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 (10min 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 at10(-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.
Zhu
B G
BG
Institute of Neuroscience, Second Military Medical University, Shanghai, 200433, China.
Zhu
D H
DH
Chen
Y Z
YZ
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D018698:Glutamic Acid; D003907:Dexamethasone; D019204:GTP-Binding Proteins; D003345:Corticosterone