Regulation of Myo-inositol homeostasis in differentiated human NT2-N neurons.
We have investigated the possible role of second messengers on inositol homeostasis in NT2-N cells, human central nervous system neurons obtained by terminal differentiation of teratocarcinoma precursors. Uptake of inositol into NT2-N neurons was inhibited approximately 10% by protein kinase C (PKC) activation but was unaffected by either the presence of cyclic nucleotide analogs or changes in the intracellular concentration of Ca2+. Efflux of inositol from NT2-N neurons was enhanced in hypotonic buffer but virtually eliminated by inclusion of the Cl- channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, a result which indicates the involvement of a volume-sensitive organic osmolyte-anion channel. Volume-sensitive inositol efflux was stimulated approximately 30% following activation of PKC or elevation of the cytosolic Ca2+ concentration but was unaffected by protein kinase A activation. These results suggest that whereas inositol uptake into NT2-N neurons is relatively refractory to regulation, volume-sensitive inositol efflux may be significantly affected by intracellular signaling events.
Novak
J E
JE
Neuroscience Laboratory and Mental Health Research Institute, University of Michigan, Ann Arbor 48104-1687, USA.
Agranoff
B W
BW
Fisher
S K
SK
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007038:Hypotonic Solutions; D007294:Inositol / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018243:Teratocarcinoma; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured
D007038:Hypotonic Solutions; D014316:Tritium; C016276:8-bromocyclic GMP; D007294:Inositol; D015759:Ionomycin; D010095:Oxotremorine; D008094:Lithium; D011493:Protein Kinase C; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium