Evidence for bicarbonate-dependent lithium reabsorption in dog kidneys

To examine whether lithium is reabsorbed along a transcellular or a paracellular route, experiments were performed in anesthetized volume-expanded dogs under conditions of constant glomerular filtration rate (GFR). Ouabain, in doses inhibiting about 80 % of Na,K-ATPase, and ethacrynic acid, another inhibitor of transcellular NaCl reabsorption, did not inhibit lithium or bicarbonate reabsorption. Lithium reabsorption increased in proportion to plasma concentration of lithium (P_Li) up to 12 mM, suggesting a passive transport of lithium. During ouabain administration acetazolamide halved bicarbonate reabsorption, the main driving force for paracellular reabsorption, and halved the reabsorption of lithium. The reabsorbate concentration of lithium, calculated from data obtained before and after acetazolamide infusion, was almost equal to P_Li. Mannitol, which reduces paracellular osmotic transport without affecting bicarbonate reabsorption, reduced lithium and chloride reabsorption in the same proportion as acetazolamide (r=0.87). Combined acetazolamide and mannitol administration reduced fractional lithium reabsorption to 0.09±0.02. These data indicate that lithium is not actively transported but reabsorbed passively along a paracellular route by osmotic forces provided by transcellular NaHCO₃ reabsorption.