Arachidonic acid, a major polyunsaturated fatty acid of membrane phospholipids in the CNS, reduced the high-affinity uptake of glutamate and gamma-aminobutyric acid (GABA) in both rat brain cortical slices and synaptosomes. alpha-Aminoisobutyric acid uptake was not affected. Intrasynaptosomal sodium was increased concomitant with decreased (Na+ + K+)-ATPase activity in synaptosomal membranes. The reduction of GABA uptake in synaptosomes could be partially reversed by alpha-tocopherol. The inhibition of membrane-bound (Na+ + K+)-ATPase by arachidonic acid was not due to a simple detergent-like action on membranes, since sodium dodecyl sulfate stimulated the sodium pump activity in synaptosomes. These data indicate that arachidonic acid selectively modifies membrane stability and integrity associated with reductions of GABA and glutamate uptake and of (Na+ + K+)-ATPase activity.
The intracellular volume of neoplastic brain cells was investigated with regard to the effects of hypo-osmolality and hyperosmolality utilizing double isotopic labeling with 3-0-methyl-D-glucose or tritiated water to measure the total volume of the pellet and inulin or polyethyleneglycol to measure the extracellular volume of the pellet. The cellular pellets were rapidly separated from the incubation medium by centrifugation after addition of an oil mixture. After 60 minutes incubation in Hanks balanced salt medium, the intracellular volume was 7.50 +/- 0.64, 8.48 +/- 0.19, and 2.97 +/- 0.18 ml H2O per 10(6) packed cells for C-6 glioma cells, N18TG-2 neuroblastoma cells, and NG108-15 neuroblastoma X glioma hybrid cells, respectively. The extracellular trapped space of these cultured cells was about one third of the intracellular volume. The intracellular volume of C-6 glioma cells was increased in hypotonic environment, whereas it was decreased with hyperosmolality. Both intracellular sodium and potassium were increased with increased osmolality of the incubation media. These data indicate iso-osmotic regulation by tumor cells, i.e., there is a good correlation between the intracellular volume, intracellular cations and lactate levels of C-6 glioma cells under various osmotic conditions.
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