Specificity and Reversibility of the Inhibition by HgCl₂ of Glutamate Transport in Astrocyte Cultures

Abstract

Inhibition of glutamate transport is a potential indirect cause of excitotoxic damage by glutamate in the CNS. The mercuric ion, the form in which metallic mercury vapor is believed to exert its neurotoxic action, is a known inhibitor of amino acid transport. This study examines the specificity with which HgCl2 inhibits glutamate transport in mouse cerebral astrocytes by means of comparative measurements of 2-deoxyglucose uptake. Uptake of 2-deoxyglucose is an index of glucose utilization that reflects the function of Na+,K+-ATPase and hexokinase, and is sensitive to Na+ entry. The kinetic parameters, ionic dependence, and substrate specificity of glutamate transport in these astrocyte cultures were consistent with the commonly occurring system designated X-AG. Acute exposure to 0.5 microM HgCl2 inhibited by 50% the initial rate of glutamate transport but did not affect 2-deoxyglucose uptake. Glutamate transport was not detectably inhibited by Al2+, Pb2+, Co2+, Sr2+, Cd2+, or Zn2+ (10 microM as chlorides). The inhibitory action of 0.5 microM HgCl2 on glutamate transport was rapidly reversible. The action of 1-2 microM HgCl2 was progressive when exposures were extended to 1-3 h, and was more slowly reversible. These results suggest that Hg2+ can impair glial glutamate transport reversibly at exposure levels that do not compromise some other vital cell functions.

Mercury-stimulated histamine uptake and binding in cultured astroglial and cerebral endothelial cells

“…1). Over a wide range of concentration, organic and inorganic mercurials were found exclusively inhibitory for glial glutamate uptake (Brookes, 1988;Aschner et al, 1990Aschner et al, , 1993. This indicates marked differences in glutamate and histamine uptake systems especially in the structure of carrier proteins.…”

Acute Cytotoxic Effects of Mercuric Compounds in Cultured Astrocytes Prepared from Cerebral Hemisphere and Cerebellum of Newborn Rats

“…8) Interestingly, both MeHg and Hg 2+ converted from MeHg accumulate preferentially in astrocytes rather than in neurons, 1,[9][10][11] whereas Hg 2+ is generally seen in neurons after exposure to mercuric chloride or Hg 0 vapor. 12,13) Since glutamate uptake in cultured astrocytes is also inhibited by Hg 2ϩ , 2,14,15) an astrocyte dysfunction induced by Hg 2ϩ may also indirectly contribute MeHg neurotoxicity.…”

In Vivo Effects of Inorganic Mercury (HgCl2) on Striatal Dopaminergic System

“…HgCl exerts a well-known inhibitory e!ect on membrane transport that is generally attributed to its high-a$nity interaction with protein sulfydryl groups (Bondy et al, 1979). For example, submicromolar concentrations of HgCl have been found to inhibit selectively glutamate uptake in mouse astrocytes (Brookes, 1988;Brookes and Kristt, 1989). Freitas et al (1996) reported that both organic mercury and inorganic mercury inhibit Ca>-ATPase and Ca> uptake by brain microsomes with the inhibitory potency of inorganic mercury being higher than that of organic mercury, probably re#ecting di!erences in the a$nity for the sulfydryl groups of the mercury compounds.…”