OSMOTIC REGULATION OF NA-MYO-INOSITOL COTRANSPORTER MESSENGER-RNA LEVEL AND ACTIVITY IN ENDOTHELIAL AND NEURAL CELLS

Myo-inositol (MI) is an important factor in the synthesis of phosphoin ositides, and, as an osmolyte, MI contributes to the regulation of cel l volume. In cells of renal origin, hypertonicity causes an increase i n sodium-dependent MI transporter (SMIT) mRNA levels and MI transport. However, it is unknown whether changes in osmolarity regulate transpo rt of MI in neural or endothelial cells. In these studies, neural and endothelial cells were exposed to hyperosmotic medium for up to 48 h, and the effect on MI transport was determined. Transport of MI was max imally increased by exposing the cells to hyperosmotic medium for 24 h . Kinetic analysis of high-affinity MI transport demonstrated an incre ase in the apparent maximal velocity with no significant change in the apparent K-m. The hyperosmotic induction of MI transport was blocked by the addition of cycloheximide, indicating a requirement for protein synthesis, and was associated with increased levels of SMIT mRNA. In contrast to the effect of hypertonicity, exposure of neural and endoth elial cells to hypotonic conditions caused a decrease in SMIT mRNA lev els and MI transport in endothelial cells. These studies demonstrate t hat, in extrarenal cell types, changes in osmolarity also regulate SMI T activity and mRNA levels.