EFFECT OF DIBUTYRYL-CYCLIC-AMP AND DEXAMETHASONE ON GLUTAMINE-SYNTHETASE GENE-EXPRESSION IN RAT ASTROCYTES IN CULTURE

Astrocytes are the primary site of glutamate conversion to glutamine i n the brain. We examined the effects of treatment with either dibutyry l cyclic AMP and/or the synthetic glucocorticoid dexamethasone on glut amine synthetase enzyme activity and steady-state mRNA levels in cultu red neonatal rat astrocytes. Treatment of cultures with dibutyryl cycl ic AMP alone (0.25 mM-1.0 mM) increased glutamine synthetase activity and steady state mRNA levels in a dose-dependent manner. Similarly, tr eatment with dexamethasone alone (10(-7)-10(-5) M) increased glutamine synthetase mRNA levels and enzyme activity. When astrocytes were trea ted with both effecters, additive increases in glutamine synthetase ac tivity and mRNA were obtained. However, the additive effects were obse rved only when the effect of dibutyryl cyclic AMP alone was not maxima l. These findings suggest that the actions of these effecters are medi ated at the level of mRNA accumulation. The induction of glutamine syn thetase mRNA by dibutyryl cyclic AMP was dependent on protein synthesi s while the dexamethasone effect was not. Glucocorticoids and cyclic A MP are known to exert their effects on gene expression by different mo lecular mechanisms. Possible crosstalk between these effector pathways may occur in regulation of astrocyte glutamine synthetase expression.