Molecular Pharmacology, Vol 2, 22-36, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of Ouabain on Renal Tubular Reabsorption and Cortical Concentrations of Several Cations and on Their Association with Subcellular Particles

¹ Department of Pharmacology and Experimental Therapeutics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

Ouabain was infused into one renal artery at 5 or 10 µg/kg/min for 5 or 20 min, in dogs receiving a constant infusion of ¹³⁷Cs and ⁸⁵Sr. Plasma K and Cs rose at 20 min, but plasma Na, Mg, Ca, and Sr were unaffected. Renal cortical K became partially replaced with Na and Mg with Ca, even in the uninfused kidneys. Cortical Cs, however, rose at first and later fell. At the smaller dose, tubular reabsorption of all six cations was simultaneously inhibited in the infused kidney and stimulated in the uninfused kidney. At the larger dose, a disproportionate inhibition of Cs reabsorption occurred, while alkaline earth reabsorption was inhibited relatively little, when compared with Na and K. The extent of association of these cations with four particulate fractions obtained by differential centrifugation of homogenized cortex was measured in the same animals. Changes were seen which could be tentatively correlated with the changes in transport. Addition of comparable amounts of ouabain to normal kidneys during homogenization in the cold had no such effects on subcellular binding.

The results suggest that ouabain in small doses may stimulate tubular transport by increasing cation binding by particles found in the fourth ("light microsomal") sediment; inhibition of cellular accumulation of cations and later of transport may be a result of altered selectivity of particles found in the third ("heavy microsomal") sediment for ions in relation to their size.

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ACKNOWLEDGMENTS This work was supported by a U. S. Public Health Service Research Grant (AM-2306). V. E. Nahmod was supported by Lederle International Fellowship. M. Walser was supported by the U. S. Public Health Service Research Career Award Program (GM-K3-2583).