Induction of Na+/K+/2Cl- cotransporter expression mediates chronic potentiation of intestinal epithelial Cl- secretion by EGF

American Journal of Physiology. Cell Physiology
Fiona O'MahonyStephen J Keely

Abstract

Alterations in EGF receptor (EGFR) signaling occur in intestinal disorders associated with dysregulated epithelial transport. In the present study, we investigated a role for the EGFR in the chronic regulation of intestinal epithelial secretory function. Epithelial Cl(-) secretion was measured as changes in short-circuit current (Isc) across voltage-clamped monolayers of T84 cells in Ussing chambers. Acute treatment of T84 cells with EGF (100 ng/ml, 15 min) chronically enhanced Isc responses to a broad range of secretagogues. This effect was apparent within 3 h, maximal by 6 h, and sustained for 24 h after treatment with EGF. The Na+/K+/2Cl(-) cotransporter (NKCC1) inhibitor bumetanide (100 microM) abolished the effect of EGF, indicating increased responses are due to potentiated Cl(-) secretion. Neither basal nor agonist-stimulated levels of intracellular Ca2+ or PKA activity were altered by EGF, implying that the effects of the growth factor are not due to chronic alterations in levels of second messengers. EGF increased the expression of NKCC1 with a time course similar to that of its effects on Cl(-) secretion. This effect of EGF was maximal after 6 h, at which time NKCC1 expression in EGF-treated cells was 199.9 +/- 21.9% ...Continue Reading

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Citations

Oct 8, 2013·Pflügers Archiv : European journal of physiology·Nicolas Markadieu, Eric Delpire
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Feb 12, 2014·Seminars in Cell & Developmental Biology·Fenghua Zeng, Raymond C Harris
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Jan 24, 2019·Mediators of Inflammation·Sandra Rayego-MateosMarta Ruiz-Ortega
Mar 26, 2010·Metabolic Brain Disease·Arumugam R Jayakumar, Michael D Norenberg
Apr 15, 2018·Molecular Cancer Therapeutics·Annie MoisanCéline Adessi

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