Regulation of endothelin-1 expression and function by nutrient stress in mouse colon epithelia.

Objective: The endothelin (ET) system is influenced by a variety of stress conditions in many tissues. However, the effects of nutrient stress conditions on ET expression and its function are not well understood in the intestinal tract, while ET-1 gene expression and peptide were found in the intestinal tract. The aim of this study was to investigate the effect of feeding and fasting on the expression of ET-1 and short-circuit current (Isc) induced by ET-1 in mouse colon.

Material And Methods: Mice were fed freely, fasted for 48 h, and re-fed after fasting, respectively. ET-1 mRNA levels and peptide concentrations were analyzed using real-time polymerase chain reaction (PCR) and sandwich ELISA, respectively. Isc of epithelial tissue was measured under short-circuit conditions using a Ussing chamber.

Results: ET-1 mRNA expression and peptide concentrations in epithelial colonic tissue were significantly increased 48 h after fasting, and decreased within 2 h of re-feeding after a 48-h fast. Furthermore, the addition of ET-1 to the serosal but not the mucosal side increased Isc in colonic epithelia. An increase in Isc was caused by chloride ion (Cl(-)) secretion because Isc induced by ET-1 was blocked by bumetanide and Cl(- -) free conditions. In addition, an increase in Isc induced by ET-1 in colon excised from fasted mice was much lower than that obtained from free-fed mice.

Conclusions: Gene expression, peptide concentration, and the function of ET-1 in mouse colonic epithelia are regulated by nutrient stress.