Lithium dampens neurotransmitter response in smooth muscle: relevance to action in affective illness

Lithium, by inhibiting inositol phosphate metabolism, interferes with the phosphatidylinositol ("phosphoinositide") cycle, which is stimulated by numerous hormones and neurotransmitters. To examine the relevance of this action to neurotransmission, we evaluated effects of lithium treatment on smooth muscle responses to transmitters. In lithium-pretreated tracheal muscle, the relaxation following carbachol or histamine contractions is retarded. Lithium does not affect relaxation following contractions elicited by treatment with KCl and phorbol 12,13-diacetate in combination, which bypasses receptor stimulation of the phosphatidylinositol cycle. Half-maximal effects of lithium occur at 1 mM, corresponding to therapeutic concentrations. Dampening of neurotransmitter responses by lithium treatment may explain the unique ability of lithium to relieve and prevent both mania and depression.