Uptake of methylmercury in the rat brain: effects of amino acids.
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 less than 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 (alpha S, 5S-alpha-amino-3-chloro-4,5-dihydro-5-isoxazolacetic acid), an irreversible inhibitor of gamma-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.
Aschner
M
M
Environmental Health Sciences Center, University of Rochester, School of Medicine and Dentistry, NY 14642.
Clarkson
T W
TW
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008767:Methylmercury Compounds / Q000493:pharmacokinetics*; D051381:Rats; D013395:Sucrose / Q000493:pharmacokinetics
D000596:Amino Acids; D008767:Methylmercury Compounds; D013395:Sucrose