Abstract
The lithium pump in human erythrocyte membranes, which is responsible for extrusion of lithium against a concentration gradient, has been found to be reversibly repressed during periods of lithium carbonate administration. The pump activity of patients prior to lithium therapy is not different from controls. The onset of repression may require several days to several weeks and occurs at specific individual threshold levels of lithium carbonate dosage. Reactivation of the lithium pump occurs sometime after the dosage is discontinued. We postulate that repression of the lithium pump results from systemically available factors which alter membrane structure, and suggest that if such changes also occur in the central nervous system, they may provide insight into one means by which lithium produces its psychotropic affects.
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References
Aronoff, M. S., Evens, R. G., Durell, J.: Effect of lithium salts on electrolyte metabolism. J. Psychiatr. Res. 8, 139–159 (1971)
Baer, L., Platman, S. R., Fieve, R. R.: The role of electrolytes in affective disorders: sodium, potassium and lithium ions. Arch. Gen. Psychiatry 22, 108–113 (1970)
Baldessarini, R. J., Yorke, C.: Effects of lithium and of pH on synaptosomal metabolism of noradrenaline. Nature 228, 1301–1303 (1970)
Bunney, W. E., Jr., Murphy, D. L.: Neurobiological considerations on the mode of action of lithium carbonate in the treatment of affective disorders. Pharmakopsychiatr.-Neuropsychopharmakol. 9, 142–147 (1976)
Cazzullo, C. L., Smeraldi, E., Sacchetti, E. S., Botinelli, S.: Intracellular lithium concentration and clinical response. Br. J. Psychiatry 126, 298–300 (1975)
Colburn, R. W., Goodwin, F. K., Bunney, W. E., Jr., Davis, J. M.: Effect of lithium on the uptake of noradrenaline by synaptosomes. Nature 215, 1395–1397 (1967)
Coppen, A., Shaw, D. M., Melleson, A., Costain, R.: Mineral metabolism in mania. Br. Med. J. 1, 71–75 (1966)
Dousa, T., Hechter, O.: The effect of NaCl and LiCl on vasopressin sensitive adenyl cyclase. Life Sci. 9, 765–770 (1970)
Duhm, J., Eisenried, F., Becker, B. F., Greil, W.: Studies on the lithium transport across the red cell membrane. I. Li+ uphill transport by the Na+-dependent Li+ counter-transport system of human erythrocytes. Pflügers Arch. 364, 147–155 (1976)
Elizur, A., Shopsin, B., Gershon, S., Ehlenberger, A.: Intra: extracellular lithium ratios and clinical course in affective states. Clin. Pharmacol. Ther. 13, 947–952 (1972)
Forn, J., Valdecasas, F. G.: Effect of lithium on brain adenyl cyclase activity. Biochem. Pharmacol. 20, 2773–2779 (1971)
Glen, A. I. M., Bradbury, M. W. b., Wilson, J.: Stimulation of the sodium pump in the red blood cell by lithium and potassium. Nature 239, 399–401 (1972)
Goodwin, F. R., Sack, R. L., Post, R. M.: Clinical evidence for neurotransmitter adaptation in response to antidepressant therapy. In: Neurobiological mechanisms of adaptation and behavior, A. J. Mandel, ed. New York: Raven Press 1975
Haas, M., Schooler, J., Tosteson, J. C.: Coupling of lithium to sodium transport in human red cells. Nature 258, 425–429 (1975)
Katz, R. I., Kopin, I. J.: Release of norepinephrine-3H and serotonin-3H evoked from brain slices by electrical stimulation—calcium dependency and the effects of lithium, ouabain and tetrodotoxin. Biochem. Pharmacol. 18, 1935–1939 (1969)
