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 [H-3]2-BFI (2-(2-benzofuranyl)-2-imidazoline) and [H-3]idazoxan tin the presence of 5 mu M rauwolscine) bound with high affinity to an apparent single population of sites. However, the K-d for [H-3]2-BFI (1.74 +/- 0.14 nM) was significantly (P < 0.01) less than that for [H-3]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 (K-i values = 7.32, 1.71, 2.08, 21.80 and 14.90 nM, respectively) for 70-80% of sites, and low mu M affinity for the remaining 20-30% of sites labelled by [H-3]2-BFI. In contrast, several alpha(2)-adrenoceptor, imidazoline I-1 receptor and histamine receptor ligands exhibited only micromolar affinity for the [H-3]2-BFI labelled site. Quantitative receptor autoradiography revealed high binding by [H-3]2-BFI to discrete brain nuclei, notably the area postrema, interpeduncular nucleus, arcuate nucleus, mammillary peduncle, ependyma and pineal gland. These data indicate that [H-3]2-BFI recognises imidazoline I-2 receptors in rat brain with higher affinity and selectivity than [H-3]idazoxan and thus represents a superior radioligand to [H-3]idazoxan for the study of imidazoline I-2 receptors. (C) 1998 Elsevier Science B.V. All rights reserved.