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 Km for I-1-P is 0.14 mM. Intriguingly, the Ki for Li+ is 0.86 mM, within the range of therapeutic concentrations in MDI patients.
Agam
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G
Ben Gurion University of the Negev, Beer Sheva, Israel.
Livne
A
A
D001714:Bipolar Disorder / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D006801:Humans; D008094:Lithium / Q000493:pharmacokinetics / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*
D008094:Lithium; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase