Elevated phosphatidyl-CMP is not the source of diacylglycerol accumulation induced by lithium in NG108-15 cells.
Previous studies have shown that in the neuroblastoma x glioma hybrid cell line NG108-15 lithium is able to induce an increase in diacylglycerol levels. This effect was shown to be enhanced by the presence of bradykinin. Another striking effect of lithium was a marked gain in the level of the liponucleotide phosphatidyl-CMP. Increased phosphatidyl-CMP levels were detected in the presence of lithium alone but were considerably more pronounced in the presence of both lithium and bradykinin. These results are consistent with the inhibitory action of lithium on key enzymes of the degradation pathway of inositol phosphates, resulting in a decrease in cellular inositol content and in an elevation in levels of phosphorylated inositols. Comparison of the mass of the inositol phosphates and diacylglycerol showed that the lithium-induced diacylglycerol levels were substantially greater than would be expected from phosphoinositide hydrolysis alone. One possible reason for the increase in the level of diacylglycerol through the action of lithium is the reversal of the reaction for the formation of phosphatidyl-CMP. The resulting phosphatidic acid would then need to be further dephosphorylated to diacylglycerol. The lithium-induced elevation of phosphatidyl-CMP was prevented by addition of myo-inositol (10-30 mM), suggesting that the increase in liponucleotide level was due to depletion of cellular inositol. Under the same conditions the elevated diacylglycerol concentration remained unchanged. Consequently, phosphatidyl-CMP is not its source, and diacylglycerol may arise through an effect of lithium on the degradation of phospholipids other than phosphoinositides. The action of phospholipase C or D on phosphatidylcholine is the most likely mechanism.
Brami
B A
BA
Ralph Lowell Laboratories, McLean Hospital, Belmont, MA 02178.
Leli
U
U
Hauser
G
G
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003568:Cytidine Monophosphate / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006822:Hybrid Cells / Q000378:metabolism*; D007294:Inositol / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010712:Phosphatidic Acids / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D010712:Phosphatidic Acids; D007294:Inositol; D008094:Lithium; D003568:Cytidine Monophosphate; D001920:Bradykinin