Kennedy_1989_J.Neurochem_53_1652

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.