Specific nongenomic actions of aldosterone.
BACKGROUND
According to the traditional model, steroid hormones modulate gene transcription and protein synthesis. The considerable latency of these genomic steroid effects is the consequence of these time-consuming steps of action. Over the years, it has become increasingly clear that rapid actions of steroids exist that are incompatible with this "classic" genomic model of action. These rapid, nongenomic effects, which recently have been shown for virtually all groups of steroids, are likely to be transmitted by specific membrane receptors.


METHODS
A review of data mainly focusing on the nongenomic in vitro and in vivo effects of aldosterone is presented.


RESULTS
For rapid aldosterone effects, a prominent example of a receptor/effector cascade for nongenomic steroid effects has been described in various cell types. Nonclassic membrane receptors with a high affinity for aldosterone, but not for cortisol, seem to be involved. As an important second messenger, [Ca2+]i is consistently increased within minutes after the addition of aldosterone. The effects are half maximal at physiological concentrations of free aldosterone (approximately 0.1 nmol/L), while the classic mineralocorticoid antagonist canrenone is ineffective in blocking the action of aldosterone. In addition, cortisol is active only at supramicromolar concentrations. Aldosterone rapidly acts on further cell signaling systems, for example, phosphoinositide hydrolysis and cAMP generation.


CONCLUSIONS
For a better understanding of nongenomic aldosterone action even in a clinical context, future research will have to target the cloning of the first membrane receptor for aldosterone and the evaluation of the clinical relevance of rapid steroid effects in general.
Falkenstein
E
E
Institute of Clinical Pharmacology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
Christ
M
M
Feuring
M
M
Wehling
M
M
D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D016678:Genome; D006801:Humans; D008566:Membranes / Q000378:metabolism
D000450:Aldosterone