title: Nongenomic aldosterone effects: the cell membrane as a specific target of mineralocorticoid action.
abstract: Studies in extrarenal, nonepithelial cells such as human lymphocytes and smooth muscle cells indicate that aldosterone produces not only delayed genomic effects, but also rapid, non-genomic effects on transmembrane electrolyte movements. These non-genomic events involve the immediate activation of the sodium/proton-exchanger of the cell membrane at very low, physiological concentrations of aldosterone in both lymphocytes and cultured rat vascular smooth muscle cells. This new pathway for mineralocorticoid action is further characterized by a 10,000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones, classical mineralocorticoid antagonists, as antagonists of the response. Aldosterone-specific binding sites have been demonstrated in the plasma membrane of human lymphocytes, with features identical to those seen for the rapid aldosterone effects in the same cells. As second messenger the inositol-1,4,5-trisphosphate pathway has been identified both in human lymphocytes and vascular smooth muscle cells, which respond over the same rapid time course. In addition, the aldosterone effect on inositol-1,4,5-trisphosphate production in vascular smooth muscle cells is sensitive to pertussis toxin, but not to cholera toxin, pointing to a possible involvement of G-proteins in the cellular signalling. This article reviews the data supporting a new, two-step model for successive non-genomic and genomic mineralocorticoid effects.
authors.affiliation: Baker Medical Research Institute, Prahran, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Wehling
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004573:Electrolytes / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D004573:Electrolytes; D000450:Aldosterone