Physiological and Pharmacological Properties of an Endogenous Sodium Pump Inhibitor

To investigate on Na+, K+ - ATPase behavior in chronic uremia, pre and postdialysis serum from 10 chronic dialysis patients and 10 healthy subjects was pooled and subjected to reverse phase C-18 HPLC. Only one fraction, isolated from pre and postdialysis sera, eluting at 28 min (F1), was found to display significant effects on electrophysiological and transepithelial 22Na flux pattern of rabbit distal colon mucosa mounted in Ussing type chambers; indeed, serosal addition of uremic F1 to colonic mucosa resulted in a slow, but constant, decline in short-circuit current (Isc) (ΔIsc=1.55±0.16 μEq h−1 cm−2, mean ± S.E.M., n=12, p<0.01) and transepithelial conductance (GT) (from 4.50±0.23 to 3.71±0.33 mS cm−2, p<0.01, n=12). Measurement of transepithelial 22Na fluxes in the presence of pre or postdialysis sera also showed a significant Na+ absorption rate decrease (from 1.3±0.22 to 0.48±0.30 μEq h−1 cm−2, mean ± S.E.M., n=4, p < 0.01), mainly due to a decrease in mucosal-to-serosal Na+ flux. By contrast, assays of peaks isolated from healthy sera did not inhibit Isc and transepithelial Na+ transport. The incubation of highly purified basolateral membranes with F1 for 1 min produced a ∼26% inhibition of Na+, K+-ATPase. These findings are consistent with the presence of an endogenous inhibitor of sodium pump activity in uremic plasma; it is of pharmacological interest in that it may participate in the development of unpredictable responsiveness to digitalis therapy in pathophysiologic states.