Rapid Effects of Aldosterone on Sodium-Hydrogen Exchange in Isolated Colonic Crypts |
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Authors: | DC Winter MF Schneider GC O'Sullivan BJ Harvey JP Geibel |
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Institution: | (1) Department of Surgery, Yale University, 310 Cedar Street, BML 265, New Haven, CT 06510-8026, USA, US;(2) Department of Cellular and Molecular Physiology, Yale University, 310 Cedar Street, BML, New Haven, CT 06510-8026, USA, US;(3) Wellcome Trust Cellular Physiology Research Unit, Department of Physiology, University College, Cork, Ireland, IE;(4) Department of Surgery, Mercy Hospital, National University of Ireland, Cork, Ireland, IE |
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Abstract: | Aldosterone plays a central role in the homeostatic regulation of extracellular fluid volume by stimulating transepithelial
electrolyte transport. These effects involve binding to an intracellular receptor, modification of genomic events and protein
synthesis. Rapid cellular responses to steroid hormones have been observed in a variety of nonepithelial tissues. The term
``nongenomic' has been proposed for these fast steroid responses since they are unaffected by inhibitors of protein synthesis.
We hypothesized that colonic crypts, recently demonstrated to absorb fluid, would respond rapidly to aldosterone.
Cytoplasmic pH changes in crypts loaded with a pH-sensitive, fluorescent dye (BCECF) were recorded with confocal laser imaging.
An intracellular alkalization of colonic crypts was observed within one minute of aldosterone application that was inhibited
by ethylisopropylamiloride or the absence of extracellular sodium, yet unaffected by inhibitors of protein synthesis. The
genesis of this rapid and distinct steroid action involves a signal transduction pathway that involves G proteins, protein
kinase C, and prostaglandins.
We have identified, by real-time imaging, a nongenomic upregulation of sodium-hydrogen exchange in colonic crypts by aldosterone
that occurs independent of the traditional receptor. This distinct, rapid onset effect of aldosterone on epithelial ion transport
has major implications for our understanding of fluid and electrolyte homeostasis in health and disease.
Received: 27 October 1998/Revised: 23 March 1999 |
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Keywords: | : Steroid — Sodium-hydrogen exchange — Prostaglandins — Protein kinase C |
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