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.
Ioannou
Nektaria
N
Laboratory of Biological Chemistry, Medical School, University of Athens, Mikras Asias 75, GR 11527 Athens, Greece.
Liapi
Charis
C
Sekeris
Constantine E
CE
Palaiologos
George
G
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D003609:Dactinomycin; D015735:Mifepristone; D018698:Glutamic Acid; D003907:Dexamethasone; D008274:Magnesium; D011188:Potassium; D002118:Calcium