Lithium Reduqes the Accumulation or Inositol Polyphosphate Second Messengers Following Cholinergic Stimulation of Cerebral Cortex Slices

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Abstract
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]inpsitol monophosphate but suppressed the accumulation of the putative second messengers [3H]inositol 1,4,5‐trisphosphate ([3H]Ins(1,4,5)P3) and f3H]inositol 1,3,4,5‐tetrakisphosphate following stimulation of cerebral cortex slices with carbachol. Mass measurements of Ins(1,4,5)P3showed similar inhibitory effects, which could be prevented by preincubation with myo‐inositol. These data may reveal the mechanism by which lithium can reduce polyphosphoinositide‐midiated neurotransmission in brain.