Effects of Dexamethasone and DHEA on the Changes of Glutamate and Polyamine Uptake in Rat Astrocytes by Lipopolysaccharide and Antimycin A

Effects of Dexamethasone and DHEA on the Changes of Glutamate and Polyamine Uptake in Rat Astrocytes by Lipopolysaccharide and Antimycin A

<P> Interactions among dexamethasone, dehydroepiandrosterone (DHEA), lipopolysaccharide (LPS), and antimycin A on the glutamate uptake and the polyamine uptake were investigated in primary cultures of rat cerebral cortical astrocytes to examine the effects of dexamethasone and DHEA on the regulatory role of astrocytes in conditions of increased extracellular concentrations of glutamate or polyamines. 1. [<SUP>3</SUP>H]Glutamate uptake: LPS and antimycin A decreased <I>V</I><SUB>max</SUB>, but both drugs had little effect on <I>K</I><SUB>m</SUB>. Dexamethasone also decreased basal <I>V</I><SUB>max</SUB> without any significant effect on <I>K</I><SUB>m</SUB>. And dexamethasone further decreased the antimycin A-induced decrease of <I>V</I><SUB>max</SUB>. DHEA did not affect the kinetics of basal glutamate uptake and the change by LPS or antimycin A. 2. [<SUP>14</SUP>C]Putrescine uptake: LPS increased <I>V</I><SUB>max</SUB>, and antimycin A decreased <I>V</I><SUB>max</SUB>. They showed little effect on <I>K</I><SUB>m</SUB>. Dexamethasone decreased <I>V</I><SUB>max</SUB> of basal uptake and further decreased the antimycin A-induced decrease of <I>V</I><SUB>max</SUB>, and also decreased <I>V</I><SUB>max</SUB> to less than control in LPS-treated astrocytes. DHEA did not affect <I>K</I><SUB>m</SUB> and the change of <I>V</I><SUB>max</SUB> by LPS or antimycin A. 3. [<SUP>14</SUP>C]Spermine uptake: Antimycin A decreased <I>V</I><SUB>max</SUB>, and LPS might increase <I>V</I><SUB>max</SUB>. <I>K</I><SUB>m</SUB> was little affected by the drugs. Dexamethasone decreased basal <I>V</I><SUB>max</SUB> and might further decrease the antimycin A-induced decrease of <I>V</I><SUB>max</SUB>. And dexamethasone also decreased <I>V</I><SUB>max</SUB> to less than control in LPS-treated astrocytes. DHEA might increase basal <I>V</I><SUB>max</SUB> and <I>V</I><SUB>max</SUB> of LPS-treated astrocytes. 4. <I>V</I><SUB>max</SUB> of glutamate uptake by astrocytes was increased by putrescine (1000 μM &amp; 2000 μM) and spermidine (200 μM, 500 μM &amp; 2000 μM). Spermine, 200 μM (and 100 μM), also increased <I>V</I><SUB>max</SUB>, but a higher dose of 2000 μM decreased <I>V</I><SUB>max</SUB>. <I>K</I><SUB>m</SUB> of glutamate uptake was not significantly changed by these polyamines, except that higher doses of spermine showed tendency to decrease <I>K</I><SUB>m</SUB> of glutamate uptake. In astrocytes, dexamethasone inhibited the glutamate uptake and the polyamine uptake in normal or hypoxic conditions, and the polyamine uptake might be stimulated by LPS and DHEA. Polyamines could aid astrocytes to uptake glutamate.