LSL-60101, A SELECTIVE LIGAND FOR IMIDAZOLINE I-2 RECEPTORS, ON GLIAL FIBRILLARY ACIDIC PROTEIN-CONCENTRATION

The concentration of the astrocytic marker, glial fibrillary acidic protein (GFAP) was quantitated by immunoblotting (Western blotting) in the rat brain after treatment with the novel ligand for imidazoline I-2 receptors LSL 60101 [2-(2-benzofuranyl)imidazole] and its 6-methoxy derivative LSL 60125. Chronic (7-21 days), but not acute (1 day) or short-term (3 days), treatment with LSL 60101 (10 mg/kg i.p.) markedly increased (44-49%) GFAP immunoreactivity in the rat cerebral cortex. In contrast, chronic (7 days) treatment with LSL 60125 (10 mg/kg i.p.) did not significantly modify GFAP concentrations. In vitro, both drugs displayed moderate high affinity and high selectivity for imidazoline I-2 receptors versus alpha(2)-adrenoceptors; however, only chronic treatment with LSL 60101 (10 mg/kg i.p.) but not with LSL 60125 (10 mg/kg i.p.) was associated with an up-regulation of imidazoline I-2 receptors. These data indicate that glial imidazoline I-2 receptors may have a direct physiological function related to GFAP expression and that LSL 60101 could be a good tool for the study of the implication of these receptors on astrocyte activation and neuronal regeneration.