O'Mahony, F., Toumi, F., Mroz, M. S., Welsby, Gail and Keely, S. J. (2008) Induction of Na+/K+/2Cl- cotransporter expression mediates chronic potentiation of intestinal epithelial Cl- secretion by EGF. AJP: Cell Physiology, 294 (6). C1362-C1370. ISSN 0363-6143
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Official URL: http://dx.doi.org/10.1152/ajpcell.00256.2007
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 μM) 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% of that in control cells (n = 21, P < 0.005). EGF-induced NKCC1 expression was abolished by actinomycin D, and RT-PCR analysis demonstrated EGF increased expression of NKCC1 mRNA. These data increase our understanding of mechanisms regulating intestinal fluid and electrolyte transport and reveal a novel role for the EGFR in the chronic regulation of epithelial secretory capacity through upregulation of NKCC1 expression.
|Uncontrolled Keywords (separate with ;):||epidermal growth factor; epithelium; chloride secretion; ion transport|
|Subjects:||B - Subjects allied to medicine > B230 - Pharmacy|
|Schools:||Faculty of Clinical & Biomedical Sciences > School of Pharmacy and Biomedical Sciences|
|Deposited By:||Carmit Erez|
|Deposited On:||21 Feb 2013 18:34|
|Last Modified:||28 Feb 2017 15:01|
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