Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.

Hdl Handle:
http://hdl.handle.net/10147/132289
Title:
Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.
Authors:
Alzamora, Rodrigo; O'Mahony, Fiona; Harvey, Brian J
Affiliation:
Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland.
Citation:
Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon. 2011:notSteroids
Journal:
Steroids
Issue Date:
8-May-2011
URI:
http://hdl.handle.net/10147/132289
DOI:
10.1016/j.steroids.2011.04.016
PubMed ID:
21600231
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/21600231
Abstract:
Excessive Cl(-) secretion is the driving force for secretory diarrhea. 17β-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17β-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17β-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. 17β-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. 17β-Estradiol responses were insensitive to the pure anti-estrogen ICI 182,720. 17β-Estradiol exerted its effects downstream of enterotoxin-induced production of second messengers (cAMP and cGMP) but was dependent on PKCδ activation. In nystatin-permeabilized tissues, apical Cl(-) currents were unaffected by 17β-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, 17β-estradiol inhibits enterotoxin-induced Cl(-) secretion via a PKCδ-dependent mechanism involving inhibition of basolateral KCNQ1 channels. These data elucidate mechanisms of 17β-estradiol inhibition of Cl(-) secretion induced by enterotoxins in intestinal epithelia, which may be relevant for the treatment of diarrheal diseases.
Item Type:
Article
Language:
en
ISSN:
1878-5867

Full metadata record

DC FieldValue Language
dc.contributor.authorAlzamora, Rodrigoen
dc.contributor.authorO'Mahony, Fionaen
dc.contributor.authorHarvey, Brian Jen
dc.date.accessioned2011-05-27T14:50:02Z-
dc.date.available2011-05-27T14:50:02Z-
dc.date.issued2011-05-08-
dc.identifier.citationEstrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon. 2011:notSteroidsen
dc.identifier.issn1878-5867-
dc.identifier.pmid21600231-
dc.identifier.doi10.1016/j.steroids.2011.04.016-
dc.identifier.urihttp://hdl.handle.net/10147/132289-
dc.description.abstractExcessive Cl(-) secretion is the driving force for secretory diarrhea. 17β-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17β-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17β-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. 17β-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. 17β-Estradiol responses were insensitive to the pure anti-estrogen ICI 182,720. 17β-Estradiol exerted its effects downstream of enterotoxin-induced production of second messengers (cAMP and cGMP) but was dependent on PKCδ activation. In nystatin-permeabilized tissues, apical Cl(-) currents were unaffected by 17β-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, 17β-estradiol inhibits enterotoxin-induced Cl(-) secretion via a PKCδ-dependent mechanism involving inhibition of basolateral KCNQ1 channels. These data elucidate mechanisms of 17β-estradiol inhibition of Cl(-) secretion induced by enterotoxins in intestinal epithelia, which may be relevant for the treatment of diarrheal diseases.-
dc.languageENG-
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/21600231en
dc.titleEstrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.en
dc.typeArticleen
dc.contributor.departmentDepartment of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland.en
dc.identifier.journalSteroidsen
dc.description.provinceLeinster-

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.