Rapid effects of aldosterone on sodium-hydrogen exchange in isolated colonic crypts.
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.
Department of Surgery, Yale University, 310 Cedar Street, BML 265, New Haven, CT 06510-8026, USA.
D C
DC
Winter
M F
MF
Schneider
G C
GC
O'Sullivan
B J
BJ
Harvey
J P
JP
Geibel
D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D001639:Bicarbonates / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D005110:Extracellular Space; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007474:Ion Exchange; D017136:Ion Transport / Q000187:drug effects; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010740:Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects*; D013148:Spironolactone / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D001639:Bicarbonates; D004232:Diuretics; D005452:Fluoresceins; D005456:Fluorescent Dyes; D020024:Leukotriene Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D011448:Prostaglandin Antagonists; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D017923:Sodium-Hydrogen Exchangers; D013148:Spironolactone; D016718:Arachidonic Acid; D000450:Aldosterone; D000584:Amiloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D012964:Sodium; D011494:Protein Kinases; D010740:Phospholipases; C039614:ethylisopropylamiloride