Mineralocorticoid specificity of renal type I receptors: in vivo binding studies.
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.
D000450:Aldosterone / Q000378:metabolism; D000732:Androstanols / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003345:Corticosterone / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism*; D014156:Transcortin / Q000378:metabolism
D000732:Androstanols; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D014156:Transcortin; D003345:Corticosterone