PHYSIOLOGICAL AND PHARMACOLOGICAL PROPERTIES OF AN ENDOGENOUS SODIUM-PUMP INHIBITOR

To investigate on Na+, K+-ATPase behavior in chronic uremia, pre and p ostdialysis serum from 10 chronic dialysis patients and 10 healthy sub jects was pooled and subjected to reverse phase C-18 HPLC. Only one fr action, isolated from pre and postdialysis sera, eluting at 28 min (F- 1), was found to display significant effects on electrophysiological a nd transepithelial Na-22 flux pattern of rabbit distal colon mucosa mo unted in Ussing type chambers; indeed, serosal addition of uremic F-1 to colonic mucosa resulted in a slow, but constant, decline in short-c ircuit current (I-sc) (Delta I-sc = 1.55 +/- 0.16 mu Eq h(-1) cm(-2), mean +/- S.E.M., n = 12, p<0.01) and transepithelial conductance (G(T) ) (from 4.50 +/- 0.23 to 3.71 +/- 0.33 mS cm(-2), p<0.01, n = 12). Mea surement of transepithelial Na-22 fluces in the presence of pre or pos tdialysis sera also showed a significant Na+ absorption rate decrease (from 1.3 +/- 0.22 to 0.48 +/- 0.30 mu Eq h(-1) cm(-2), mean +/- S.E.M ., n = 4, p<0.01), mainly due to a decrease in mucosal-to-serosal Naflux. By contrast, assays of peaks isolated from healthy sera did not inhibit I-sc and transepithelial Na+ transport. The incubation of high ly purified basolateral membranes with F, for 1 min produced a similar to 26% inhibition of Na+, K+-ATPase. These findings are consistent wi th the presence of an endogenous inhibitor of sodium pump activity in uremic plasma; it is of pharmacological interest in that it may partic ipate in the development of unpredictable responsiveness to digitalis therapy in pathophysiologic states.