Lithium does not directly alter agonist-stimulated phosphoinositide-specific phospholipase C activation in rat brain...

The effects of Li(+) on phosphoinositide-specific phospholipase C activation in rat cerebral cortical slices and membranes were examined. In rat brain cortical slices labeled with [(3)H]inositol, the accumulation of labeled inositol phosphates due to carbachol was enhanced in the presence of Li(+). There was no greater effect of Li(+) in the presence of agonists if slices were exposed to 20 mM Li(+) for 6 h and then tested in the presence of Li(+) or if slices were prepared from rats injected twice daily with 10 meq/kg of LiCl or NaCl for 3 days. In membranes prepared from cortical slices, Li(+) had no effect on basal or on guanosine 5-O-(3-thio)triphosphate (GTPgammaS) or GTPgammaS plus carbachol stimulation of phospholipase C activity. The activation of phospholipase C in brain membranes by 1 mM carbachol or 100 muM norepinephrine in the presence of GTPgammaS was not affected if membranes were prepared from rats injected for 3 days with LiCl. In conclusion, Li(+)in vitro does not alter phospholipase C activation by carbachol or norepinephrine in brain cortical membranes.