Methyl Mercury Uptake Across Bovine Brain Capillary Endothelial Cells in Vitro: The Role of Amino Acids
Abstract
Abstract: 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°, 203Hg uptake by suspended microvessels was significantly increased (P<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 gammaglutamyl‐transpeptidase. One hr co‐incubations of bovine capillaries with 203Hg‐MeHgCl and 0.1 mM D‐cysteine at 37° or 0.1 mM L‐cysteine at 0° did not increase rat of 203Hg uptake compared 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.
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