methylscopolamine in central nervous system of muscarinic acetylcholine receptor knockout mice.
abstract: We have studied binding parameters (Kd, Bmax) of [3H]N-methylscopolamine ([3H]NMS) in various brain regions and spinal cord of wild-type (WT) and muscarinic acetylcholine receptor (mAChR) subtype (M1-M5) knockout (KO) mice. In the M1-M4 KO mice, the number of [3H]NMS binding sites (Bmax) was decreased throughout the central nervous system (CNS) with significant regional differences. Our results collectively suggest that M1 receptor was present in a relatively high density in the cerebral cortex and hippocampus, and the densities of M1 and M4 subtypes were highest in the corpus striatum. M2 receptor appeared to be the major subtype in the thalamus, hypothalamus, midbrain, pons-medulla, cerebellum and spinal cord. These findings may contribute significantly not only to the further understanding of the physiological roles of mAChR subtypes in the central cholinergic functions, but also to the development of selective therapeutic agents targeting specific subtype.
authors.affiliation: Department of Biopharmaceutical Sciences and COE Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Oki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takagi
authors.forename: Sayuri
authors.initials: S
authors.lastname: Inagaki
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Toshiya
authors.initials: T
authors.lastname: Manabe
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsui
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D018345:Mice, Knockout / Q000378:metabolism; D019832:N-Methylscopolamine / Q000493:pharmacokinetics*; D010276:Parasympatholytics / Q000493:pharmacokinetics; D011485:Protein Binding; D011869:Radioligand Assay / Q000379:methods; D011976:Receptors, Muscarinic / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D014316:Tritium; D019832:N-Methylscopolamine