title: Differential [(3)H]idazoxan and [(3)H]2-(2-benzofuranyl)-2-imidazoline (2-BFI) binding to imidazoline I(2) receptors in human postmortem frontal cortex.
abstract: [(3)H]2-(2-benzofuranyl)-2-imidazoline (2-BFI) and [(3)H]idazoxan are the most used tools to characterise imidazoline I(2) receptors. We evaluated the binding of both radioligands to human postmortem frontal cortex membranes. Saturation binding analyses revealed that [(3)H]idazoxan (in the presence of 2 microM efaroxan to avoid radioligand binding to alpha(2)-adrenoceptors and imidazoline I(1) receptors) and [(3)H]2-BFI bound with high affinity to an apparent single population of sites. However, in competition studies whereas [(3)H]idazoxan (10 nM) binding was displaced monophasically by idazoxan and 2-BFI, both drugs displayed biphasic curves for [(3)H]2-BFI (1 nM). The proportion of the low-affinity binding site increased from 17% to 25% when 10 nM [(3)H]2-BFI was displaced by idazoxan. Amiloride inhibited [(3)H]2-BFI (10 nM) binding with low affinity and in a monophasic way. These data indicate that [(3)H]2-BFI recognises in human postmortem brain membranes a second binding site different from the imidazoline I(2) receptors labelled by [(3)H]idazoxan.
authors.affiliation: Department of Pharmacology, University of the Basque Country, E-48940 Leioa, Bizkaia, Spain. kfbcahel@lg.ehu.es
authors.forename: L F
authors.initials: LF
authors.lastname: Callado
authors.forename: A I
authors.initials: AI
authors.lastname: Maeztu
authors.forename: J
authors.initials: J
authors.lastname: Ballesteros
authors.forename: M
authors.initials: M
authors.lastname: Gutiérrez
authors.forename: J J
authors.initials: JJ
authors.lastname: Meana
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology; D001344:Autopsy; D001572:Benzofurans / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019329:Idazoxan / Q000378:metabolism* / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism* / Q000494:pharmacology; D054755:Imidazoline Receptors; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000378:metabolism*; D014316:Tritium
chemical_list: D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D014316:Tritium; C103723:2-(2-benzofuranyl)-2-imidazoline; D019329:Idazoxan