Influence of quinidine on the binding of [3H]-ouabain and [3H]-digoxin by human lymphocytes.

To explore the molecular basis of the glycoside-quinidine interaction, the in vitro effect of quinidine on the binding of [3H]-ouabain and [3H]-digoxin to Na + K + ATPase receptors on human mononuclear cells was investigated. The maximum [3H]-ouabain binding capacity was 45.7 +/- 9.4 X 10(3) molecules/cell in pure lymphocyte preparations (n = 8) and 75.5 +/- 7.3 X 10(3) molecules/cell in mixtures of mononuclear cells (n = 8). These parameters were not influenced by 10(-5)M quinidine. In eight equilibrium experiments with pure lymphocytes, the dissociation constant of [3H]-ouabain increased from 0.79 +/- 0.26 X 10(-8)M in the absence of 10(-5)M quinidine to 1.56 +/- 0.74 X 10(-8)M in its presence (p less than 0.01), indicating that the affinity of the drug was decreased. Similar findings were observed using mixed mononuclear cells. In five uptake and release experiments, quinidine decreased the association rate constant of [3H]-ouabain from 3.15 +/- 0.36 X 10(4)M-1 X s-1 to 2.01 +/- 0.37 X 10(4)M-1 s-1 (p less than 0.01), whereas the dissociation rate constant was not affected. A therapeutic concentration of quinidine does not affect the number of glycoside receptors on lymphocytes, but it does appear to reduce fractional receptor occupancy by both [3H]-ouabain and [3H]-digoxin at lower tracer concentrations. This finding is compatible with the clinical observation that quinidine reduces the distribution volume of digoxin.