Kinetics of ouabain outflow from isolated frog heart evaluated by the dose-effect relationship and compared to the outflow kinetics of the tritiated drug.

In isolated frog hearts the kinetics of ouabain disappearance from the receptor biophase(s) related to the effect has been calculated from the relationship between ouabain concentration and its inotropic effect. When 10(-4) - 10(-5) M ouabain is added to the heart, the kinetics is biexponential with a fast component with a time constant of 1.7 min-1 and a slower component with a time constant of 0.28 min-1. The kinetics of the washout curve of 3H ouabain (added together with unlabelled drug, shows, in addition to the slow exponential component of about the same time constant (0.2 min-1) previously seen, another component with a 10 times longer time constant, related to ineffective drug concentrations and corresponding to a washout from aspecific sites. The kinetics of ouabain outflow from compartments which are related to the effect elicited by 10(-4) - 10(-5) M concentrations is formed mainly by two steps with time constants of 1.7 min-1 and 0.28 min-1.