Lithium inhibits the cytolytic glucocorticoid effect on S49 mouse lymphoma cells.
Cytolysis is the end point of receptor-mediated effects of glucocorticoids on S49 mouse lymphoma cells of wild-type. In the presence of 5 mM LiCl this effect of triamcinolone or dexamethasone was markedly delayed. The cytoprotective effect of Li+ against 10(-7) M triamcinolone acetonide was already manifest after 24 h of steroid incubation, and on the fifth day 50-fold more Li+-treated than control cells were viable. This effect of Li+ was not exerted through changes of the doubling time of the cells, and thus could not be ascribed to an overall reduction of protein- or RNA synthesis. Data on accumulation and effect of cyclic AMP indicated that the cytoprotective effect was independent on cyclic AMP. Furthermore Li+ did not affect the amount or affinity of glucocorticoid receptors in intact cells. By use of aqueous 2-phase partitioning and DNA-Sepharose binding of [3H]triamcinolone acetonide labelled cytosols we demonstrate that Li+ inhibits the in vitro salt-activation of the glucocorticoid-receptor complexes by 60-100%. The nuclear bound fraction of hormone-receptor complexes in intact cells at 37 degrees C was not affected by Li+. The data suggest that Li+ inhibits the cytolytic glucocorticoid effect by interacting with the hormone-receptor complexes.
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism / Q000633:toxicity*; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008223:Lymphoma / Q000503:physiopathology*; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000378:metabolism / Q000633:toxicity*
D002712:Chlorides; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone; D008094:Lithium; D000242:Cyclic AMP; D014222:Triamcinolone Acetonide; D018021:Lithium Chloride