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Article
Mechanism and Regulation of Swelling-Activated Inositol Efflux in Brain Glial Cells
American Journal of Physiology - Cell Physiology
  • Kevin Strange
  • Rebecca Morrison
  • Lamara D. Shrode
  • Robert W. Putnam, Wright State University - Main Campus
Document Type
Article
Publication Date
7-1-1993
Catalog Record
Catalog Record
Abstract
Rat C6 glioma cells chronically acclimated to hypertonic media accumulate large quantities of inositol. When returned to isotonic conditions, the cells swell and lose inositol slowly via a four- to fivefold increase in the rate of passive inositol efflux. The inositol efflux pathway is a Na+-independent transport mechanism with low affinity for inositol and is inhibited by quinidine, quinine, various anion transport blockers, and cis-unsaturated fatty acids. Ionomycin-induced elevation of intracellular Ca2+ (Cai2+) had no effect on basal or swelling-induced inositol efflux. Inositol efflux was not inhibited by chelation of Cai2+ with 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid. In addition, Cai2+ measured with fura 2 did not change during cell swelling, indicating that increases in Cai2+ do not regulate inositol efflux. Exposure of C6 cells to 20 nM phorbol 12-myristate 13-acetate, 0.5 mM adenosine 3',5'-cyclic monophosphate (cAMP), or 50 µM forskolin had no effect on basal inositol efflux but stimulated swelling-induced inositol loss by 2.6-, 2.2-, and 3.4-fold, respectively. Exposure to the protein kinase inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine or staurosporine or downregulation of protein kinase C (PKC) activity, however, had no inhibitory effect on inositol efflux, and cellular cAMP levels were not altered by cell swelling. Taken together, these results indicate that stimulation of PKC and protein kinase A modulates the activity of the efflux pathway but is not required for swelling-induced activation. Ketoconazole, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, and gossypol, inhibitors of lipoxygenase enzymes, blocked both basal and swelling-induced inositol efflux, suggesting indirectly that lipoxygenase metabolites may be responsible for swelling-induced activation of the efflux mechanism. The characteristics of inositol efflux in C6 cells are similar to those described for volume regulatory sorbitol and taurine efflux in a number of cell types, suggesting the existence of a common transport mechanism.
Citation Information
Kevin Strange, Rebecca Morrison, Lamara D. Shrode and Robert W. Putnam. "Mechanism and Regulation of Swelling-Activated Inositol Efflux in Brain Glial Cells" American Journal of Physiology - Cell Physiology Vol. 265 Iss. 1 (1993) p. C244 - C256 ISSN: 0363-6143
Available at: http://works.bepress.com/robert_putnam/141/