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Estrogen inhibits chloride secretion caused by cholera and Escher.pdf (611.5 kB)

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

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Version 2 2022-07-29, 11:16
Version 1 2019-11-22, 16:42
journal contribution
posted on 2019-11-22, 16:42 authored by Rodrigo Alzamora, Fiona O'Mahony, Brian J. Harvey

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.

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This article is also available at http://www.sciencedirect.com/science/article/pii/S0039128X11001619

Published Citation

Alzamora R, O'Mahony F, Harvey BJ. Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon. Steroids. 2011;76(9):867-76.

Publication Date

2011-08-01

PubMed ID

21600231

Department/Unit

  • Beaumont Hospital
  • Molecular Medicine