One hypothesis of the anti-mania reaction mechanism of lithium salts is that they act on Na, K-ATPase, but the datails are not yet clear. We studied the effects of lithium salts on Na, K-ATPase in rat brain. The ATP hydrolysis activity of Na, K-ATPase is accelerated to its maximum in the presence of both Na and K (Na, K-ATPase activity), but only about one-tenth of the activity is observed in the presence of Na alone (Na-ATPase activity) . Addition of K to the Na-ATPase condition increased the ATPase activity, depending on its concentration, and the activity reached the maximum level. Additions of Li-acetate, Li-chloride, and Li-carbonate also increased the activity, to 75%, 57%, and 24%, respectively, of the level obtained with K. However, Li salts failed to increase the ATP hydrolysis activity in the presence of both Na and K. Ten mM K and Li reduced the amount of phosphorylated intermediate (EP) of Na, K-ATPase, to 9 % and 72%, respectively, of the maximum level observed in the presence of 40 mM Na. These findings indicate that the two ions accelerate dephosphorylation of EP, but to different degrees. The results suggest that Li has weak K-like effects and promotes Na-ATPase activity by accelerating dephosphorylation of EP.
