CHARACTERIZATION AND LOCALIZATION OF [H-3]2-(2-BENZOFURANYL)-2-IMIDAZOLINE BINDING IN RAT-BRAIN - A SELECTIVE LIGAND FOR IMIDAZOLINE I-2 RECEPTORS

In rat whole brain homogenates, saturation binding analysis revealed t hat both [H-3]2-BFI (2-(2-benzofuranyl)-2-imidazoline) and [H-3]idazox an 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-B FI (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-B FI, BU224 (2-(4,5-dihydroimidaz-2-yl)-quinoline), amiloride and guanab enz 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, se veral alpha(2)-adrenoceptor, imidazoline I-1 receptor and histamine re ceptor ligands exhibited only micromolar affinity for the [H-3]2-BFI l abelled site. Quantitative receptor autoradiography revealed high bind ing by [H-3]2-BFI to discrete brain nuclei, notably the area postrema, interpeduncular nucleus, arcuate nucleus, mammillary peduncle, ependy ma and pineal gland. These data indicate that [H-3]2-BFI recognises im idazoline I-2 receptors in rat brain with higher affinity and selectiv ity than [H-3]idazoxan and thus represents a superior radioligand to [ H-3]idazoxan for the study of imidazoline I-2 receptors. (C) 1998 Else vier Science B.V. All rights reserved.