METHYLMERCURY TRANSPORT ACROSS THE BLOOD-BRAIN-BARRIER BY AN AMINO-ACID CARRIER

The mechanism by which methylmercury (MeHg) crosses the blood-brain barrier was examined in the rat. Previous studies demonstrated that intravenous injection of L-cysteine with MeHg accelerates MeHg uptake into brain. Since the complex of MeHg with L-cysteine is structurally similar to L-methionine, a substrate for the L (leucine-preferring) amino acid transport system, this carrier may be involved in MeHg uptake. To examine this hypothesis, the rapid carotid infusion technique was used in the anesthetized rat. The concentration dependence of Hg-203 uptake into brain after injection of MeHg-203-L-cysteine complex was nonlinear, exhibiting characteristics of saturable transport (apparent Michaelis constant 0.39 mM, V(max) 33 nmol.min-1.g-1). A slower, nonsaturable uptake was seen after MeHg-L-cysteine uptake was inhibited by methionine and the amino acid analogue 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), an L system substrate, but not by alpha-methy-laminoisobutyric acid, an alanine-preferring system substrate. Furthermore, L-[C-14]methionine transport was inhibited by MeHg-L-cysteine but not by MeHgCl. There was a significant amount of uptake of Hg-203 when injected as MeHg-203-glutathione and this was inhibited by L-methionine and BCH but not D-methionine. S-ethylglutathione also inhibited Hg-203 uptake after administration as MeHg-203-glutathione but had no effect on MeHg-203-L-cysteine uptake. These results suggest that MeHg may enter the brain as a cysteine complex via the L system and that plasma MeHg-glutathione serves as a source of MeHg-cysteine.