Stimulation of D-aspartate efflux by mercuric chloride from rat primary astrocyte cultures.
Mercuric chloride (HgCl2; MC) was shown to increase D-aspartate release from preloaded astrocytes in a dose-dependent fashion. Two sulfhydryl (-SH) protecting agents, a cell membrane non-penetrating compound, reduced glutathione (GSH), and the membrane-permeable dithiothreitol (DTT), were found to inhibit the stimulatory action of MC on the efflux of radiolabeled D-aspartate. MC-induced D-aspartate release was completely inhibited by the addition of 1 mM DTT or GSH during the actual 5 min perfusion period with MC (5 microM). However, when added after MC treatment, 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. Accordingly, it is postulated that the stimulatory effect exerted by MC on astrocytic D-aspartate release is associated with vulnerable -SH groups located within, but not on the surface of the cell membrane. Omission of Na+ from the perfusion solution did not accelerate MC-induced D-aspartate release, suggesting that reversal of the D-aspartate carrier can not be invoked to explain MC-induced D-aspartate release. Furthermore, MC did not appear to be associated with astrocytic swelling.
Mullaney
K J
KJ
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Vitarella
D
D
Albrecht
J
J
Kimelberg
H K
HK
Aschner
M
M
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002840:Chromates / Q000494:pharmacology; D002860:Chromium Radioisotopes; D004229:Dithiothreitol / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D008627:Mercuric Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000494:pharmacology; D013268:Stimulation, Chemical; D013438:Sulfhydryl Compounds / Q000378:metabolism
D002840:Chromates; D002860:Chromium Radioisotopes; D017670:Sodium Compounds; D013438:Sulfhydryl Compounds; D001224:Aspartic Acid; D008627:Mercuric Chloride; C028982:sodium chromate(VI); D005978:Glutathione; D004229:Dithiothreitol