Upregulation of Intestinal NHE3 Following Saline Ingestion

Abstract

Background: Little is known about the effect of salt content of ingested fluid on intestinal transport processes. Osmosensitive genes include the serum- and glucocorticoid-inducible kinase SGK1, which is up-regulated by hyperosmolarity and cell shrinkage. SGK1 is in turn a powerful stimulator of the intestinal Na⁺/H⁺ exchanger NHE3. The present study was thus performed to elucidate, whether the NaCl content of beverages influences NHE3 activity. Methods: Mice were offered access to either plain water or isotonic saline ad libitum. NHE3 transcript levels and protein abundance in intestinal tissue were determined by confocal immunofluorescent microscopy, RT-PCR and western blotting, cytosolic pH (pH_i) in intestinal cells from 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence and Na⁺/H⁺ exchanger activity from the Na⁺ dependent realkalinization following an ammonium pulse. Results: Saline drinking significantly enhanced fluid intake and increased NHE3 transcript levels, NHE3 protein and Na⁺/H⁺ exchanger activity. Conclusions: Salt content of ingested fluid has a profound effect on intestinal Na⁺/H⁺ exchanger expression and activity.