Inhibition of Amino Acid Transport and Protein Synthesis by HgCl 2 and Methylmercury in Astrocytes: Selectivity and Reversibility

The previously reported observation that submi‐cromolar concentrations of HgCl 2 inhibit glutamate uptake reversibly in astrocytes, without effect on 2‐deoxyglucose uptake, suggested that elemental mercury vapor, which is oxidized to mercuric mercury in the brain, might cause neurodegenerative change through the mediation of glutamate excitotoxicity. Here, selectivity is explored further by measuring the inhibition of other amino acid transporters and protein synthesis as a function of HgCl 2 concentration. The properties of MeHgCl were compared under identical conditions, and some morphological correlates of function were examined. Inhibition of amino acid transport by HgCl 2 was selective, whereas MeHgCl was nonselective. The 50% inhibitory concentrations of HgCl 2 for uptake of α‐aminoiso‐butyric acid by system A, uptake of α‐aminoisobutyric acid or kynurenine by a system L variant, and uptake of γ‐ami‐nobutyric acid were all two‐ to fourfold greater than that for uptake of glutamate. The submicromolar concentrations of HgCl 2 that inhibited glutamate transport also inhibited protein synthesis, but in a rapidly reversible fashion, and elicited only discrete ultrastructural changes (heterochromatin. increased numbers of lysosomal bodies, and increased complexity of cell surface). In contrast, inhibition of protein synthesis by MeHgCl was acutely (1‐h) irreversible and became marked only at concentrations higher than those that elicited gross morphologic change in the form of “bleb”‐like swellings. The results lend support to the proposed excitotoxic mediation of mercury vapor neurotoxicity and reveal a sharp contrast between the effects of HgCl 2 and MeHgCl on astrocytes.