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Na + ‐Dependent and Phlorizin‐Inhibitable Transport of Glucose and Cycasin in Brain Endothelial Cells
Author(s) -
Matsuoka Toshiyuki,
Nishizaki Tomoyuki,
Kisby Glen E.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020772.x
Subject(s) - phlorizin , glucose transporter , blood–brain barrier , extracellular , chemistry , biochemistry , endothelial stem cell , biophysics , transporter , neurodegeneration , glucose uptake , microbiology and biotechnology , biology , medicine , endocrinology , central nervous system , in vitro , insulin , disease , gene
Although cycasin (methylazoxymethanol β‐ d ‐glucoside) is proposed to be a significant etiological factor for the prototypical neurodegenerative disorder Western Pacific amyotrophic lateral sclerosis and parkinsonism‐dementia complex, the mechanism underlying transport of cycasin across the blood‐brain barrier (BBB) is unknown. We examined cycasin transport in cultured bovine brain endothelial cells, a major element of the BBB. Cycasin was taken up into endothelial cells in a dose‐dependent manner with maximal uptake observed at a concentration of 10 µ M . Cycasin uptake was significantly inhibited by α‐methyl‐ d ‐glucoside, a specific analogue for the Na + ‐dependent glucose transporter (SGLT), by the SGLT inhibitor phlorizin, by replacement of extracellular NaCl with LiCl, and by dinitrophenol (DNP), an inhibitor of energy metabolism. In addition, cycasin produced inward currents in a whole‐cell voltage clamp configuration. Peak currents were observed at 10 µ M with a trend toward reduction at higher concentrations, and currents were clearly blocked by α‐methyl‐ d ‐glucoside, phlorizin, and DNP. In addition, cycasin never evoked currents in Na + ‐free extracellular solution. These results suggest that cycasin is selectively transported across brain endothelial cells, possibly across the BBB by a Na + /energy‐dependent glucose transporter.