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

1. In this study we used the short circuit current (I-SC) technique to meas ure the non-genomic effects of the female sex steroid 17 beta -oestradiol ( E-2) on electrogenic transepithelial ion transport in rat distal colonic ep ithelium. 2. Basal I-SC was largely composed of a transepithelial Cl- secretory compo nent with minimal electrogenic Na+ movement. E-2 (1-100 nM) caused a signif icant decrease in basal I-SC after 15 min. In addition, pre-treating coloni c 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- secr etion which was pre-stimulated by forskolin. Cl- secretory responses to the Ca2+-dependent secretagogue carbachol (10 muM) were also significantly red uced in the presence of E-2 (10-100 nM). However, E-2 had no effect on amil oride-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 produc ed 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 pa thway that involves intracellular Ca2+ and PKC. It is possible that this ge nder-specific mechanism contributes to the salt and water retention associa ted with high E-2 states.