Mechanisms of methylmercury transport across the blood-brain barrier

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1993

OSTI ID:5146036

Kerper, L E

Methylmercury readily enters the brain of exposed individuals, and is highly neurotoxic. The goal of this research was to determine the mechanisms of methylmercury transport across both the luminal and abluminal membranes of brain capillary endothelial cells, the cells which comprise the blood-brain barrier. The rapid carotid injection technique was used in rats to investigate the uptake of methylmercury from blood into brain endothelial cells. Uptake of ([sup 203]Hg)-methylmercury complexed with L-cysteine (CH[sub 3] [sup 203]Hg-L-Cys) was more rapid than that of ([sup 203]Hg)-methylmercury complexed with D-cysteine or bovine serum albumin. Uptake of CH[sub 3][sup 203]Hg-L-Cys was saturable, and was inhibited by substrates for the L (alanine-preferring) carrier. Brain uptake of [sup 14]C-L-methionine was inhibited by CH[sub 3]Hg-L-Cys but not by CH[sub 3]HgCl. Uptake of [sup 203]Hg administered as CH[sub 3]Hg-L-Cys-glutathione (CH[sub 3][sup 203]Hg-GSH) was comparable to CH[sub 3][sup 203]Hg-L-Cys uptake at 2 [mu]M. L-Methionine and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) inhibited [sup 203]Hg uptake administered as CH[sub 3][sup 203]Hg-GSH, whereas acivicin had no effect. This uptake was also inhibited by S-ethylglutathione when pH of the injection solution was allowed to rise to 8.5. In later experiments performed at pH 8.2, uptake of [sup 203]Hg administered as CH[sub 3][sup 203]Hg-GSH was inhibited only by BCH. To study mechanisms of methylmercury efflux from endothelial cells, a primary culture of bovine brain capillary endothelial cells was developed. Intracellular glutathione concentration was 2.6 [+-] 0.7 mM. Incubation of CH[sub 3][sup 203]HgCl-preloaded cells with GSH depletors decreased ([sup 203]Hg)-methylmercury efflux in a dose-dependent manner which correlated with intracellular GSH concentrations. ([sup 203]Hg)-Methylmercury efflux was also inhibited by GSH-S-conjugates an GSH analogs, but not by amino acids.

• Research Organization: Rochester Univ., NY (United States)
• OSTI ID: 5146036
• Country of Publication: United States
• Language: English

Related Subjects

551000 -- Physiological Systems
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL PATHWAYS
BLOOD-BRAIN BARRIER
METHYLMERCURY
ORGANIC COMPOUNDS
ORGANIC MERCURY COMPOUNDS
STRUCTURE-ACTIVITY RELATIONSHIPS
TOXICITY
UPTAKE