Molecular Pharmacology, Vol 6, 54-60, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Study of the Mechanism of Renal Vacuologenesis Induced in the Rat by Ethylenediaminetetraacetate

Comparison of the Cellular Activities of Calcium and Chromium Chelates

¹ United States Naval Medical Research Institute, National Naval Medical Center, Bethesda, Maryland 20014

Ca-EDTA-¹⁴C, ⁴⁵Ca-EDTA, Cr-EDTA-¹⁴C, and ⁵¹Cr-EDTA were administered individually to rats. Radioactivity was found in the renal cortical cells in all cases, and was partly sedimentable. The activities derived from the two chromium forms were equal in the compartments studied, whereas radioactivity from the two calcium forms followed separate courses. The chromium remained attached to the EDTA, whereas the calcium probably was removed or exchanged for endogenous metal ions. Both chromium chelates were distributed in the same manner as the radioactivity from Ca-EDTA-¹⁴C in renal cortical cells, 1 and 24 hr after administration, except for the supernatant fraction at 24 hr, which contained higher levels derived from Ca-EDTA-¹⁴C. On sucrose-water density gradients, radioactivity from administered Ca-EDTA-¹⁴C and the two chromium forms formed peaks in the same density zone as lysosomal acid phosphatase, while the peak for radioactivity from administered ⁴⁵Ca-EDTA coincided with that for mitochondrial cytochrome oxidase. These findings, in conjunction with histological observations, suggest that EDTA-induced vacuologenesis is a reflection of the induction of pinocytosis by the chelate.

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ACKNOWLEDGMENTS The authors are grateful to Dr. Martin Rubin, Department of Biochemistry, Georgetown University, Washington, D. C., for his advice and suggestions during the preparation of this manuscript.