digoxin and rubidium-chloride

Inside-out as well as right-side-out oriented (Na+ + K+)-ATPase molecules reconstituted in liposomes are activated successively by timed asymmetric addition of ATP to the internal and external liposome compartment; this presents the first functional confirmation of the symmetric pump-orientation in cholate-dialysed preparations revealed previously by the equal distribution of intramembrane particles on the concave and convex surface of freeze-fractured (Na+ + K+)-ATPase-liposomes. The initial transport rates of the symmetrically oriented pump populations are regulated by varying the bilateral K or Rb ion concentrations; ATP, ouabain, digoxin or vanadate are used to activate or block selectively the right-side-out, inside-out or both (Na+ + K+)-ATPase populations. Finally, these liposomes of the second generation present a new tool to evaluate the membrane-permeability as well as the effects of receptor-ligands or other probes in a single preparation.

Topics: Adenosine Triphosphate; Biological Transport; Cardiac Glycosides; Cations, Monovalent; Chlorides; Digoxin; Ion Channels; Liposomes; Ouabain; Potassium; Rubidium; Sodium-Potassium-Exchanging ATPase; Vanadates; Vanadium

We have studied the effects of digoxin on cation transport in vivo by measuring the changes in plasma and red cell rubidium concentrations following an oral load of rubidium chloride. In eight patients who had been taking digoxin for 7 to 10 days (mean plasma digoxin concentration 1.3 ng ml-1) the rise in plasma rubidium concentrations was enhanced and the rise in red cell rubidium concentrations was attenuated following the oral load of rubidium chloride, by comparison with the changes in well-matched controls. In contrast, the disposition of rubidium was not altered in 12 patients who had been taking digoxin for more than 3 months (mean plasma digoxin concentration 1.1 ng ml-1). These results suggest that the inhibitory effects of digoxin on cation transport are detectable in vivo during short-term therapy, but not during long-term therapy, and confirm our previous in vitro findings.

Topics: Adult; Aged; Biological Transport; Cations; Chlorides; Digoxin; Drug Administration Schedule; Erythrocytes; Humans; Male; Middle Aged; Rubidium

In order to study cation transport in vivo the changes in plasma and red cell rubidium concentrations were measured following an oral load of rubidium chloride. Eight patients receiving short-term digoxin therapy, 10 patients with chronic renal failure and 22 patients with untreated essential hypertension were studied, and the findings were compared with those in healthy control subjects matched for age, sex, race, obesity index, and plasma and red cell potassium concentrations. In patients receiving short-term digoxin therapy, and in patients with chronic renal failure, the increases in plasma rubidium concentrations after the oral load of rubidium chloride were significantly enhanced and the increases in red cell rubidium concentrations were significantly attenuated. These findings are consistent with a generalized reduction in Na+, K+-ATPase activity in vivo. In contrast, in patients with untreated essential hypertension the increases in both plasma and red cell rubidium concentrations following the oral load were significantly enhanced. These data do not support the hypothesis that essential hypertension is associated with reduced Na+, K+-ATPase activity in vivo, at least in the red cell.

Topics: Adult; Aged; Biological Transport; Cations; Chlorides; Digoxin; Erythrocytes; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Rubidium; Sodium-Potassium-Exchanging ATPase; Time Factors

In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations following an oral load of rubidium chloride. The changes in plasma rubidium concentration are related to the distribution of rubidium to all the body tissues and the changes in intra-erythrocytic rubidium concentrations provide an example of rubidium uptake by one particular tissue. In eight healthy volunteers pretreatment with a loading dose of digoxin (20 micrograms/kg) enhanced the rise in plasma rubidium concentrations and attenuated the rise in intra-erythrocytic rubidium concentrations after the oral load of rubidium chloride. Ten patients with chronic renal failure, compared with a well-matched control group, were found to have changes similar to, but more marked than, those caused by digoxin, i.e. a much greater rise in plasma rubidium concentrations and a much smaller rise in intra-erythrocytic rubidium concentrations, after the oral load of rubidium chloride. These findings are consistent with wide-spread reduction in Na+, K+-ATPase activity in subjects who have taken a loading dose of digoxin and patients with chronic renal failure. They are, therefore, consistent with the findings of previous studies in vitro and show that it is possible to demonstrate changes in cation transport in vivo.

Topics: Adult; Biological Transport, Active; Chlorides; Digoxin; Erythrocytes; Female; Humans; Kidney Failure, Chronic; Male; Methods; Middle Aged; Rubidium; Time Factors