Distribution of [(3)H]BU224, a selective imidazoline I(2) binding site ligand, in rat brain

BU224 (2-(4,5-dihydroimidaz-2-yl)-quinoline) is a selective imidazoline I(2) binding site ligand characterised in both competition binding assays and functional studies. However, in some studies, BU224 has been reported to have a different functional effect from that seen with another selective imidazoline I(2) binding site ligand 2-BFI (2-(2-benzofuranyl)-2-imidazoline). This effect may reflect differing efficacies of the ligands or a difference in their brain distribution. The present study has investigated the distribution of the tritiated form of BU224 in rat brain and correlated this distribution with other imidazoline I(2) binding site ligands, [(3)H]idazoxan and [(3)H]2-BFI. Saturation studies revealed binding of [(3)H]BU224 was of high affinity and saturable. The central distribution of [(3)H]BU224 was similar to that previous reported for imidazoline I(2) binding site in rat brain. Autoradiography revealed that the highest levels of binding were in the arcuate nucleus, interpeduncular nucleus, area postrema, pineal gland and ependymal cell layer lining the ventricles. Correlation analysis of the binding distribution with our previous published studies revealed a highly significant correlation between [(3)H]BU224 and both [(3)H]idazoxan (r=0.94) and [(3)H]2-BFI (r=0.96). These data indicate [(3)H]BU224 labels the same population of imidazoline I(2) binding site in rat brain as seen with [(3)H]idazoxan and [(3)H]2-BFI. Therefore, the differences in functional effects observed with these compounds may reflect agonist and antagonist properties.