title: Upregulation of inositol transport mediates inositol accumulation in hyperosmolar brain cells.
abstract: Attempts to understand brain volume regulation have been greatly hampered by the structural complexity of the mammalian central nervous system, indicating a need for the investigation of cultured brain cell lines whose behavior reflects that observed in situ. We demonstrate here that rat C6 glioma cells exhibit a pattern of hyperosmolar volume regulation qualitatively similar to that of the intact brain. Chronic (2-6 days) acclimation of C6 cells to high NaCl media (440 or 590 mosM) resulted in a 46-133 mM increase in cellular inositol, a known major brain osmolyte. C6 cells exposed acutely to 440 mosM medium shrank abruptly and then underwent a complete regulatory volume increase (RVI) within 4 h. Inositol levels began to increase after 10 h of hyperosmolar stress and reached maximal values by 24 h, suggesting that RVI is initially mediated by inorganic ion uptake. [3H]inositol uptake measurements revealed a sevenfold stimulation of phlorizin-inhibitable inositol transport in hyperosmotic cells. The enhancement of inositol transport paralleled the rise in cellular inositol content. Phlorizin reduced inositol accumulation in hyperosmolar cells by 44%. Our studies provide the first demonstration of RVI and organic osmolyte accumulation in a cultured brain cell line.
authors.affiliation: Department of Medicine, Children's Hospital, Boston, Massachusetts.
authors.forename: K
authors.initials: K
authors.lastname: Strange
authors.forename: R
authors.initials: R
authors.lastname: Morrison
authors.forename: C W
authors.initials: CW
authors.lastname: Heilig
authors.forename: S
authors.initials: S
authors.lastname: DiPietro
authors.forename: S R
authors.initials: SR
authors.lastname: Gullans
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005910:Glioma; D007294:Inositol / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009994:Osmolar Concentration; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats
chemical_list: D007294:Inositol; D010695:Phlorhizin