Basal-lateral transport and transcellular flux of methyl alpha-D-glucoside across LLC-PK1 renal epithelial cells.

The characteristics of methyl alpha-D-glucoside transport by the LLC-PK1 cell line are extended by a study of the interaction of this glucose analog with the basal-lateral membrane of these cells: 1 mM methyl alpha-D-glucoside enters LLC-PK1 cells across the basal-lateral membrane 10-times more slowly than when entering across the apical membrane; neither 10 mM glucose nor 10 mM methyl alpha-D-glucoside affect the rate of methyl glucoside uptake at the basal lateral membrane; 0.1 mM phlorizin in the apical hemichamber significantly decreases the rate at which methyl glucoside enter the cell when methyl glucoside is present in the basal-lateral hemichamber; the methyl glucoside transcellular flux ratio, Ja/Jb (apical to basal vs. basal to apical) is 15, whereas Ja/Jb for D-mannitol equals 1; and basal-lateral to apical fluxes (Jb) of mannitol consistently exceed those of methyl glucoside. These results demonstrate that methyl glucoside, unlike glucose, is accumulated within these cells to a high degree because of the limited ability of methyl glucoside to exit the cells by a carrier-mediated pathway. They also raise the important caveat for any studies with glucose (and other low-molecular-weight substrates) by showing that a monosaccharide presented to one surface of these cells will traverse the cell sheet (in part) by the intercellular route and will enter the cell at the unintended cell surface. The ability of the tight junctions of this intercellular route to discriminate between open-chain molecules, such as mannitol, vs. closed ring structures, like methyl glucoside, is also described.