Brain uptake, retention, and efflux of aluminum and manganese.

作者: Robert A Yokel

DOI: 10.1289/EHP.02110S5699

关键词: Monocarboxylate transporterBlood–brain barrierExtracellular fluidBiochemistryOrganic anion transporter 1ChemistryEffluxMicrodialysisBand 3Transferrin

摘要: My colleagues and I investigated the sites mechanisms of aluminum (Al) manganese (Mn) distribution through blood-brain barrier (BBB). Microdialysis was used to sample non-protein-bound Al in extracellular fluid (ECF) blood (plasma) brain. Brain ECF appearance after intravenous citrate injection too rapid attribute diffusion or transferrin-receptor-mediated endocytosis, suggesting another carrier-mediated process. The brain:blood concentration ratio 0.15 at constant brain concentrations, efflux. Pharmacological manipulations suggested efflux carrier might be a monocarboxylate transporter (MCT). However, lack (14)C-citrate uptake into rat erythrocytes it is not good substrate for isoform MCT1 band 3 anion exchanger. murine-derived endothelial cells appeared mediated, Na independent, pH energy dependent. Uptake inhibited by substrate/inhibitors MCT organic families. Determination (26)Al various times prolonged half-life. It appears that transferrin cross BBB different mechanisms, much entering rapidly effluxed, probably as citrate, but some retained quite time. influx Mn(2+) ion Mn determined with situ perfusion technique, greater than attributable diffusion, uptake. approximately 3-fold ion, primary species After brain, more predicted from diffusion. permeation mediated carriers may help regulate their concentrations.

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