Lithium transport by fibroblastic mouse cells: Characterization and stimulation by serum and growth factors in quiescent cultures

Serum enhances the rate of Li + entry and exit in quiescent cultures of mouse fibroblasts by 2‐ to 3‐fold. Tertiary cultures of whole mouse embryos as well as established fibroblast lines (3T3, 3T6) show the increase in Li + permeability when serum is added to cultures whose growth has been arrested by serum deprivation. Growing cells are only slightly more permeable to Li + in the presence of serum. Purified compounds which initiate DNA synthesis also rapidly increase Li + entry; mitogenic levels of thrombin and the combination of epidermal growth factor, insulin, and bovine serum albumin were the most effective ones tested. The effect of serum on Li + uptake occurs within a few minutes, is not affected by inhibitors of macromolecular synthesis, and appears mainly to increase the Vmax of entry. Inhibitors of energy production partially reduce Li + entry but do not block the activation by serum. One portion of Li + uptake (−40%), which is inhibited by ouabain, phloretin, or Na + deprivation, is mediated by the Na + /K + pump in the plasma membrane. A second mechanism of Li + entry which is blocked by Na + or amiloride appears to be a Na + specific “porter.” The activity of both components is stimulated by serum. The increased activity of the putative Na + porter would increase Na + availability to the Na + pump and may account for its enhancement by serum, which was also noted previously (Rozengurt and Heppel, '75).