Differential sensitivity of neonatal rat astrocyte cultures to mercuric chloride (MC) and methylmercury (MeHg): studies on K+ and amino acid transport and metallothionein (MT) induction.
Mercuric chloride (MC, Hg2+) and methylmercury (MeHg, CH3Hg+) significantly inhibited the initial rates of uptake of 86Rb (a tracer for K+), as well as the Na(+)-dependent uptake of [3H]-L-glutamate. Both mercury species were also found to increase [3H]-D-aspartate and 86Rb release from cultured astrocytes. Astrocytes were more sensitive to the effects of MC with IC50's for glutamate and Rb uptake an order of magnitude lower than those noted for the organic species (MeHg). Increased potency, and irreversibility relative to MeHg, were also noted for MC induced astrocytic D-aspartate and Rb release. These observations support the hypothesis that the astrocyte plasma membrane is an important target for mercurials and specifically that low concentrations of MC and MeHg inhibit the ability of astrocytes to maintain transmembrane ion gradients. The propensity of MC to interfere with astrocytic functions, relative to MeHg, was also corroborated by measurements on the inducibility of the astrocytic metalloprotein, metallothionein (MT). Whilst a dose-dependent increase in MT protein synthesis occurred upon exposure to either MC or MeHg, MC was shown to be the more potent of the mercurials. The greater susceptibility of astrocytes to MC compared with MeHg lends support, at the cellular level, to the hypothesis that accumulation of inorganic mercury (MC) at an order of magnitude lower concentration than MeHg, may be equally neurotoxic.
Aschner
M
M
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Rising
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Mullaney
K J
KJ
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D008627:Mercuric Chloride / Q000633:toxicity*; D008668:Metallothionein / Q000096:biosynthesis*; D008767:Methylmercury Compounds / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008767:Methylmercury Compounds; D001224:Aspartic Acid; D018698:Glutamic Acid; D008627:Mercuric Chloride; D008668:Metallothionein; D011188:Potassium; C004925:methylmercuric chloride