Effects of Li(+) transport and Li(+) immobilization on Li(+)/Mg(2+) competition in cells: implications for bipolar disorder.
Li(+)/Mg(2+) competition has been implicated in the therapeutic action of Li(+) treatment in bipolar illness. We hypothesized that this competition depended on cell-specific properties. To test this hypothesis, we determined the degree of Li(+) transport, immobilization, and Li(+)/Mg(2+) competition in lymphoblastomas, neuroblastomas, and erythrocytes. During a 50 mM/L Li(+)-loading incubation, Li(+) accumulation at 30 min (mmoles Li(+)/L cells) was the greatest in lymphoblastomas (11.1+/-0.3), followed by neuroblastomas (9.3+/-0.5), and then erythrocytes (4.0+/-0.5). Li(+) binding affinities to the plasma membrane in all three cell types were of the same order of magnitude; however, Li(+) immobilization in intact cells was greatest in neuroblastomas and least in erythrocytes. When cells were loaded for 30 min in a 50 mM/L Li(+)-containing medium, the percentage increase in free intracellular [Mg(2+)] in neuroblastoma and lymphoblastoma cells ( approximately 55 and approximately 52%, respectively) was similar, but erythrocytes did not exhibit any substantial increase ( approximately 6%). With the intracellular [Li(+)] at 15 mM/L, the free intracellular [Mg(2+)] increased by the greatest amount in neuroblastomas ( approximately 158%), followed by lymphoblastomas ( approximately 75%), and then erythrocytes ( approximately 50%). We conclude that Li(+) immobilization and transport are related to free intracellular [Mg(2+)] and to the extent of Li(+)/Mg(2+) competition in a cell-specific manner.
Department of Chemistry, Loyola University Chicago, 6525 N. Sheridan Rd., Chicago, IL 60626, USA.
Brian T
BT
Layden
Abde M
AM
Abukhdeir
Nicole
N
Williams
Carla P
CP
Fonseca
Laura
L
Carroll
Margarita M C A
MM
Castro
Carlos F G C
CF
Geraldes
Fred B
FB
Bryant
Duarte Mota de
DM
Freitas
D001667:Binding, Competitive; D001692:Biological Transport; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000502:physiology*; D008094:Lithium / Q000378:metabolism* / Q000627:therapeutic use; D008274:Magnesium / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology; D014407:Tumor Cells, Cultured
D008094:Lithium; D008274:Magnesium