Abstract
The cotransport of sodium and glutamate by system X(AG)- is believed to be coupled to the countertransport of potassium and hydroxyl ion equivalents. Accordingly, the uptake of glutamate or D-aspartate in astrocytes is accompanied by an intracellular acidification. Here, we report that HgCl2 blocks the glutamate-induced acidification with an approximate 50% inhibitor concentration (IC50) of 55 nM, an order of magnitude below its IC50 for inhibition of glutamate uptake. At 100 nM HgCl2, glutamate-induced acidification was abolished, whereas glutamate uptake was unaffected. D-Aspartate-induced acidification was equally sensitive to HgCl2, indicating that HgCl2 blocked a transporter-mediated, rather than a receptor-mediated, acidification. Unaltered responses to acute acid and alkaline loads showed that HgCl2 was not acting indirectly via a change in pH regulation. We conclude that HgCl2 acted directly on the glutamate transporter to uncouple the uptake of glutamate from the export of hydroxyl equivalents. In contrast, two other sulfhydryl reagents, p-chloromercuribenzensulfonate and N-ethylmaleimide, failed to discriminate between glutamate-induced acidification and glutamate uptake. An additional effect of > or = 100 nM HgCl2, i...Continue Reading
References
Dec 1, 1977·Journal of Neurochemistry·A SchousboeL Hertz
Dec 4, 1992·Toxicology·N Brookes
Dec 3, 1992·Nature·M BouvierD Attwell
Aug 14, 1992·Biochimica Et Biophysica Acta·P R van IwaardenW N Konings
Jan 1, 1990·Progress in Neurobiology·M Chesler
Feb 1, 1985·Journal of Neurochemistry·N Brookes, P J Yarowsky
Oct 1, 1989·Journal of Neurochemistry·N Brookes, D A Kristt
Jan 1, 1985·Journal of Neurochemistry·G J McBean, P J Roberts
Apr 1, 1988·Journal of Neurochemistry·N Brookes
Sep 29, 1988·Nature·B BarbourD Attwell
Jan 10, 1985·Biochimica Et Biophysica Acta·S GrinsteinA Rothstein
Nov 23, 1982·Biochemistry·B I Kanner, A Bendahan
Nov 8, 1983·Biochemistry·P J NelsonG Rudnick
Sep 3, 1984·Biochimica Et Biophysica Acta·H N Christensen
Dec 1, 1993·Journal of Neurochemistry·M B RobinsonJ R Buchhalter
Mar 24, 1995·Neuroscience Letters·K KondoA Baba
Mar 24, 1995·The Journal of Biological Chemistry·N ZerangueM P Kavanaugh
Jun 28, 1993·FEBS Letters·B I Kanner
Jun 1, 1993·Current Opinion in Neurobiology·S G Amara, J L Arriza
Sep 17, 1993·Neuroscience Letters·N Brookes, R J Turner
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J D RothsteinR W Kuncl
Jan 1, 1996·Journal of Neurochemistry·M G JuddN Brookes
Citations
Dec 6, 2005·Biological & Pharmaceutical Bulletin·Tatsumi Adachi, Manabu Kunimoto
Jun 3, 1998·NMR in Biomedicine·J PfeufferD Leibfritz
Sep 30, 2006·The Journal of Physiology·Simen Gylterud OweDavid Attwell
May 12, 1998·The American Journal of Physiology·T N Nagaraja, N Brookes
May 23, 2001·Progress in Neurobiology·N C Danbolt
Mar 22, 2001·Toxicology in Vitro : an International Journal Published in Association with BIBRA·T A Toimela, H Tähti
Apr 23, 2005·Toxicology and Applied Pharmacology·Vanessa A Fitsanakis, Michael Aschner