title: Autoradiographic localisation of [3H]2-BFI imidazoline I2 binding sites in mouse brain.
abstract: Imidazoline I2 binding sites are heterogeneous in nature and have been observed in the brain of a number of species. Development of specific imidazoline I2 radioligands, such as [3H]2-BFI and [3H]BU224, that have a high affinity for the imidazoline I2 binding site, has enabled the central distribution of these sites to be mapped. Extensive studies have been conducted on the rat brain with a number of radioligands. However, to date a comprehensive analysis of imidazoline I2 ligand binding in mouse brain has not been completed. In the present work we describe levels of [3H]2-BFI specific binding found throughout the mouse brain. [3H]2-BFI (2 nM) showed discrete regional distribution which was readily displaced by saturating concentrations of the specific imidazoline I2 ligand BU224. The highest levels of [3H]2-BFI specific binding were found in the dorsal raphe, paraventricular thalamus and nucleus accumbens. Moderate levels were found throughout the lining of the aqueduct, lateral ventricle, lateral 4th ventricle, 4th ventricle, 3rd ventricle, but not the dorsal 3rd ventricle. Based on the loss of [3H]idazoxan binding in brain homogenates from monoamine oxidase-A and B (MAO-A and MAO-B) deficient mice it has been suggested that imidazoline I2 binding sites are predominantly on MAO. Consistent with this hypothesis the regional distribution of [3H]2-BFI shows some overlap with that previously reported for MAO. However, in the rat imidazoline I2 binding sites have been shown to be heterogeneous in nature and it is likely [3H]2-BFI is binding to multiple imidazoline I2 binding sites within mouse brain.
authors.affiliation: Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET, United Kingdom. nicholas.macinnes@kcl.ac.uk
authors.forename: Nicholas
authors.initials: N
authors.lastname: MacInnes
authors.forename: Sheila L
authors.initials: SL
authors.lastname: Handley
mesh_terms: D000818:Animals; D001345:Autoradiography; D001572:Benzofurans / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D019329:Idazoxan / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020644:Midline Thalamic Nuclei / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D011869:Radioligand Assay; D011903:Raphe Nuclei / Q000378:metabolism; D014316:Tritium
chemical_list: C105826:BU 224; D001572:Benzofurans; D007093:Imidazoles; D014316:Tritium; C103723:2-(2-benzofuranyl)-2-imidazoline; D019329:Idazoxan