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

Journal Article · · Am. J. Physiol.; (United States)
OSTI ID:6284330
;

The authors have injected rats with (TH)aldosterone or (TH) 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 (TH)aldosterone was well retained in renal papilla-inner medulla, renal cortex-outer medulla, and hippocampus; in contrast, (TH)corticosterone was well retained only in hippocampus. Competition studies for (TH)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 (TH)corticosterone by kidney; in hippocampus (TH)corticosterone retention was similar to that of (TH)aldosterone in kidney, and retention of (TH)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 9TH)aldosterone and (TH)corticosterone were equivalently bound in hippocampus. They interpret these data as evidenced for a mechanism unrelated to extravascular CBG conferring mineralocorticoid specificity on renal type I receptors and propose two models derived from their findings consistent with such differential selectivity.

Research Organization:
Prince Henry's Hospital, Victoria, Australia
OSTI ID:
6284330
Journal Information:
Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 252:2; ISSN AJPHA
Country of Publication:
United States
Language:
English

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Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ALDEHYDES
ALDOSTERONE
ANIMALS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
CORTICOSTEROIDS
CORTICOSTERONE
DISTRIBUTION
GLUCOCORTICOIDS
HIPPOCAMPUS
HORMONES
HYDROXY COMPOUNDS
IN VIVO
KETONES
KIDNEYS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MINERALOCORTICOIDS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PREGNANES
RATS
RETENTION
RODENTS
SEPARATION PROCESSES
STEROID HORMONES
STEROIDS
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS
VERTEBRATES