RAPID ENHANCEMENT OF HIGH-AFFINITY GLUTAMATE UPTAKE BY GLUCOCORTICOIDS IN RAT CEREBRAL-CORTEX SYNAPTOSOMES AND HUMAN NEUROBLASTOMA CLONE SK-N-SH - POSSIBLE INVOLVEMENT OF G-PROTEIN

The rapid effects of glucocorticoids(GCs) on the Na+-dependent, high a ffinity uptake of (3)[H]-L-glutamate(Glu) in rat cerebral cortex synap tosomes(4 min incubation) and human neuroblastoma clone SK-N-SH (10 mi n preincubation and 5 min incubation) were investigated. GCs, includin g corticosterone, corticosterone-sulfate, hydrocortisone-hemisuccinate and dexamethasone 21-phosphate(DEX) were found stimulating Glu uptake . The uptakes in synaptosomes and SK-N-SH cells were increased to 117- 126% and 121-137% respectively of the control by 10(-6) mol/L GCs, The stimulation of GCs was dose-dependent. The maximal effect of DEX in S K-N-SH cells appeared at 10(-7) mol/L, and the least effective dose of DEX was at 10(-9) mol/L. Guanosine 5-O-(2-thiodiphosphate), an inhibi tor of G-protein activation, could block the stimulation of GCs. The r esults indicated that GCs rapidly enhance the Na+-dependent high affin ity Glu uptake in nerve endings and SK-N-SH cells, even at the concent ration of physiological conditions, and the G-protein on synaptic memb ranes or SK-N-SH cell membranes might be involved in the effect of GCs . (C) 1998 Academic Press.