What question did this study set out to answer?

This research investigates how spirolactone interacts with aldosterone receptors in renal tissues.

April 1, 1974Proceedings of the National Academy of Sciences132 citationsOpen Access

Renal Aldosterone Receptors: Studies with 3 HAldosterone and the Anti-Mineralocorticoid 3 HSpirolactone (SC-26304)

DMDiana MarverNational Institutes of Health JSJohn P StewartUniversity of California, San Francisco JFJohn W. FunderHudson Institute

Key Points

This research investigates how spirolactone interacts with aldosterone receptors in renal tissues.
In vivo assessment of spirolactone effects on urinary K(+):Na(+) ratios and receptor binding.
Analysis of cytoplasmic and nuclear binding of [(3)H]aldosterone and [(3)H]spirolactone in rat kidneys.
Utilization of glycerol density gradients to evaluate sedimentation rates of receptor complexes.
Spirolactone inhibited aldosterone effects on urinary K(+):Na(+) ratios.
[(3)H]spirolactone did not form specific nuclear complexes unlike [(3)H]aldosterone.
Cytoplasmic binding of [(3)H]aldosterone sedimented at different rates based on salt concentration.

Abstract

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