A Method for the Study of Cation Transport in vivo: Effects of Digoxin Administration and of Chronic Renal Failure on the Disposition of An Oral Load of Rubidium Chloride

Abstract

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.

In vivo cation transport during short‐term and long‐term digoxin therapy.

“…The changes in plasma rubidium concentrations reflect the overall transport of rubidium out of the plasma into the intracellular compartment, whilst the changes in intra-erythrocytic rubidium concentrations reflect transport into a single cellular compartment, which may or may not be representative of the intracellular compartment as a whole. We have previously shown that the disposition of rubidium is altered in healthy volunteers who have taken a loading dose of digoxin (Boon et al, 1984b), and in this study we have found similar changes in patients who have been taking digoxin in maintenance dosage for less than 10 days. These alterations are in a direction which is consistent with a generalized reduction in the activity of the Na+,K+-ATPase.…”

“…We have previously shown that the disposition of rubidium is altered in healthy volunteers who have taken a loading dose of digoxin (Boon et al, 1984b), and in this study we have found similar changes in patients who have been taking digoxin in maintenance dosage for less than 10 days. These alterations are in a direction which is consistent with a generalized reduction in the activity of the Na+,K+-ATPase.…”

“…The details and the rationale of this method have already been published (Boon et al, 1984b). In brief, each subject was given a total of 8 mg kg-' of rubidium chloride, divided into eight equal 28 N. A.…”

Effect of Lithium and of Other Drugs Used in the Treatment of Manic Illness on the Cation‐Transporting Properties of Na+, K+‐ATPase in Mouse Brain Synaptosomes

“…Using thlese in vitro techniques, several groups have demonstrated changes in Na+,K+-ATPase activity in both depression and mania (Naylor et al, 1973(Naylor et al, , 1976Hokin-lVeaverson et al, 1974;Hesketh et al, 1977~) and following the administration of lithium salts to both patients (Naylor et al, 1974;Hokin-Neaverson et al, 1976;Hesketh et al, 1978;Johnston et al, 1980) and healthy volunteers (Naylor et al, 1977). These studies have been extended recently in our own work, using an oral load of nonradioisotopic rubidium to assess cation transport in vivo in affective illness and following the administration of lithium (Boon et al, 1984;Wood et al, 1987aJ).…”

Changes in cation transport during affective illness: Do they have therapeutic implications?

“…Such functional changes have been demonstrated clinically during the administration of digoxin, a Na+,K+-ATPase inhibitor. Abnormalities of pump function in peripheral tissues have been reported in disease states, including hypertension (Wambach et al, 1980), and chranic renal failure (Boon et al, 1984). Others have reported abnormalities of the Na+,K+-ATPase in affective illness and in relation to treatment of patients suffering from either unipolar or bipolar affective illness.…”