Lithium Treatment Strongly Inhibits Choline Transport in Human Erythrocytes

Abstract

The influx of [14C] ‐choline and the efflux of 22Na in human erythrocytes were measured in vitro using blood from patients treated with lithium, patients not on lithium and healthy individuals. The administration of lithium to patients significantly reduces the transport of choline; during the first 6 weeks of treatment the influx of choline is about half the normal rate, later it falls to around 10%. This inhibition of choline transport is not dependent on the presence of lithium in the incubation medium. 4 The active and passive efflux of sodium are apparently not affected by lithium treatment.

Relation between Erythrocyte and Plasma Lithium Concentrations as an Index in Psychiatric Disease

“…their age, and if this is the case they would not reflect the conditions in other organs in the body. Within the range of our assay, there is no significant deviation from a rectilinear relationship between the erythrocyte and plasma lithium concentration as in the work of Lee et al (12), where the erythrocyte lithium was compared with plasma lithium over a wide range. In our study, it is not possible to explain the relative levels of lithium in erythrocytes as caused by differences in lithium concentration in the plasma.…”

“…Correlations with response to treatment (4, 18) and with disease have been proposed (25), but also criticized (20). Part of the disagreement may derive from the observed dependence of the erythrocytelplasma lithium ratio on the plasma lithium level (12). Fully aware of these difficulties, we further extended our previous material (14,15) to include healthy male subjects and patients from both sexes with schizophrenia, in order to investigate whether or not some disagreement in the literature could be traced to distribution variations arising from differences in sex, age and disease; especially so, since preliminary findings revealed the possibility that differences in lithium distribution between erythrocytes and plasma are not exclusive to manic-depressive disease.…”

An Irreversible Effect of Lithium Administration to Patients

“…The experiments summarized in Table 1 were designed to obtain some direct evidence concerning the relationship between intracellular lithium levels and the pronounced inhibition of choline transport that is observed after several weeks of lithium administration (Lee et al, 1974). Erythrocytes from healthy individuals were incubated for 90 min in buffers containing 4 mM or 8 mM LiCl, resulting in intracellular lithium concentrations similar to those found in patients treated with lithium.…”

“…It has recently been shown that the administration of lithium to patients reduces choline uptake into erythrocytes to around 10% of the normal value (Lee, Lingsch, Lyle & Martin, 1974). A very surprising feature of this inhibition is that it is apparently completely independent of the presence of lithium in the external medium.…”

“…The procedures for measurement of the influx of [14C]-choline and for calculation of the influx of choline into erythrocytes have been described previously (Martin, 1972;Lee et al, 1974). The rate of choline influx was determined after the cells had been incubated for 10 min at 37°C in a buffer containing 1 j.M choline.…”