The effects of chronic imidazoline drug treatment on glial fibrillary acidic protein concentrations in rat brain

1 The concentration of the astrocytic marker, glial fibrillary acidic protein (GFAP) was quantitated by immunoblotting (western blotting) in the rat brain after treatment with various imidazoline drugs and other agents. 2 Chronic (7 days) but not acute (1 day) treatment with the imidazoline drugs, cirazoline (1 mg kg−1, i.p.) and idazoxan (10 mg kg−1, i.p.), but not with the structurally related α2‐adrenoceptor antagonists, RX821002 (2‐methoxy idazoxan) (10 mg kg−1, i.p.) and efaroxan (10 mg kg−1, i.p.), markedly increased (45%) GFAP immunoreactivity in the rat cerebral cortex. Chronic treatment (7 days) with yohimbine (10 mg kg−1, i.p.), a non‐imidazoline α2‐adrenoceptor antagonist, did not significantly modify GFAP immunoreactivity in the cerebral cortex. 3 Chronic treatment (7 days) with cirazoline and idazoxan did not alter the density of brain monoamine oxidase (MAO)‐B sites labelled by [3H]‐Ro 19–6327 (lazabemide), another relevant astroglial marker. Moreover, these imidazoline drug treatments did not modify the levels of α‐tubulin in the cerebral cortex. These negative results reinforced the specificity of the effects of imidazoline drugs on GFAP. 4 Irreversible inactivation of brain α2‐adrenoceptors (and other neurotransmitters receptors) after treatment with an optimal dose of the peptide‐coupling agent EEDQ (1.6 mg kg−1, i.p., for 6–24 h) did not alter GFAP immunoreactivity in the cerebral cortex. These results further disproved the involvement of these receptors on astroglial cells in the tonic control of GFAP levels. 5 The binding of [3H]‐idazoxan in the presence of 10−6 m (–)‐adrenaline was used to quantitate in parallel I2‐imidazoline preferring sites in the rat brain after the same treatments. Chronic treatment (7 days) with cirazoline and idazoxan, but not with RX821002, efaroxan or yohimbine, significantly increased (25%) the density of I2‐sites in the cerebral cortex. The up‐regulation of I2‐sites induced by cirazoline was not observed in the liver, a tissue that also expresses I2‐sites but lacks glial cells. 6 A strong correlation (r = 0.97) was found when the mean percentage changes in GFAP immunoreactivity were related to the mean percentage changes in I2 imidazoline sites after the various drug treatments. 7 Together the results suggest a direct physiological function of glial I2‐imidazoline preferring sites in the regulation of GFAP levels.

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