title: 17beta-oestradiol acutely regulates Cl- secretion in rat distal colonic epithelium.
abstract: In this study we used the short circuit current (ISC) technique to measure the non-genomic effects of the female sex steroid 17beta-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 microM)-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 microM) 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 microM) or the protein kinase C (PKC) inhibitor chelerythrine chloride (1 microM). However, in the presence of the nuclear oestrogen receptor antagonist tamoxifen (10 microM), E2 still produced an inhibition of Cl- secretion. Testosterone, progesterone and 17alpha-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.
authors.affiliation: Wellcome Trust Cellular Physiology Research Unit, Physiology Department, University College Cork, Ireland. mdpy6009@bureau.ucc.ie
authors.forename: S B
authors.initials: SB
authors.lastname: Condliffe
authors.forename: C M
authors.initials: CM
authors.lastname: Doolan
authors.forename: B J
authors.initials: BJ
authors.lastname: Harvey
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000201:enzymology / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D002712:Chlorides; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D018721:Muscarinic Agonists; D013629:Tamoxifen; D005576:Colforsin; D004958:Estradiol; D004533:Egtazic Acid; D002217:Carbachol; D012964:Sodium; D011493:Protein Kinase C; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid