Assessment of Neuronal Phosphoinositide Turnover and Its Disruption by Lithium

Abstract

The ability of lithium to interfere with signal transduction pathways that involve neurotransmitter receptor activation of phosphoinositide turnover has been proposed as a potential mechanistic explanation of the therapeutic actions of lithium in manic-depressive illness. Noncompetitive inhibition of inositol monophosphatase by submillimolar concentrations of lithium deprives active neurons of endogenously generated myo-inositol. If this deficit cannot be compensated for by uptake of extracellular myo-inositol, then the ability of the cell to synthesize and maintain inositol phospholipid pools will be compromised. Here we describe methods for the investigation of the phosphoinositide cycle, with particular emphasis on methods that have been used to highlight the complex actions of lithium to disrupt activation of this important signal transduction pathway by neurotransmitters.