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

Hdl Handle:
http://hdl.handle.net/10147/207084
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:
Steroids. 2011 Aug;76(9):867-76. Epub 2011 May 8.
Journal:
Steroids
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207084
DOI:
10.1016/j.steroids.2011.04.016
PubMed ID:
21600231
Abstract:
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:
eng
MeSH:
8-Bromo Cyclic Adenosine Monophosphate/pharmacology; Androgens/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
ISSN:
1878-5867 (Electronic); 0039-128X (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorAlzamora, Rodrigoen_GB
dc.contributor.authorO'Mahony, Fionaen_GB
dc.contributor.authorHarvey, Brian Jen_GB
dc.date.accessioned2012-02-01T09:58:49Z-
dc.date.available2012-02-01T09:58:49Z-
dc.date.issued2012-02-01T09:58:49Z-
dc.identifier.citationSteroids. 2011 Aug;76(9):867-76. Epub 2011 May 8.en_GB
dc.identifier.issn1878-5867 (Electronic)en_GB
dc.identifier.issn0039-128X (Linking)en_GB
dc.identifier.pmid21600231en_GB
dc.identifier.doi10.1016/j.steroids.2011.04.016en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207084-
dc.description.abstractExcessive 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.en_GB
dc.language.isoengen_GB
dc.subject.mesh8-Bromo Cyclic Adenosine Monophosphate/pharmacologyen_GB
dc.subject.meshAndrogens/pharmacology/physiologyen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBacterial Toxins/*pharmacologyen_GB
dc.subject.meshChloride Channels/metabolismen_GB
dc.subject.meshChlorides/*metabolismen_GB
dc.subject.meshCholera Toxin/*pharmacologyen_GB
dc.subject.meshColon/cytology/drug effects/*metabolismen_GB
dc.subject.meshCyclic GMP/analogs & derivatives/pharmacologyen_GB
dc.subject.meshEnterotoxins/*pharmacologyen_GB
dc.subject.meshEnzyme Activationen_GB
dc.subject.meshEpithelium/drug effects/metabolismen_GB
dc.subject.mesh*Escherichia colien_GB
dc.subject.meshEstradiol/*pharmacology/physiologyen_GB
dc.subject.meshEstrogens/*pharmacology/physiologyen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshKCNQ1 Potassium Channel/metabolismen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMembrane Potentials/drug effectsen_GB
dc.subject.meshProgesterone/pharmacology/physiologyen_GB
dc.subject.meshProgestins/pharmacology/physiologyen_GB
dc.subject.meshProtein Kinase C-delta/metabolismen_GB
dc.subject.meshRatsen_GB
dc.subject.meshRats, Sprague-Dawleyen_GB
dc.subject.meshTestosterone/pharmacology/physiologyen_GB
dc.titleEstrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.en_GB
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_GB
dc.identifier.journalSteroidsen_GB
dc.description.provinceLeinster-

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