THE ROLE OF -SH GROUPS IN METHYLMERCURIC CHLORIDE-INDUCED D-ASPARTATEAND RUBIDIUM RELEASE FROM RAT PRIMARY ASTROCYTE CULTURES

Methylmercuric chloride (MeHgCl) was shown to increase D-aspartate and rubidium (Rb; a marker for potassium) release from preloaded astrocyt es in a dose- and time-dependent fashion. Two sulfhydryl (-SH) protect ing agents: a cell membrane non-penetrating compound, reduced glutathi one (GSH), and the membrane permeable dithiothreitol (DTT), were found to inhibit the stimulatory action of MeHgCl on the efflux of radiolab eled D-aspartate as well as Rb. MeHgCl-induced D-aspartate and Rb rele ase was completely inhibited by the addition of 1 mM DTT or GSH during the actual 5 min perfusion period with MeHgCl (10 muM). However, when added after MeHgCl treatment, this inhibition could not be fully sust ained by GSH, while DTT fully inhibited the MeHgCl-induced release Of D-aspartate. Neither DTT or GSH alone had any effect on the rate of as trocytiC D-aspartate release. Accordingly, it is postulated that the s timulatory effect exerted by MeHgCl on astrocytic D-aspartate release is associated with vulnerable -SH groups located within, but not on th e surface of the cell membrane. Omission of Na+ from the perfusion sol ution did not accelerate MeHgCl-induced D-aspartate release, suggestin g that reversal of the D-aspartate carrier cannot be invoked to explai n MeHgCl-induced D-aspartate release. Omission of Ca2+ from the perfus ion solution increased the time-dependent MeHgCl-induced D-aspartate r elease.