Effects of Digoxin-Specific Antibodies on Accumulation and Binding of Digoxin by Human Erythrocytes

Jerry D. Gardner; Diane R. Kiino; Timothy J. Swartz; Vincent P. Butler

doi:10.1172/JCI107364

Effects of Digoxin-Specific Antibodies on Accumulation and Binding of Digoxin by Human Erythrocytes

Jerry D. Gardner, Diane R. Kiino, Timothy J. Swartz, and Vincent P. Butler Jr.

Published August 1, 1973 - More info

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Abstract

The present studies indicate that accumulation of digoxin by intact human erythrocytes is the result of two processes: binding of digoxin to the erythrocyte membrane and uptake of digoxin across the membrane into the cell. In contrast, accumulation of ouabain by human erythrocytes is entirely attributable to binding of this glycoside to the plasma membrane. Digoxin binding to the erythrocyte membrane involves a single class of binding sites, is a saturable function of the extracellular digoxin concentration, reversible, temperature-sensitive, dependent on the cation composition of the incubation medium, inhibited by other cardioactive steroids, and correlates with the inhibition of erythrocyte potassium influx. Digoxin uptake across the membrane into the cell is also temperature-sensitive and reversible but is a linear function of the extracellular digoxin concentration, not altered by changes in the cation composition of the incubation medium, not inhibited by other cardioactive steroids, and does not correlate with inhibition of erythrocyte potassium influx. Digoxinspecific antibodies can both prevent and reverse effects of digoxin on potassium influx in human erythrocytes by virtue of the capacity of the antibodies to decrease the amount of digoxin that is bound to the erythrocyte membrane. These antibodies also reduce uptake of digoxin across the plasma membrane into the erythrocyte; however, this portion of cellular digoxin is not responsible for the observed inhibition of potassium influx. In the presence of digoxin-specific antibodies, the changes in digoxin binding to the erythrocyte membrane and in digoxin uptake across the membrane into the cell reflect the ability of the antibodies to form complexes with “free” digoxin molecules in the incubation medium and thereby decrease the effective concentration of digoxin.