1. Reduced Na+, K+ pump activity has been reported in uraemic erythrocytes, and this has been attributed to the presence of a circulating ouabain-like inhibitor. Since we have previously reported marked suppression of Na+, K+ co-transport activity in erythrocytes from dialysis patients, we have now examined the effect of incubation with uraemic plasma on Na+ efflux through the Na+, K+ pump and the co-transport pathway in normal erythrocytes from both men and women.

2. The results show that Na+ efflux via the Na+, K+ pump is not different between men and women (3.14 ± 0.14 vs 3.68 ± 0.18 mmol h−1 litre−1 of cells) and is not inhibited by incubation with uraemic plasma.

3. In contrast, co-transport-mediated Na+ efflux is lower in erythrocytes from normal women when compared with normal men (0.17 ± 0.02 vs 0.25 ± 0.05 mmol h−1 litre−1 of cells, P < 0.001).

4. Moreover, incubation with uraemic plasma causes stimulation of Na+ efflux through the co-transport pathway in erythrocytes of healthy women (0.17 ± 0.02 vs 0.27 ± 0.03 mmol h−1 litre−1 of cells, P < 0.005), but not in erythrocytes of healthy men (0.27 ± 0.03 vs 0.25 ± 0.05 mmol h−1 litre−1 of cells).

5. Our data do not support the presence of either a Na+, K+ pump or a co-transport inhibitor in plasma from dialysed uraemic patients. Thus, the suppressed co-transport activity demonstrated in uraemic erythrocytes cannot be attributed to a circulating inhibitor, and may reflect an acquired membrane or transport defect.

6. The stimulation of co-transport by uraemic plasma from women provides a further example of sex-determined characteristics in human erythrocytes, the mechanism of which remains to be elucidated.

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