Methyl mercury uptake across bovine brain capillary endothelial cells in vitro: the role of amino acids.
Previous studies in the rat in vivo have demonstrated that co-injection of methyl mercury (MeHg) with L-cysteine into the common carotid artery enhances brain Hg levels following a single capillary pass through the CNS vasculature. In order to elucidate the relationship between MeHg transport and the neutral amino acid transport carrier system, regulatory aspects of MeHg transport across the bovine blood-brain barrier were investigated in isolated brain microvessel preparations. Following 1 hour co-incubations of 203Hg-MeHgCl with 0.1 mM L-cysteine at 37 degrees, 203Hg uptake by suspended microvessels was significantly increased (P less than 0.05) compared with controls. This enhanced capillary uptake of 203Hg was abolished by co-incubations of microvessels 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. One hr co-incubations of bovine capillaries with 203Hg-MeHgCl and 0.1 mM D-cysteine at 37 degrees or 0.1 mM L-cysteine at 0 degrees did not increase rat of 203Hg uptake compare with controls. These results indicate that L-cysteine enhances the rate of capillary MeHg uptake. The accumulation of 203Hg in the bovine microvessels appears to be a carrier-mediated process. It is inhibited by L-methionine, a competitive substrate for neutral amino acid transport, and by AT-125. Capillary uptake of 203Hg is stereospecific to the L-enantiomorph of cysteine, suggesting selective uptake of MeHg across the blold-brain barrier. The data emphasize the relationship between the L-enantiomorph neutral amino acid carrier system and MeHg transport across the capillaries.
Aschner
M
M
Environmental Health Sciences Center, University of Rochester, School of Medicine and Dentistry, New York 14642.
Clarkson
T W
TW
D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D003545:Cysteine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism; D066298:In Vitro Techniques; D008631:Mercury Radioisotopes; D008767:Methylmercury Compounds / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism
D000596:Amino Acids; D008631:Mercury Radioisotopes; D008767:Methylmercury Compounds; D013395:Sucrose; D005169:Factor VIII; D003545:Cysteine