myo-Inositol uptake by culture neuroblastoma cells at a concentration of myo-inositol less than 50 microM was largely Na+ dependent. Exposing neuroblastoma cells to media supplemented with increasing concentrations of myo-inositol resulted in an increase in myo-inositol accumulation and intracellular content, but myo-inositol incorporation into phospholipids was not increased. The data indicate that myo-inositol exists as separate pools in neuroblastoma cells, and one or more of these pools may contribute to phospholipid synthesis. Exposing neuroblastoma cells to an increased concentration of glucose caused a decrease in myo-inositol uptake by two separate mechanisms. Acute exposure of the cells to 30 mM glucose caused a myo-inositol concentration-dependent decrease in Na(+)-dependent myo-inositol uptake. We propose that the acute inhibition of myo-inositol uptake by glucose is likely due to a competitive type of inhibition. Chronic exposure of cells to media containing 30 mM glucose or 30 mM galactose also caused decreases in myo-inositol uptake and incorporation into inositol phospholipids and intracellular myo-inositol content. This decrease in myo-inositol metabolism persisted at a higher concentration of external myo-inositol than the acute inhibition. Supplementing media containing 30 mM glucose or 30 mM galactose with 250 microM myo-inositol restored myo-inositol metabolism and content. The inhibition of myo-inositol uptake by cells chronically exposed to increased concentrations of glucose or galactose was due to a noncompetitive type of inhibition that was blocked by the addition of sorbinil. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose or 30 mM galactose caused a decrease in Na(+)-K(+)-ATPase transport activity and resting membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)