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Am J Physiol Endocrinol Metab 252: E224-E229, 1987;
0193-1849/87 $5.00
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AJP - Endocrinology and Metabolism, Vol 252, Issue 2 E224-E229, Copyright © 1987 by American Physiological Society

ARTICLES

Mineralocorticoid specificity of renal type I receptors: in vivo binding studies

K. Sheppard and J. W. Funder

We have injected rats with [3H]aldosterone or [3H]corticosterone, plus 100-fold excess of the highly specific glucocorticoid RU 28362, with or without excess unlabeled aldosterone or corticosterone and compared type I receptor occupancy in kidney and hippocampus. Thirty minutes after subcutaneous injection [3H]aldosterone was well retained in renal papilla-inner medulla, renal cortex-outer medulla, and hippocampus; in contrast, [3H]corticosterone was well retained only in hippocampus. Competition studies for [3H]aldosterone binding sites showed corticosterone to be a poor competitor in the kidney compared with hippocampus. Time-course studies, with rats killed 10-180 min after tracer administration, showed very low uptake/retention of [3H]corticosterone by kidney; in hippocampus [3H]corticosterone retention was similar to that of [3H]aldosterone in kidney, and retention of [3H]aldosterone by hippocampus was much more prolonged than of either tracer in any other tissue. Studies in 10-day-old rats, with very low levels of corticosteroid binding globulin (CBG), showed a high degree of aldosterone selectivity in both zones of the kidney, whereas [3H]aldosterone and [3H]corticosterone were equivalently bound in hippocampus. We interpret these data as evidence for a mechanism unrelated to extravascular CBG conferring mineralocorticoid specificity on renal type I receptors and propose two models derived from our findings consistent with such differential selectivity.


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