Rapid effects of aldosterone on sodium-hydrogen exchange in isolated colonic crypts

Aldosterone plays a central role in the homeostatic regulation of extracell ular fluid volume by stimulating transepithelial electrolyte transport. The se effects involve binding to an intracellular receptor, modification of ge nomic events and protein synthesis. Rapid cellular responses to steroid hor mones have been observed in a variety of nonepithelial tissues. The term "n ongenomic" has been proposed for these fast steroid responses since they ar e unaffected by inhibitors of protein synthesis. We hypothesized that colon ic crypts, recently demonstrated to absorb fluid, would respond rapidly to aldosterone. Cytoplasmic pH changes in crypts loaded with a pH-sensitive, fluorescent dy e (BCECF) were recorded with confocal laser imaging. An intracellular alkal ization of colonic crypts was observed within one minute of aldosterone app lication that was inhibited by ethylisopropylamiloride or the absence of ex tracellular sodium, yet unaffected by inhibitors of protein synthesis. The genesis of this rapid and distinct steroid action involves a signal transdu ction pathway that involves G proteins, protein kinase C, and prostaglandin s. We have identified, by real-time imaging, a nongenomic upregulation of sodi um-hydrogen exchange in colonic crypts by aldosterone that occurs independe nt of the traditional receptor. This distinct, rapid onset effect of aldost erone on epithelial ion transport has major implications for our understand ing of fluid and electrolyte homeostasis in health and disease.