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

We have injected rats with 3Haldosterone or 3Hcorticosterone, 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 3Haldosterone was well retained in renal papilla-inner medulla, renal cortex-outer medulla, and hippocampus; in contrast, 3Hcorticosterone was well retained only in hippocampus. Competition studies for 3Haldosterone 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 3Hcorticosterone by kidney; in hippocampus 3Hcorticosterone retention was similar to that of 3Haldosterone in kidney, and retention of 3Haldosterone 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 3Haldosterone and 3Hcorticosterone 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.