Renal Aldosterone Receptors: Studies with [3H]Aldosterone and the Anti-Mineralocorticoid [3H]Spirolactone (SC-26304) |
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Authors: | Diana Marver John Stewart John W Funder David Feldman and Isidore S Edelman |
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Institution: | Cardiovascular Research Institute, University of California, San Francisco, Calif. 94143;Department of Medicine, University of California, San Francisco, Calif. 94143;Department of Biochemistry, University of California, San Francisco, Calif. 94143;Department of Biophysics, University of California, San Francisco, Calif. 94143 |
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Abstract: | In vivo, a spirolactone (SC-26304) inhibited the effects of aldosterone on urinary K(+):Na(+) ratios and the binding of (3)H]aldosterone to renal cytoplasmic and nuclear receptors. Cytoplasmic binding of (3)H]aldosterone and (3)H]spirolactone (SC-26304) was similar in magnitude and involved the same set of sites. Under three sets of conditions-(i) in the intact rat, (ii) in kidney slices, and (iii) in reconstitution studies (mixing prelabeled cytoplasm with either purified renal nuclei or chromatin), (3)H]spirolactone (SC-26304) did not yield specific nuclear complexes in contrast to the reproducible generation of these complexes with (3)H]aldosterone. In glycerol density gradients, cytoplasmic (3)H]aldosterone receptor complexes sedimented at 8.5 S and 4 S in low concentrations of salt and at 4.5 S in high concentrations of salt. Cytoplasmic (3)H]spirolactone (SC-26304) receptor complexes sedimented at 3 S in low concentrations of salt and 4 S in high concentrations of salt. These results are discussed in terms of an allosteric model of the receptor system. |
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