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

1. In this study we used the short circuit current (I-SC) technique to measure the non-genomic effects of the female sex steroid 17 beta -oestradiol (E-2) on electrogenic transepithelial ion transport in rat distal colonic epithelium. 2. Basal I-SC was largely composed of a transepithelial Cl- secretory component with minimal electrogenic Na+ movement. E-2 (1-100 nM) caused a significant decrease in basal I-SC after 15 min. In addition, pre-treating colonic epithelial tissues with E-2 (0.1-100 nM) for 10 min significantly reduced forskolin (20 muM)-induced Cl- secretion. E-2 also down-regulated Cl- secretion which was pre-stimulated by forskolin. Cl- secretory responses to the Ca2+-dependent secretagogue carbachol (10 muM) were also significantly reduced in the presence of E-2 (10-100 nM). However, E-2 had no effect on amiloride-sensitive Na+ absorption. 3. The rapid anti-secretory effect of E-2 was abolished in the presence of the intracellular Ca2+ chelator BAPTA (50 muM) or the protein kinase C (PKC) inhibitor chelerythrine chloride (1 muM). However, in the presence of the nuclear oestrogen receptor antagonist tamoxifen (10 muM), E-2 still produced an inhibition of Cl- secretion. Testosterone, progesterone and 17 alpha -oestradiol had no significant effect on colonic Cl- secretion. Also, E-2 (100 nM) did not alter Cl- secretion in colonic epithelia isolated from male rats. 4. We conclude that E-2 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 E-2 states.