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Functional coupling of the downregulated in adenoma Cl−/base exchanger DRA and the apical Na+/H+exchangers NHE2 and NHE3
- Source :
- American Journal of Physiology-Gastrointestinal and Liver Physiology. 296:G202-G210
- Publication Year :
- 2009
- Publisher :
- American Physiological Society, 2009.
-
Abstract
- Non-nutrient-dependent salt absorption across the brush-border membrane of intestinal epithelial cells is primarily mediated by coupled apical Na+/H+(aNHE) and anion exchange transport, with the latter suspected of being mediated by DRA (downregulated in adenoma; SLC26A3) that is defective in congenital chloridorrhea. To investigate DRA in greater detail and determine whether DRA and NHE activities can be coupled, we measured22Na+and36Cl−uptake in Caco2BBE colon cells infected with the tet-off-inducible DRA transgene. Under basal conditions, DRA activity was low in normal and infected Caco2BBE cells in the presence of tetracycline, whereas NHE activities could be easily detected. When apical NHE activity was increased by transfection or serum-induced expression of the aNHE isoforms NHE2 and NHE3, increased36Cl−uptake was observed. Inhibition of DRA activity by niflumic acid was greater than that by DIDS as well as by the NHE inhibitor dimethylamiloride and the carbonic anhydrase inhibitor methazolamide. DRA activity was largely aNHE-dependent, whereas a component of DRA-independent aNHE uptake continued to be observed. Coupled aNHE and DRA activities were inhibited by increased cellular cAMP and calcium and were associated with synaptotagmin I-dependent, clathrin-mediated endocytosis. In summary, these data support the role of DRA in electroneutral NaCl absorption involving functional coupling of Cl−/base exchange and apical NHE.
- Subjects :
- Absorption (pharmacology)
Sodium-Hydrogen Exchangers
Physiology
Inorganic chemistry
Methazolamide
Salt (chemistry)
SLC26A3
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Transfection
Endocytosis
Clathrin
Antiporters
Amiloride
Mice
Chlorides
Mucosal Biology
Physiology (medical)
Intestine, Small
Cyclic AMP
Animals
Humans
Chloride-Bicarbonate Antiporters
RNA, Messenger
chemistry.chemical_classification
Hepatology
Ion exchange
biology
Sodium Radioisotopes
Sodium-Hydrogen Exchanger 3
Chemistry
Sodium
Gastroenterology
Niflumic Acid
Epithelial Cells
Coupling (electronics)
Protein Transport
Membrane
Sulfate Transporters
Synaptotagmin I
biology.protein
Biophysics
Calcium
Caco-2 Cells
Subjects
Details
- ISSN :
- 15221547 and 01931857
- Volume :
- 296
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Accession number :
- edsair.doi.dedup.....f26a86aa81d15da14f2a66d82b492684