Inositol-1-phosphatase of human erythrocytes is inhibited by therapeutic lithium concentrations

Lithium is widely used in psychiatric chemotherapy and is especially effective in the treatment of manic-depressive illness (MDI), but the mechanism for its therapeutic properties and side effects remains to be elucidated. One of the possibilities relates to the inhibitory effect of Li⁺ on inositol-1-phosphatase (I-1-P'ase) activity. Indeed, the concentration of inositol-1-phosphate (I-1-P) after treatment with Li⁺ was shown to be increased in various mammalian cells. Yet, no direct study of I-1-P'ase activity in human cells has been reported. Erythrocytes are readily accessible for routine studies and could facilitate the investigation of I-1-P'ase as affected by Li⁺ in relation to MDI. It is now shown that I-1-P'ase can be measured in lysate of human erythrocytes, using a small blood sample. The enzymatic activity is localized in the soluble fraction. The K_m for I-1-P is 0.14 mM. Intriguingly, the K_i for Li⁺ is 0.86 mM, within the range of therapeutic concentrations in MDI patients.