Recent studies have established that urea alters the activity of sever
al volume-sensitive cation transport pathways. However, it has remaine
d unclear whether urea has any effect on transport pathways that are n
ot volume-sensitive. We examined the effect of urea on Na-K pump in th
e human erythrocytes. Ln cells from nine subjects, 500 mM urea inhibit
ed 52 +/- 10% of the pump activity measured as the ouabain-sensitive (
OS) K influx. Urea inhibited the OS K influx reversibly, in a concentr
ation-dependent manner. [H-3] oubain binding, a measure of the number
of Na-K pump sites remained unchanged with urea. Urea decreased the V-
max for ouabain-sensitive K influx, but did not alter the apparent K-m
, for external K, Furthermore, urea did not alter the apparent K-m for
intracellular Na. The ion turnover per pump site was decreased in the
presence of urea. Thus, physiologically relevant urea concentration i
nhibit the Na-K pump in human erythrocyte. The inhibition of the Na-K
pump by urea suggests that the effects of urea may not be limited to v
olume-sensitive transporters, but may be more widespread.