Effects of dexamethasone on K(+)-evoked glutamate release from rat hippocampal slices.

Dexamethasone (DEX) at physiologically elevated (stress) concentration (1 microM) decreased K(+)-evoked glutamate release from rat hippocampal slices under superfusion in the presence of Ca2+. On the contrary 10 microM DEX increased this K(+)-evoked glutamate release while 0.1 microM DEX had no effect. The glucocorticoid antagonist for the "classic" receptor, RU 486, completely reversed the effect of 1 microM DEX. Actinomycin D had no effect. Dexamethasone at 1 microM had no effect on the Ca2(+)-independent (10 mM Mg2+ replacing 1 mM Ca2+) K(+)-evoked glutamate release. Dexamethasone at 1 microM or 10 microM had no effect on the phosphate-activated glutaminase--the key enzyme for the biosynthesis of neurotransmitter glutamate. These results suggest that the effect of DEX on K(+)-evoked glutamate release: (i) depends on its concentration; (ii) is exerted on the Ca2(+)-dependent (neurotransmitter release), at least at physiological stress concentrations; and (iii) is exerted via the classical receptor but is nongenomic.