Characterisation and localisation of [3H]2-(2-benzofuranyl)-2-imidazoline binding in rat brain: a selective ligand for imidazoline I2 receptors.
In rat whole brain homogenates, saturation binding analysis revealed that both [3H]2-BFI (2-(2-benzofuranyl)-2-imidazoline) and [3H]idazoxan (in the presence of 5 microM rauwolscine) bound with high affinity to an apparent single population of sites. However, the Kd for [3H]2-BFI (1.74+/-0.14 nM) was significantly (P < 0.01) less than that for [3H]idazoxan (10.4+/-2.68 nM). In competition studies idazoxan, 2-BFI, BU224 (2-(4,5-dihydroimidaz-2-yl)-quinoline), amiloride and guanabenz displayed high affinity (Ki values = 7.32, 1.71, 2.08, 21.80 and 14.90 nM, respectively) for 70-80% of sites, and low microM affinity for the remaining 20-30% of sites labelled by [3H]2-BFI. In contrast, several alpha2-adrenoceptor, imidazoline I1 receptor and histamine receptor ligands exhibited only micromolar affinity for the [3H]2-BFI labelled site. Quantitative receptor autoradiography revealed high binding by [3H]2-BFI to discrete brain nuclei, notably the area postrema, interpeduncular nucleus, arcuate nucleus, mammillary peduncle, ependyma and pineal gland. These data indicate that [3H]2-BFI recognises imidazoline I2 receptors in rat brain with higher affinity and selectivity than [3H]idazoxan and thus represents a superior radioligand to [3H]idazoxan for the study of imidazoline I2 receptors.
Psychopharmacology Unit, School of Medical Sciences, University of Bristol, UK.
L A
LA
Lione
D J
DJ
Nutt
A L
AL
Hudson
D000818:Animals; D001345:Autoradiography; D001572:Benzofurans / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D019329:Idazoxan / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism*; D054755:Imidazoline Receptors; D007700:Kinetics; D008024:Ligands; D008297:Male; D008566:Membranes; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism*; D014316:Tritium
D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; D011955:Receptors, Drug; D014316:Tritium; C103723:2-(2-benzofuranyl)-2-imidazoline; D019329:Idazoxan