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 affinity uptake of (3)[H]-L-glutamate(Glu) in rat cerebral cortex synaptosomes(4 min incubation) and human neuroblastoma clone SK-N-SH (10 min preincubation and 5 min incubation) were investigated. GCs, including 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 SK-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 inhibitor of G-protein activation, could block the stimulation of GCs. The results indicated that GCs rapidly enhance the Na+-dependent high affinity Glu uptake in nerve endings and SK-N-SH cells, even at the concentration of physiological conditions, and the G-protein on synaptic membranes or SK-N-SH cell membranes might be involved in the effect of GCs. (C) 1998 Academic Press.