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Am J Physiol Renal Physiol 293: F1571-F1576, 2007. First published August 15, 2007; doi:10.1152/ajprenal.00132.2007
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Hydrogen peroxide stimulates chloride secretion in primary inner medullary collecting duct cells via mPGES-1-derived PGE2

Sunhapas Soodvilai, Zhanjun Jia, and Tianxin Yang

Department of Internal Medicine, University of Utah, and Veterans Affairs Medical Center, Salt Lake City, Utah

Submitted 20 March 2007 ; accepted in final form 30 July 2007

We investigated the role and mechanism of H2O2 in regulation of NaCl transport in primary inner medullary collecting duct (IMCD) cells. IMCD cells were isolated from wild-type mice and grown onto semipermeable membranes, and short-circuit current (Isc) was determined by Ussing chamber. Exposure of IMCD cells to H2O2 at a range of 100–300 µM caused a rapid increase in Isc in a time- and dose-dependent manner. This increase was almost abolished by the cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel inhibitors diphenylamine-2-carboxylic acid (DPC) and CFTRinhibitor-172. In contrast, the magnitude of stimulation was unaffected by the epithelial Na+ channel (ENaC) inhibitor amiloride. The H2O2-induced Cl secretion was significantly inhibited by indomethacin, as well as by microsomal PGE synthase-1 (mPGES-1) deficiency. Like H2O2, PGE2 treatment induced a twofold increase in Isc that was reduced by the protein kinase A (PKA) inhibitors H-89 and KT5720. These data suggest that H2O2 stimulates CFTR Cl channel-mediated Cl secretion through cyclooxygenase- and mPGES-1-dependent release of PGE2 and subsequent activation of PKA.

hydrogen peroxide; microsomal prostaglandin E synthase-1; cystic fibrosis transmembrane conductance regulator



Address for reprint requests and other correspondence: T. Yang, Univ. of Utah and Veterans Affairs Medical Center, 30 N. 1900 E., Rm. 4R312, Salt Lake City, UT 84132 (e-mail: tianxin.yang{at}hsc.utah.edu)




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Am. J. Physiol. Renal Physiol.Home page
Z. Jia, H. Wang, and T. Yang
Mice lacking mPGES-1 are resistant to lithium-induced polyuria
Am J Physiol Renal Physiol, December 1, 2009; 297(6): F1689 - F1696.
[Abstract] [Full Text] [PDF]




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