Selective inhibition of glutamate uptake by mercury in cultured mouse astrocytes.
We studied the effects of organic and inorganic mercury (Hg) on the uptake of L-[3H] glutamate (L-GLU) in cultured mouse astrocytes. Following exposure to mercuric chloride (MC) [0.2 approximately 5.0 microM], selective and dose-dependent inhibition of L-GLU uptake to 50% of control levels was observed, whereas 2-deoxyglucose (2-DG) uptake was not significantly affected. Methylmercuric chloride (MMC) also inhibited L-GLU uptake but 50% reduction was reached only at a concentration of 10 microM. Inhibition of L-GLU uptake by MMC appears to be closely linked to voltage-sensitive calcium channels as evidenced by the lack of L-GLU uptake inhibition by MMC in calcium-free medium or in the presence of the channel blocker verapamil. Exposure to a variety of divalent metallic ions, including CuCl2, FeCl2 and ZnCl2, did not affect L-GLU uptake in astrocytes in vitro. Exposure to PbCl2, however, resulted in a decline in L-GLU uptake, though to a much smaller degree than that observed with Hg compounds. Selective impairment of astroglial L-GLU transport may represent a critical early pathogenetic feature of Hg-induced neurotoxicity.
Kim
P
P
Department of Pathology, University of California, Irvine 92717, USA.
Choi
B H
BH
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D008628:Mercury / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL
D018698:Glutamic Acid; D008628:Mercury