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J Biol Chem, Vol. 274, Issue 32, 22855-22861, August 6, 1999
From the Mutations in human DRA cause congenital chloride
diarrhea, thereby raising the possibility that it functions as a
Cl
Mouse Down-regulated in Adenoma (DRA) Is an Intestinal
Cl
/HCO3 Exchanger and Is Up-regulated
in Colon of Mice Lacking the NHE3 Na+/H+
Exchanger
,,, Center for Oral Biology, University of
Rochester School of Medicine and Dentistry, Rochester, New York 14642 and the § Department of Molecular Genetics, Biochemistry and
Microbiology, University of Cincinnati College of Medicine, Cincinnati,
Ohio 45267-0524
/HCO3 exchanger. To test this
hypothesis we cloned a cDNA encoding mouse DRA (mDRA) and analyzed
its activity in cultured mammalian cells. When expressed in HEK 293 cells, mDRA conferred Na+-independent, electroneutral
Cl/CHO3 exchange activity. Removal of
extracellular Cl from medium containing
HCO3 caused a rapid intracellular alkalinization,
whereas the intracellular pH increase following Cl
removal from HCO3-free medium was reduced greater
than 7-fold. The intracellular alkalinization in Cl-free,
HCO3-containing medium was unaffected by removal of
extracellular Na+ or by depolarization of the membrane by
addition of 75 mM K+ to the medium. Like human
DRA mRNA, mDRA transcripts were expressed at high levels in cecum
and colon and at lower levels in small intestine. The expression of
mDRA mRNA was modestly up-regulated in the colon of mice lacking
the NHE3 Na+/H+ exchanger. These results show
that DRA is a Cl/HCO3 exchanger and
suggest that it normally acts in concert with NHE3 to absorb NaCl and
that in NHE3-deficient mice its activity is coupled with those of the
sharply up-regulated colonic H+,K+-ATPase and
epithelial Na+ channel to mediate electrolyte and fluid absorption.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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M. Soleimani, T. Greeley, S. Petrovic, Z. Wang, H. Amlal, P. Kopp, and C. E. Burnham Pendrin: an apical Cl{-}/OH{-}/HCO3{-} exchanger in the kidney cortex Am J Physiol Renal Physiol, February 1, 2001; 280(2): F356 - F364. [Abstract] [Full Text] [PDF]
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V. M. Rajendran, J. Black, T. A. Ardito, P. Sangan, S. L. Alper, C. Schweinfest, M. Kashgarian, and H. J. Binder Regulation of DRA and AE1 in rat colon by dietary Na depletion Am J Physiol Gastrointest Liver Physiol, November 1, 2000; 279(5): G931 - G942. [Abstract] [Full Text] [PDF]
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L. L. Clarke, M. C. Harline, L. R. Gawenis, N. M. Walker, J. T. Turner, and G. A. Weisman Extracellular UTP stimulates electrogenic bicarbonate secretion across CFTR knockout gallbladder epithelium Am J Physiol Gastrointest Liver Physiol, July 1, 2000; 279(1): G132 - G138. [Abstract] [Full Text] [PDF]
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V. J. Wheat, H. Shumaker, C. Burnham, G. E. Shull, J. R. Yankaskas, and M. Soleimani CFTR induces the expression of DRA along with Cl-/HCO3- exchange activity in tracheal epithelial cells Am J Physiol Cell Physiol, July 1, 2000; 279(1): C62 - C71. [Abstract] [Full Text] [PDF]
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G. E. Shull, M. L. Miller, and P. J. Schultheis Lessons from Genetically Engineered Animal Models. VIII. Absorption and secretion of ions in the gastrointestinal tract Am J Physiol Gastrointest Liver Physiol, February 1, 2000; 278(2): G185 - G190. [Abstract] [Full Text] [PDF]
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R. L. Evans, K. Park, R. J. Turner, G. E. Watson, H.-V. Nguyen, M. R. Dennett, A. R. Hand, M. Flagella, G. E. Shull, and J. E. Melvin Severe Impairment of Salivation in Na+/K+/2Cl- Cotransporter (NKCC1)-deficient Mice J. Biol. Chem., August 25, 2000; 275(35): 26720 - 26726. [Abstract] [Full Text] [PDF]
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Z. Wang, S. Petrovic, E. Mann, and M. Soleimani Identification of an apical Cl-/HCO3- exchanger in the small intestine Am J Physiol Gastrointest Liver Physiol, March 1, 2002; 282(3): G573 - G579. [Abstract] [Full Text] [PDF]
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