STIMULATION OF D-ASPARTATE EFFLUX BY MERCURIC-CHLORIDE FROM RAT PRIMARY ASTROCYTE CULTURES

Mercuric chloride (HgCl2; MC) was shown to increase D-aspartate releas e from preloaded astrocytes in a dose-dependent fashion. Two sulfhydry l (-SH) protecting agents, a cell membrane non-penetrating compound, r educed glutathione (GSH), and the membrane-permeable dithiothreitol (D TT), were found to inhibit the stimulatory action of MC on the efflux of radiolabeled D-aspartate. MC-induced D-aspartate release was comple tely inhibited by the addition of 1 mM DTT or GSH during the actual 5 min perfusion period with MC (5 muM). However, when added after MC tre atment, this inhibition could not be sustained by GSH, while DTT fully inhibited the MC-induced release of D-aspartate. Neither DTT nor GSH alone had any effect on the rate of astroCYtiC D-aspartate release. Ac cordingly, it is postulated that the stimulatory effect exerted by MC on astrocytic D-aspartate release is associated with vulnerable -SH gr oups located within, but not on the surface of the cell membrane. Omis sion of Na+ from the perfusion solution did not accelerate MC-induced D-aspartate release, suggesting that reversal of the D-aspartate carri er can not be invoked to explain MC-induced D-aspartate release. Furth ermore, MC did not appear to be associated with astrocytic swelling.