Brief chronic effects of lithium administration on rat brain phosphoinositides and phospholipids.

Lithium is known to exert its biochemical action on cells and tissues by inhibiting the enzymic conversion of inositol monophosphates to inositol. However, it is not clear whether this inhibitory action may lead to changes in the de novo biosynthesis of phosphatidylinositol and its phosphorylated derivatives. This biosynthetic scheme may have an important bearing with regard to the receptor-mediated signal transduction mechanism involving hydrolysis of polyphosphoinositides and release of inositol trisphosphate as second messenger for mobilization of intracellular calcium. In this study, the effects of brief chronic lithium administration on metabolism of brain phosphoinositides and other phospholipids were examined using the radiotracer technique with 32Pi as precursor. Sprague Dawley rats that were treated with lithium (3-4 meq/kg body wt) twice daily for 2-6 days consistently indicated an increase in the labeling of phosphatidylinositol 4,5-bisphosphates and a decrease in labeling of phosphatidylinositols and phosphatidylethanolamines. These phospholipid changes were found in both cortex and hippocampus and appeared to occur primarily in the synaptosomal fraction. Although the extent of the phospholipid changes could vary depending on both duration and dose levels of the lithium administered, these results demonstrated subtle effects of lithium on depressing the biosynthesis of phosphatidylinositol as well as phosphatidylethanolamine but perhaps a compensative increase in the synthesis of the phosphatidylinositol 4,5-bisphosphates.