Uptake of methylmercury in the rat brain: effects of amino acids

Abstract

Aspects of the regulation of methylmercury (MeHg) transport across the blood-brain barrier (BBB) were investigated in the in vivo Long-Evans female rat. Fifteen s after intracarotid injection, brain 203Hg concentration was significantly increased in animals injected with 0.05 mM [ 203Hg]MeHgCl plus 0.1 mM l-cysteine compared with controls ( P < 0.05). This l-cysteine-enhanced 203Hg brain uptake was abolished by coinjections of [ 203Hg]MeHgCl with 0.1 mM l-cysteine- l-methionine, or 0.1 mM l-cysteine plus AT-125 (α S, 5S-α-amino-3-chloro-4,5-dihydro-5-isoxazolacetic acid), an irreversible inhibitor of γ-glutamyl transpeptidase. Coinjections of rats with [ 203Hg]MeHgCl and 0.1 mM d-cysteine did not result in an increase in the rate of 203Hg uptake compared with controls. Furthermore, [ 203Hg]MeHg uptake at 15 s after intracarotid injections in the rat was stereospecific to the neutral amino acid carrier, as 203Hg uptake across the BBB was not inhibited by coinjections of [ 203Hg]MeHgCl with aspartic acid, an acidic amino acid. These results indicate the presence in brain capillaries of a transport system capable of selectively mediating MeHg uptake across the brain capillary endothelial cell membrane.