Knorring, L., Oreland, L., Perris, S., Wiberg, A.: Evaluation of the lithium RBC/plasma ratio as a predictor of the prophylactic effect of lithium treatment in affective disorders. Pharmakopsychiatr. Neuropsychopharmakol. 9, 81–84 (1976)
Kuriyama, K., Speken, R. S.: Effect of lithium on content and uptake of norepinephrine and 5-hydroxytryptamine in mouse brain synpatosomes and mitochondria. Life Sci. 9, 1213–1220 (1970)
Maizels, M.: Effect of sodium content on sodium efflux from human red cells suspended in sodium-free media containing potassium, rubidium, caesium or lithium chloride. J. Physiol. (Lond.) 195, 657–679 (1968)
Mandell, A. J., Knapp, S.: A neurobiological model for the symmetrical prophylactic action of lithium in bipolar affective disorder. Pharmakopsychiatr. Neuropsychopharmakol. 9, 116–126 (1976)
Marini, J. L.: On the significance of the erythrocyte lithium to plasma lithium ratio. Br. J. Psychiatry 130, 139–143 (1977)
Meltzer, H. L., Rosoff, C., Kassir, S., Fieve, R. R.: Active efflux of lithium from erythrocytes of manic-depressive subjects. Life Sci. 9, 371–380 (1976)
Mendels, J., Frazer, A.: Intracellular lithium concentration and clinical response. Towards a membrane theory of depression. J. Psychiatr. Res. 10, 9–18 (1973)
Mendels, J., Frazer, A.: Alterations in cell membrane activity in depression. Am. J. Psychiatry 131, 1240–1246 (1974)
Murphy, D. L., Donnelly, C., Moskowitz, J.: Inhibition by lithium of prostaglandin E1 and norepinephrine effects on cyclic adenosine monophosphate production in human platelets. Clin. Pharmacol. Ther. 14, 810–814 (1973)
Naylor, G. N., Dick, D. A. T., Dick, E. G.: Erythrocyte membrane cation carrier relapse rate of manic-depressive illness and response to lithium. Psychol. Med. 6, 257–263 (1976)
Ploeger, E. J., Den Hertog, A.: The effects of lithium on excitable cell membranes. II. The effect on the electrogenic sodium pump of non-myelinated nerve fibres of the rat. Eur. J. Pharmacol. 21, 24–29 (1973)
Rafaelson, O. J., Mellerup, E. T., Schapiro, R. W.: Lithium in the living organism. Is an integrated hypothesis feasible? Pharmakopyychiatr. Neuropsychopharmakol. 9, 108–115 (1976)
Thomas, R. C., Simon, W., Oehme, M.: Lithium accumulation by snail neurons measured by a new Li+-sensitive microelectrole. Nature 258, 754–757 (1975)
Vendsborg, P. B., Mellerup, E. T., Rafaelson, O. J.: Lithium in man. Serum electrolytes and glucose after a single lithium load. Acta Psychiatr. Scand. 49, 97–103 (1973)
Vendsborg, P. B., Rafaelson, O. J.: Lithium in man. Effects on glucose tolerance and serum electrolytes. Acta Psychiatr. Scand. 49, 601–610 (1973)
Walker, J. B.: The effect of lithium on hormone-sensitive adenylate cyclase from various regions of the rat brain. Biol. Psychiatry 8, 245–251 (1974)
Wang, Y. C., Pandy, G. N., Mendels, J., Frazer, A.: Effect of lithium on prostaglandin E1-stimulated adenylate cyclase activity of human platelets. Biochem. Pharmacol. 23, 845–855 (1974)
Zerbi, F., Fenoglio, L., Tosca, P.: Plasma and erythrocyte concentrations of lithium. Psychiatr. Clin. 8, 236–242 (1975)
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Meltzer, H.L., Kassir, S., Dunner, D.L. et al. Repression of a lithium pump as a consequence of lithium ingestion by manic-depressive subjects. Psychopharmacology 54, 113–118 (1977). https://doi.org/10.1007/BF00426765
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DOI: https://doi.org/10.1007/BF00426765