4-acetamido-4--isothiocyanatostilbene-2-2--disulfonic-acid and Bipolar-Disorder

The reproducibility of in vitro erythrocyte lithium efflux and lithium efflux in the presence of selected membrane transport inhibitors (phloretin, ouabain, 4,4'-diisothiocyano-2,2'-disulphonic acid stilbene, and p-chloromercury-benzene sulphonate) was investigated in bipolar patients and age- and sex-matched control subjects. Efflux experiments were repeated three times in each patient-control pair within a period of 14 days. No differences were detected between patients and control subjects in any of the parameters measured. All components of lithium efflux showed wide day-to-day variation in the same subject in both patients and control subjects. Intersubject variability, however, was significantly greater than intrasubject variation. Since intraindividual variation of phloretin-inhibited lithium efflux was found to be considerable, and no real patient-control differences could be detected, the significance of this in vitro parameter in bipolar affective illness seems somewhat questionable and should be carefully reconsidered. The relevance of these findings to the putative cell membrane dysfunction in this disease is discussed.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4-Chloromercuribenzenesulfonate; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Bipolar Disorder; Cell Membrane; Erythrocytes; Humans; Lithium; Ouabain; Phloretin

Erythrocyte lithium influx and efflux were investigated in vitro in patients with bipolar affective disorders and in age- and sex-matched healthy controls. To explore the components of lithium influx and efflux five selected inhibitors (ouabain, phloretin, p-chloromercury benzene sulfonate [PCMBS], 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene, and lanthanium chloride) were employed. The mean values of lithium influx were similar in both populations of erythrocytes. The addition of ouabain and phloretin reduced lithium influx, but this effect was comparable in both patients and controls. PCMBS had an accelerating effect, and this was more pronounced in patients. Total erythrocyte lithium efflux from lithium-containing erythrocytes was comparable in both patients and controls. The addition of phloretin reduced RBC lithium efflux, the magnitude of this parameter, however, was similar in patients and controls. Erythrocyte lithium efflux was accelerated in the presence of PCMBS, and this effect was greater in patients. The relevance of these findings to the postulated cell membrane defect in affective disorders is evaluated.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4-Chloromercuribenzenesulfonate; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Bipolar Disorder; Cell Membrane Permeability; Erythrocytes; Female; Humans; Lanthanum; Lithium; Male; Ouabain; Phloretin

This study examines whether variability in the efflux of lithium from erythrocytes may be a marker for manic-depressive disorder in related individuals. The subjects of the study were 73 individuals from 12 families in which there was more than one bipolar manic-depressive member. Using an in vitro procedure, we subjected erythrocytes to four conditions which are believed to inhibit lithium efflux. Only phloretin, an inhibitor of Na+-Li+ countertransport, produced significant inhibition. Variability in this inhibition was not related to the presence or absence of manic-depressive disorder, although it was related to family membership. The implications of these findings are discussed.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4-Chloromercuribenzenesulfonate; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Bipolar Disorder; Cell Membrane Permeability; Dimethyl Sulfoxide; Erythrocyte Membrane; Genetic Markers; Humans; Lithium; Ouabain; Phloretin