The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
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
Open accessAbstract
Mutations in human DRA cause congenital chloride diarrhea, thereby raising the possibility that it functions as a Cl(-)/HCO(3)(-) 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(-)/CHO(3)(-) exchange activity. Removal of extracellular Cl(-) from medium containing HCO(3)(-) caused a rapid intracellular alkalinization, whereas the intracellular pH increase following Cl(-) removal from HCO(3)(-)-free medium was reduced greater than 7-fold. The intracellular alkalinization in Cl(-)-free, HCO(3)(-)-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(-)/HCO(3)(-) 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.
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Mutations of the Down–regulated in adenoma (DRA) gene cause congenital chloride diarrhoea
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Sensors and regulators of intracellular pH
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The SLC26 gene family of anion transporters and channels
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Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCO3−Secretion
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Metadata
- Authors
- Melvin, J. E., Park, K., Richardson, L., Schultheis, P. J., & Shull, G. E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 274
- Issue
- 32
- Pages
- 22855-22861
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2051318454
- Cited by
- 275
- References
- 28
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Melvin, J. E., Park, K., Richardson, L., Schultheis, P. J., & Shull, G. E. (1999). 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. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.32.22855
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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