Nonlinear tissue distribution of ouabain in rabbits.

Nonlinear and slow tissue distribution of ouabain was found in rabbits, and the contribution of the ouabain binding to Na+,K+-ATPase was also examined in the heart. The tissue-to-plasma concentration ratio (Kp) of ouabain in each tissue increased with time until 120 min. In addition, the Kp also depended on the plasma concentration (Cp). In the heart, Kp decreased from 12.6 +/- 1.2 to 1.9 +/- 0.2 with the increase of the Cp from 67.3 +/- 5.0 to 497 +/- d 85.2 nM. These data indicate that ouabain distributes slowly into each tissue by a saturable process. The specific binding of ouabain to cardiac Na+,K+-ATPase was measured using crude homogenates. The dissociation constant and the binding capacity were 86 nM and 2.3 nmol/ml of 0.5% homogenate, respectively. The tissue-to-plasma concentration ratio (Kp,vitro) was constructed based on these binding parameters and this explained almost 40% of the Kp obtained in vivo. These results suggest that the ouabain binding to Na+,K+-ATPase might play one of the major roles in the slow and nonlinear tissue distribution of ouabain in rabbits.