ArticleGastroenterology2008
Down-regulated in adenoma Cl/HCO3 exchanger couples with Na/H exchanger 3 for NaCl absorption in murine small intestine.
Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 98 citations in OpenAlex.
- n-3 Polyunsaturated Fatty Acids Improve DSS-Induced Acute Colitis in Mice via Intestinal Barrier Fortification and Gut Microbiome Modulation.Digestive diseases and sciences · 2026Article
- Lactylation of SLC26A3 in the acidic tumor microenvironment promotes malignant progression of colorectal carcinoma.Cell death & disease · 2026Article
- Mechanism of reduced intestinal phosphate absorption by tenapanor: a hypothesis.Clinical kidney journal · 2026Review
- Wuji Wan ameliorates ulcerative colitis by restoring impaired membrane transport.Frontiers in pharmacology · 2026Article
- Roles and therapeutic potential of the SLC family in prostate cancer-literature review.BMC urology · 2025Review
- Intestinal Epithelial Cell Brush Border Membrane Cl:HCOInternational journal of molecular sciences · 2024Article
- Review
- SLC26 Anion Transporters.Handbook of experimental pharmacology · 2024Review
- A Novel Peptide Prevents Enterotoxin- and Inflammation-Induced Intestinal Fluid Secretion by Stimulating Sodium-Hydrogen Exchanger 3 Activity.Gastroenterology · 2023Article
- SLC26A3 (DRA) is stimulated in a synergistic, intracellular CaAmerican journal of physiology. Cell physiology · 2023Article
- Small molecule inhibitors of intestinal epithelial anion exchanger SLC26A3 (DRA) with a luminal, extracellular site of action.European journal of medicinal chemistry · 2023Article
- Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt.International journal of molecular sciences · 2023Review
- Oxalate secretion is stimulated by a cAMP-dependent pathway in the mouse cecum.Pflugers Archiv : European journal of physiology · 2023Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- SLC26A6-selective inhibitor identified in a small-molecule screen blocks fluid absorption in small intestine.JCI insight · 2021Article
- The role of NHE3 (Slc9a3) in oxalate and sodium transport by mouse intestine and regulation by cAMP.Physiological reports · 2021Article
- Article
- The anion exchanger PAT-1 (Slc26a6) does not participate in oxalate or chloride transport by mouse large intestine.Pflugers Archiv : European journal of physiology · 2021Article
- Ion Transport Basis of Diarrhea in a Mouse Model of Adoptive T Cell Transfer Colitis.Digestive diseases and sciences · 2020Article
- Physiological and Pathological Functions of SLC26A6.Frontiers in medicine · 2020Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsElectroneutral NaCl absorption across small intestine contributes importantly to systemic fluid balance. Disturbances in this process occur in both obstructive and diarrheal diseases, eg, cystic fibrosis, secretory diarrhea. NaCl absorption involves coupling of Cl(-)/HCO(3)(-) exchanger(s) primarily with Na(+)/H(+) exchanger 3 (Nhe3) at the apical membrane of intestinal epithelia. Identity of the coupling Cl(-)/HCO(3)(-) exchanger(s) was investigated using mice with gene-targeted knockout (KO) of Cl(-)/HCO(3)(-) exchangers: Slc26a3, down-regulated in adenoma (Dra) or Slc26a6, putative anion transporter-1 (Pat-1).
methodsIntracellular pH (pH(i)) of intact jejunal villous epithelium was measured by ratiometric microfluoroscopy. Ussing chambers were used to measure transepithelial (22)Na(36)Cl flux across murine jejunum, a site of electroneutral NaCl absorption. Expression was estimated using immunofluorescence and quantitative polymerase chain reaction.
resultsBasal pH(i) of DraKO epithelium, but not Pat-1KO epithelium, was alkaline, whereas pH(i) in the Nhe3KO was acidic relative to wild-type. Altered pH(i) was associated with robust Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange activity in the DraKO and Nhe3KO villous epithelium, respectively. Contrary to genetic ablation, pharmacologic inhibition of Nhe3 in wild-type did not alter pH(i) but coordinately inhibited Dra. Flux studies revealed that Cl(-) absorption was essentially abolished (>80%) in the DraKO and little changed (<20%) in the Pat-1KO jejunum. Net Na(+) absorption was unaffected. Immunofluorescence demonstrated modest Dra expression in the jejunum relative to large intestine. Functional and expression studies did not indicate compensatory changes in relevant transporters.
conclusionsThese studies provide functional evidence that Dra is the major Cl(-)/HCO(3)(-) exchanger coupled with Nhe3 for electroneutral NaCl absorption across mammalian small intestine.
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