Chronic treatment of human astrocytoma cells with lithium, carbamazepine or valproic acid decreases inositol uptake at high inositol concentrations but increases it at low inositol concentrations.
Inositol uptake was measured at concentrations of 25, 40 and 50 microM in human astrocytoma cell cultures treated for 1-3 weeks with pharmacologically relevant concentrations of LiCl, valproic acid or carbamazepine as well as in control cultures that had not been treated with any drug. After at least 2 weeks of treatment, each of these 3 conventional anti-bipolar drugs increased the uptake significantly at 25 microM inositol, had no effect at 40 microM, and decreased it at 50 microM inositol. Reduction of the drug concentrations by 50% abolished the stimulation of uptake at 25 microM inositol by lithium and valproic acid and reduced that by carbamazepine. These findings may contribute to an understanding of the mechanisms of action for anti-bipolar medication, and explain the controversy in the literature whether or not brain inositol is reduced after chronic administration of lithium.
Wolfson
M
M
Department of Microbiology and Immunology and Stanley Center for Bipolar Disorders, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheba, Israel.
Bersudsky
Y
Y
Zinger
E
E
Simkin
M
M
Belmaker
R H
RH
Hertz
L
L
D018692:Antimanic Agents / Q000494:pharmacology*; D001254:Astrocytoma; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms; D002220:Carbamazepine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007294:Inositol / Q000493:pharmacokinetics*; D018021:Lithium Chloride / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
D018692:Antimanic Agents; D014316:Tritium; D002220:Carbamazepine; D007294:Inositol; D014635:Valproic Acid; D018021:Lithium Chloride