title: Characterisation of imidazoline I2 binding sites in pig brain.
abstract: The imidazoline I2 binding sites in the central nervous system have previously been described in several different species including rat, mouse, rabbit and frog. The present study has investigated the imidazoline I2 binding site, and its relationship to the monoamine oxidase isoforms, in pig whole brain and compared the results obtained with data from other species. Results from saturation binding studies revealed that the imidazoline I2-selective ligand, [3H]2BFI (2-(2-benzofuranyl)-2-imidazoline) labelled a single saturable population of sites with a KD=6.6 nM and Bmax=771.7 fmol/mg protein. The pharmacological characterisation of the sites was similar to that previously reported with a rank order of potency for the imidazoline I2 ligands of 2BFI>BU224>Idazoxan>BU226. Displacement by the imidazoline I1 ligands was low affinity and the monoamine oxidase inhibitors displaced with micromolar affinity. The majority of compounds displaced the binding in a monophasic manner, however, displacement by the putative endogenous ligand, harmane was biphasic. The relative populations of the two monoamine oxidase isoforms revealed a 10 fold greater expression of monoamine oxidase B relative to monoamine oxidase A. These data confirm the presence of imidazoline I2 binding sites in pig brain and show that their pharmacology is characteristic of that seen in other species. The proportion of monoamine oxidase A and B expressed in the pig brain is similar to that seen in the human brain therefore, given the association between imidazoline I2 binding sites and monoamine oxidase, the pig may provide a more useful model for human imidazoline I2 binding sites than other species such as the rat.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University Walk, Clifton, Bristol BS8 1TD, UK.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Anderson
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Lupo
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hudson
authors.forename: Emma S J
authors.initials: ES
authors.lastname: Robinson
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000378:metabolism / Q000494:pharmacology; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D019329:Idazoxan / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D054755:Imidazoline Receptors; D007700:Kinetics; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D010848:Picolinic Acids / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000378:metabolism*; D013552:Swine; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium
chemical_list: C105826:BU 224; D001572:Benzofurans; D002243:Carbolines; D007093:Imidazoles; D054755:Imidazoline Receptors; D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; D011955:Receptors, Drug; D013844:Thiazoles; C487767:imidazoline receptor 2; D014316:Tritium; C063456:Ro 41-1049; C059303:lazabemide; C103723:2-(2-benzofuranyl)-2-imidazoline; D003000:Clonidine; D019329:Idazoxan