Lithium reduces the accumulation of inositol polyphosphate second messengers following cholinergic stimulation of...

The ability of lithium to interfere with the metabolism of inositol phosphates in brain may underlie its therapeutic action in manic-depressive illness. In these experiments, lithium, at therapeutic concentrations, enhanced the accumulation of [3H]inositol monophosphate but suppressed the accumulation of the putative second messengers [3H]inositol 1,4,5-trisphosphate [( 3H]Ins(1,4,5)P3) and [3H]inositol 1,3,4,5-tetrakisphosphate following stimulation of cerebral cortex slices with carbachol. Mass measurements of Ins(1,4,5)P3 showed similar inhibitory effects, which could be prevented by preincubation with myo-inositol. These data may reveal the mechanism by which lithium can reduce polyphosphoinositide-mediated neurotransmission in brain.