title: Binding of selective antagonists to four muscarinic receptors (M1 to M4) in rat forebrain.
abstract: To compare the proportions of four muscarinic receptors in different rat brain regions, we used competition curves with four selective antagonists, at 1-[N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) binding equilibrium and after allowing [3H]NMS dissociation for 35 min. Himbacine and methoctramine were shown to discriminate two muscarinic receptor subtypes having a high affinity for 4-diphenylacetoxy-N-methylpiperidine methiodide and hexahydrosiladifenidol, intermediate affinity for pirenzepine, and low affinity for AF-DX 116. One M4 subtype had a high affinity for himbacine and methoctramine; it was found predominantly in homogenates from rat striatum (46% of total [3H]NMS receptors) and in lower proportion in cortex (33% of [3H]NMS receptors) and hippocampus (16% of [3H]NMS receptors). Its binding properties were identical to those of muscarinic receptors in the neuroblastoma x glioma NG 108-15 hybrid, suggesting that it was encoded by m4 mRNA. The M3 subtype (typically found in rat pancreas, a tissue expressing the m3 mRNA) had a low affinity for himbacine and methoctramine and represented about 10% of all [3H]NMS receptors in rat brain cortex, hippocampus, striatum, and cerebellum. M1 and M2 receptors were identified in rat brain by their high affinity for pirenzepine and AF-DX 116, respectively.
authors.affiliation: Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Waelbroeck
authors.forename: M
authors.initials: M
authors.lastname: Tastenoy
authors.forename: J
authors.initials: J
authors.lastname: Camus
authors.forename: J
authors.initials: J
authors.lastname: Christophe
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003959:Diamines / Q000494:pharmacology*; D005663:Furans; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects; D019832:N-Methylscopolamine; D009281:Naphthalenes; D010276:Parasympatholytics / Q000494:pharmacology*; D010880:Piperidines; D051381:Rats; D011976:Receptors, Muscarinic / Q000145:classification / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000470:Alkaloids; D003959:Diamines; D005663:Furans; D009281:Naphthalenes; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; C048172:himbacine; C054938:methoctramine; D019832:N-Methylscopolamine