Molecular Pharmacology, Vol 2, 10-21, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Association of Alkali Metal and Alkaline Earth Cations with Subcellular Particles Prepared from Renal Cortex

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

A differential centrifugation procedure was used to separate homogenized renal cortex of normal dogs into four sediments and four supernatants, each of which was analyzed for alkali and alkaline earth cations and for dry weight. The amount of each of the cations associated with, or "bound" by, the particles sedimenting in each step was computed by a method which takes into account trapped supernatant. Trace cations were determined radiometrically, except for lithium, which was administered by priming injection and constant infusion for 2 hr prior to nephrectomy. The extent of association of each cation with each of the four types of particles was expressed as the percentage of total tissue cation sedimenting with those particles. For the largest ("nuclear") particles, the extent of association of five alkali cations averaged 5.6%, and of four alkaline earths (Mg, Ca, Sr, and Ba) averaged 24%; no selectivity was seen in either group. The second largest ("mitochondrial") particles showed pronounced selectivity, the extent of association increasing from 2% to 15% with increasing atomic weight in the first group, and from 19% to 70% in the second. The third ("heavy microsomal") fraction showed no selectivity; an average of 1.4% of the alkaline cations and 6.7% of the alkaline earths was associated with these particles. The fourth ("light microsomal") fraction showed the following selectivity in order of increasing atomic weight: Li = Na > K < Rb = Cs; Mg> Ca> Sr « Ba.

Thus the "mitochondrial" particles preferentially adsorb (or take up during homogenization) larger cations in both groups, while the "light microsomal" particles show least binding of cations of intermediate size. The sequence of tissue-to-plasma ratios of alkaline earths was similar to the sequence of their association with the "light microsomal" particles. For alkali cations, tissue-to-plasma ratios paralleled the extent of their association with the "mitochondrial" particles.

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ACKNOWLEDGMENTS This work was supported by a U. S. Public Health Service Research Grant (AM02306). M. Walser was supported by the U. S. Public Health Service Research Career Award Program (GM-K3-2583). V. E. Nahmod was supported by a Lederle International Fellowship.