Exclusion of corticosterone from epithelial mineralocorticoid receptors is insufficient for selectivity of aldosterone action: in vivo binding studies.
Adrenalectomized weanling rats injected with [3H]aldosterone plus excess RU486, with or without a range of doses of nonradioactive aldosterone or corticosterone, show tissue-specific patterns of competition for tracer binding to mineralocorticoid receptors (MR). From detailed dose-response curves, corticosterone in vivo shows approximately 3% the apparent affinity of aldosterone for MR in colon and kidney, approximately 30% for those in the heart, and approximately 300% in the hippocampus. We interpret these data as evidence that 1) relatively low levels of aldosterone cross the blood-brain barrier; and 2) specificity-conferring mechanisms in addition to the exclusion of corticosterone from epithelial MR are required for selective aldosterone action in sodium homeostasis.
Funder
J
J
Baker Medical Research Institute, Melbourne, Australia.
Myles
K
K
D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D003106:Colon / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D014886:Weaning
D006727:Hormone Antagonists; D018161:Receptors, Mineralocorticoid; D015735:Mifepristone; D000450:Aldosterone; D003345:Corticosterone