17β-Oestradiol acutely regulates Cl− secretion in rat distal colonic epithelium

摘要

In this study we used the short circuit current (ISC) technique to measure the non-genomic effects of the female sex steroid 17β-oestradiol (E2) on electrogenic transepithelial ion transport in rat distal colonic epithelium.Basal ISC was largely composed of a transepithelial Cl− secretory component with minimal electrogenic Na+ movement. E2 (1-100 nm) caused a significant decrease in basal ISC after 15 min. In addition, pre-treating colonic epithelial tissues with E2 (0.1-100 nm) for 10 min significantly reduced forskolin (20 μm)-induced Cl− secretion. E2 also down-regulated Cl− secretion which was pre-stimulated by forskolin. Cl− secretory responses to the Ca2+-dependent secretagogue carbachol (10 μm) were also significantly reduced in the presence of E2 (10- 100 nm). However, E2 had no effect on amiloride-sensitive Na+ absorption.The rapid anti-secretory effect of E2 was abolished in the presence of the intracellular Ca2+ chelator BAPTA (50 μm) or the protein kinase C (PKC) inhibitor chelerythrine chloride (1 μm). However, in the presence of the nuclear oestrogen receptor antagonist tamoxifen (10 μm), E2 still produced an inhibition of Cl− secretion. Testosterone, progesterone and 17α-oestradiol had no significant effect on colonic Cl− secretion. Also, E2 (100 nm) did not alter Cl− secretion in colonic epithelia isolated from male rats.We conclude that E2 inhibits colonic Cl− secretion via a non-genomic pathway that involves intracellular Ca2+ and PKC. It is possible that this gender-specific mechanism contributes to the salt and water retention associated with high E2 states.