The agonist-stimulated accumulation of inositol phosphates is attenuated in neutrophils from male patients under chronic lithium therapy

Abstract

Neutrophils from 22 patients (11 men, 11 women) under chronic lithium therapy and from 22 age- and sex-matched healthy controls were assessed for the activity of the agonist-stimulated inositol-phospholipid second messenger-producing system. [3H]inositol-labeled cells were stimulated with the chemotactic peptide formylmethionylleucylphenyl-alanin (fMLP). The fMLP-evoked increase in the accumulation of [3H]inositol phosphates was significantly attenuated in neutrophils from chronically lithium-treated male but not female patients. Furthermore, the fMLP-stimulated accumulation of inositol phosphates was attenuated in neutrophils from male volunteers, when the labeling of the cells with [3H]inositol was performed in the presence of 1mM Li (4 hr, 37 degrees C). However, the presence of lithium ions during the labeling did not further reduce the already diminished response of neutrophils from patients under lithium therapy. These results suggest that lithium treatment induces an inhibition of the agonist-evoked breakdown of inositol phospholipids in human cells, as already shown for rat brain slices.