Increase in Na+/K+ pump numbers in vivo in healthy volunteers taking oral lithium carbonate and further upregulation in response to lithium in vitro.

1. We have measured [3H]‐ouabain binding to lymphocyte membranes in eight healthy volunteers before and after they had taken lithium carbonate for 14 days in doses which maintained the serum lithium concentration in the range 0.5‐1.0 mmol 1‐1. 2. There was a statistically significant increase in the [3H]‐ouabain binding capacity of the lymphocyte membranes (reflecting the number of Na+, K+‐ATPase molecules) after 14 days of lithium administration in vivo. This suggests that a failure to increase pump numbers after similar exposure to lithium in vivo in patients with manic‐depressive psychosis is a primary abnormality associated with the disease. 3. In vivo lithium administration did not alter the normal adaptive (upregulatory) response of lymphocyte Na+, K+‐ATPase to standard pharmacological challenges, involving in vitro incubation for 3 days with lithium chloride (8 mmol 1‐1) or sodium ethacrynate (1 mumol 1‐1). 4. We have previously found that there is an impaired response of the Na+, K+‐ ATPase to these in vitro stimuli in patients with manic‐depressive psychosis, and our present data suggest that this abnormality is attributable to the disease itself and not to in vivo lithium therapy. 5. The data also suggest that the increase in vivo Na+/K+ pump activity which we have previously described in healthy volunteers after 21 days of lithium administration is at least partly due to an increase in Na+/K+ pump numbers.