Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Affiliation
Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education, and Research Centre, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland.Issue Date
2012-02-01T09:58:49ZMeSH
8-Bromo Cyclic Adenosine Monophosphate/pharmacologyAndrogens/pharmacology/physiology
Animals
Bacterial Toxins/*pharmacology
Chloride Channels/metabolism
Chlorides/*metabolism
Cholera Toxin/*pharmacology
Colon/cytology/drug effects/*metabolism
Cyclic GMP/analogs & derivatives/pharmacology
Enterotoxins/*pharmacology
Enzyme Activation
Epithelium/drug effects/metabolism
*Escherichia coli
Estradiol/*pharmacology/physiology
Estrogens/*pharmacology/physiology
Female
KCNQ1 Potassium Channel/metabolism
Male
Membrane Potentials/drug effects
Progesterone/pharmacology/physiology
Progestins/pharmacology/physiology
Protein Kinase C-delta/metabolism
Rats
Rats, Sprague-Dawley
Testosterone/pharmacology/physiology
Metadata
Show full item recordCitation
Steroids. 2011 Aug;76(9):867-76. Epub 2011 May 8.Journal
SteroidsDOI
10.1016/j.steroids.2011.04.016PubMed ID
21600231Abstract
Excessive Cl(-) secretion is the driving force for secretory diarrhea. 17beta-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17beta-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17beta-estradiol on cholera toxin and heat-stable enterotoxin induced Cl(-) secretion in rat colonic mucosal sheets was studied by current-voltage clamping. Selective permeabilization of apical or basolateral membranes with amphotericin B or nystatin was used to isolate basolateral K(+) channel and apical Cl(-) channel activity, respectively. 17beta-Estradiol dose-dependently inhibited secretory responses to both toxins with IC(50) values of approximately 1nM. This effect was female-gender specific, with no inhibition observed in male tissues. 17beta-Estradiol responses were insensitive to the pure anti-estrogen ICI 182,720. 17beta-Estradiol exerted its effects downstream of enterotoxin-induced production of second messengers (cAMP and cGMP) but was dependent on PKCdelta activation. In nystatin-permeabilized tissues, apical Cl(-) currents were unaffected by 17beta-estradiol treatment while basolateral K(+) current was profoundly inhibited by the hormone. This current was sensitive to the specific KCNQ1 channel inhibitors chromanol 293B and HMR-1556. In conclusion, 17beta-estradiol inhibits enterotoxin-induced Cl(-) secretion via a PKCdelta-dependent mechanism involving inhibition of basolateral KCNQ1 channels. These data elucidate mechanisms of 17beta-estradiol inhibition of Cl(-) secretion induced by enterotoxins in intestinal epithelia, which may be relevant for the treatment of diarrheal diseases.Language
engISSN
1878-5867 (Electronic)0039-128X (Linking)
ae974a485f413a2113503eed53cd6c53
10.1016/j.steroids.2011.04.016
Scopus Count
Collections
Related articles
- Traditional Chinese formula, lubricating gut pill, stimulates cAMP-dependent CI(−) secretion across rat distal colonic mucosa.
- Authors: Wu D, Zhou J, Wang X, Cui B, An R, Shi H, Yuan J, Hu Z
- Issue date: 2011 Mar 24
- Female gender-specific inhibition of KCNQ1 channels and chloride secretion by 17beta-estradiol in rat distal colonic crypts.
- Authors: O'Mahony F, Alzamora R, Betts V, LaPaix F, Carter D, Irnaten M, Harvey BJ
- Issue date: 2007 Aug 24
- Sex and estrous cycle-dependent rapid protein kinase signaling actions of estrogen in distal colonic cells.
- Authors: O'Mahony F, Harvey BJ
- Issue date: 2008 Oct
- Berberine inhibition of electrogenic ion transport in rat colon.
- Authors: Taylor CT, Baird AW
- Issue date: 1995 Nov
- Rutaecarpine induces chloride secretion across rat isolated distal colon.
- Authors: Wu D, Hu Z
- Issue date: 2008 Apr