Transport pathways for therapeutic concentrations of lithium in rat liver

Although both amiloride- and phloretin-sensitive Na+/Li+ exchange activitie s have been reported in mammalian red blood cells, it is still unclear whet her or not the two are mediated by the same pathway. Also, little is known about the relative contribution of these transport mechanisms to the entry of therapeutic concentrations of Li+ (0.2-2 mM) into cells other than eryth rocytes. Here, we describe characteristics of these transport systems in ra t isolated hepatocytes in suspension. Uptake of Li+ by hepatocytes, preload ed with Na+ and incubated in the presence of ouabain and bumetanide, compri sed three components. (a) An amiloride-sensitive component, with apparent K -m, 1.2 mM Li+, V-max 40 mu mol.(kg dry wt.min)(-1), showed increased activ ity at low intracellular pH. The relationship of this component to the conc entration of intracellular H+ was curvilinear suggesting a modifier role of [H+](i). This system persisted in Na+-depleted cells, although with appare nt K-m 3.8 mM. (b) A phloretin-sensitive component. with K-m 1.2 mM, V-max 21 mu mol.(kg.min)(-1), was unaffected by pH but was inactive in Na+-deplet ed cells. Phloretin inhibited Li+ uptake and Na+ efflux in parallel. (c) A residual uptake increased linearly with the external Li+ concentration and represented an increasing proportion of the total uptake. The results stron gly suggest that the amiloride-sensitive and the phloretin-sensitive Li+ up take in rat liver are mediated by two separate pathways which can be distin guished by their sensitivity to inhibitors and intracellular [H+].