EVIDENCE FOR TRANSCAPILLARY TRANSPORT OF REDUCED GLUTATHIONE IN VASCULAR PERFUSED GUINEA-PIG BRAIN

Using a vascular brain perfusion model in the guinea-pig, the net upta ke of [S-35]-GSH by the brain was found to be linear and similar in va rious regions during 10 min perfusion. Dual labeled [S-35 and H-3] GSH taken up by the brain had the same isotope ratio as the injected stoc k whether or not gamma- glutamyl transferase was inhibited. Greater th an 96% of brain uptake of [S-35]-cysteine-labeled GSH and [H-3]-glycin e-labeled GSH were in intact form. Transcytosis of [S-35]-GSH from lum en into brain parenchyma was demonstrated using a capillary depletion technique. Both GSH and GSH-monoethyl ester inhibited [S-35]-GSH trans port. Thus, we have demonstrated blood-brain barrier extraction of cir culating GSH in a brain perfusion model, and the transcytosis of intac t GSH into the brain parenchyma without breakdown. (C) 1994 Academic P ress, Inc.