The role of -SH groups in methylmercuric chloride-induced D-aspartate and 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 astrocytes in a dose- and time-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 MeHgCl on the efflux of radiolabeled D-aspartate as well as Rb. MeHgCl-induced D-aspartate and Rb release was completely inhibited by the addition of 1 mM DTT or GSH during the actual 5 min perfusion period with MeHgCl (10 microM). However, when added after MeHgCl treatment, this inhibition could not be fully sustained 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 astrocytic D-aspartate release. Accordingly, it is postulated that the stimulatory effect exerted by MeHgCl 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 MeHgCl-induced D-aspartate release, suggesting that reversal of the D-aspartate carrier cannot be invoked to explain MeHgCl-induced D-aspartate release. Omission of Ca2+ from the perfusion solution increased the time-dependent MeHgCl-induced D-aspartate release.
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
K J
KJ
Mullaney
M N
MN
Fehm
D
D
Vitarella
D E
DE
Wagoner
M
M
Aschner
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000493:pharmacokinetics*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D008767:Methylmercury Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000493:pharmacokinetics*; D012414:Rubidium Radioisotopes; D013438:Sulfhydryl Compounds / Q000502:physiology*
D008767:Methylmercury Compounds; D012414:Rubidium Radioisotopes; D013438:Sulfhydryl Compounds; D001224:Aspartic Acid; D012413:Rubidium; C004925:methylmercuric chloride