myo-Inositol reverses Li+-induced inhibition of phosphoinositide turnover and ornithine decarboxylase induction during early lymphocyte activation.
One of the earliest detectable responses by T lymphocytes in vitro to various mitogenic ligands is the rapid induction of ornithine decarboxylase (ODC) activity (Scott et al., Eur. J. Immunol. 1985. 15: 783). This early activation is measurable within minutes after the addition of the mitogen. The T cell mitogen concanavalin A also induces rapid breakdown of phosphoinositides in T lymphocytes. The inositol phosphates formed are recycled and used in synthesis of new phosphoinositides. Li+ interrupts this cycle by inhibiting the enzyme inositol-1-phosphatase, which produces the inositol needed for phosphoinositide synthesis. Here we report that when human blood lymphocytes are kept in an inositol-deficient medium for 30 min in the presence of 1 mM Li+, the cells become unable to respond to mitogens by inositide breakdown and rapid induction of ODC activity. Addition of 1 mM myo-inositol restores the inducibility of these responses within a few minutes. These findings represent a novel aspect of the activation of resting lymphocytes and implies a new role for the inositol turnover during signal transduction.
D002712:Chlorides / Q000037:antagonists & inhibitors*; D003864:Depression, Chemical; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007294:Inositol / Q000494:pharmacology*; D008094:Lithium / Q000037:antagonists & inhibitors*; D018021:Lithium Chloride; D008213:Lymphocyte Activation / Q000187:drug effects*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D002712:Chlorides; D010716:Phosphatidylinositols; D007294:Inositol; D008094:Lithium; D009955:Ornithine Decarboxylase; D018021:Lithium Chloride