Lithium amplifies inhibitions of inositol phospholipid hydrolysis in mammalian brain slices.

1. We have examined the effects of lithium chloride (LiCl) on inhibitions of inositol phospholipid hydrolysis in guinea-pig and rat brain slices by assessing the accumulation of [3H]-inositol phosphates ([3H]-InsP), in vitro. 2. In guinea-pig and rat cerebral cortex slices the accumulation of total [3H]-inositol phosphates due to the cholinoceptor agonist carbachol was inhibited by the excitatory amino acid L-glutamate, but only when LiCl was present. 3. The effects of LiCl were time and concentration-dependent. Significant inhibitions of the carbachol response by glutamate (in the presence of LiCl) being evident only after 20-30 min of stimulation at LiCl concentrations above 1.2 mM. 4. N-methyl-D-aspartate (NMDA), in the absence of LiCl, enhanced the response to carbachol at low concentrations of the amino acid and inhibited the response at higher concentrations. In the presence of 5 mM LiCl, only the inhibitory phase was observed. 5. In rat cerebral cortex slices, aluminium fluoride inhibited [3H]-InsP accumulation in the presence of carbachol, noradrenaline and a depolarising concentration of KCl and these inhibitions were more marked when LiCl was present. The response to histamine was unaffected. 6. The data presented provide evidence that LiCl amplifies inhibitions of inositol phospholipid hydrolysis due to receptor and non-receptor mediated stimuli, although the mechanism underlying the effect is, as yet, obscure.