Effects of ouabain on monovalent cation transport in mammalian tissue.
We measured the effects of ouabain on sodium-potassium ATPase (Na-K ATPase) specific activity (SA) and rubidium (Rb) transport in newborn (NB) and adult (Ad) sheep myocardium (myo), guinea pig myo and red blood cells (RBC), and human RBC. 50% inhibition of Na-K ATPase SA and Rb transport occurred at ouabain concentrations between 10(-4.8) and 10(-7.6) M in different species; within a species, 50% inhibition of Rb transport occurred at lower ouabain concentrations than 50% inhibition of Na-K ATPase SA. No differences between mature and immature tissues were found. Ouabain binding stability to Na-K ATPase extracted from myo and RBC did not vary with age. Binding studies revealed a KD X 10(-8) M of 0.87 +/- 0.09 for NB human RBC and 0.88 +/- 0.14 for Ad human RBC. Calculated RBC receptor density however, was higher in the Ad (1.25 +/- 0.08 sites/micron2) than in the NB (1.03 +/- 0.04 sites/micron2, p less than 0.01). Binding studies in extracted myocardial specimens showed a KD X 10(-8) M of 1.23 +/- 0.27 for NB and 1.09 +/- 0.46 for Ad; mM ouabain bound X 10(-12)/Na-K ATPase unit were 355 +/- 120 (SEM) for NB and 316 +/- 51 for Ad. These studies of cardiac glycosides reveal few age-related differences in drug binding or inhibition of monovalent cation transport.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002414:Cations, Monovalent / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010042:Ouabain / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D012413:Rubidium / Q000378:metabolism; D012756:Sheep; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013045:Species Specificity
D002414:Cations, Monovalent; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium