Renal Aldosterone Receptors: Studies with [3H]Aldosterone and the Anti-Mineralocorticoid [3H]Spirolactone (SC-26304)

AUTOR(ES)

Marver, Diana

RESUMO

In vivo, a spirolactone (SC-26304) inhibited the effects of aldosterone on urinary K+:Na+ ratios and the binding of [3H]aldosterone to renal cytoplasmic and nuclear receptors. Cytoplasmic binding of [3H]aldosterone and [3H]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), [3H]spirolactone (SC-26304) did not yield specific nuclear complexes in contrast to the reproducible generation of these complexes with [3H]aldosterone. In glycerol density gradients, cytoplasmic [3H]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 [3H]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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