title: Osmoregulatory changes in myo-inositol content and Na+/myo-inositol cotransport in rat cortical astrocytes.
abstract: Exposure of cortical astrocytes to 325, 350, or 390 mosM culture media for 48 h caused a 1.4-, 2.1-, and 3.5-fold increase, respectively, in cellular content of the compatible osmolyte myo-inositol. Elevated myo-inositol levels accounted for approximately 56-100% of the solute needed by the cells for complete volume regulation under hypertonic conditions. Myo-inositol accumulation was associated with 4-5-fold (peak rate) and 1.8-2-fold (steady-state rate) increases in the rate of Na(+)-dependent myo-inositol uptake when cells were acclimated to 390 mosM culture medium for 12 h or 24-96 h, respectively. When medium osmolality was elevated by 25 mosM, peak and steady-state increases in myo-inositol uptake of 1.7-fold and 1.3-fold, respectively, were observed. Exposure to 390 mosM medium for 12-48 h induced a 3-8-fold increase in cotransporter mRNA levels suggesting that the increase in myo-inositol uptake is brought about by increased cotransporter gene expression. Abrupt return of hypertonic cells to an isotonic medium induced a rapid increase in myo-inositol efflux and a return of cotransporter mRNA to control values in < 2 h. In contrast, the cotransporter remained fully activated at hypertonic levels for 16 h. Between 16-24 h after the transfer, the rate of myo-inositol uptake returned to control values. The remarkable sensitivity of the cotransporter to hypertonic stress indicates that upregulation of myo-inositol transport in glial cells is likely to occur in a variety of disease states that cause an elevation of plasma osmolality. Slow downregulation of the cotransporter may be responsible in part for the slow loss of myo-inositol and cerebral edema that occurs with too rapid correction of chronic plasma hypertonicity.
authors.affiliation: Department of Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: K
authors.initials: K
authors.lastname: Strange
authors.forename: F
authors.initials: F
authors.lastname: Emma
authors.forename: A
authors.initials: A
authors.lastname: Paredes
authors.forename: R
authors.initials: R
authors.lastname: Morrison
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001692:Biological Transport; D015152:Blotting, Northern; D001929:Brain Edema / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003470:Culture Media; D015536:Down-Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006982:Hypertonic Solutions; D007294:Inositol / Q000378:metabolism*; D008565:Membrane Proteins; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D027981:Symporters; D015854:Up-Regulation / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D003470:Culture Media; D006360:Heat-Shock Proteins; D006982:Hypertonic Solutions; D008565:Membrane Proteins; D027981:Symporters; C073884:SLC5A3 protein, human; D007294:Inositol; D012313:RNA; D012964:Sodium