Transcellular oxalate and Cl- absorption in mouse intestine is mediated by the DRA anion exchanger Slc26a3, and DRA deletion decreases urinary oxalate

Am J Physiol Gastrointest Liver Physiol. 2013 Oct 1;305(7):G520-7. doi: 10.1152/ajpgi.00167.2013. Epub 2013 Jul 25.


Active transcellular oxalate transport in the mammalian intestine contributes to the homeostasis of this important lithogenic anion. Several members of the Slc26a gene family of anion exchangers have a measurable oxalate affinity and are expressed along the gut, apically and basolaterally. Mouse Slc26a6 (PAT1) targets to the apical membrane of enterocytes in the small intestine, and its deletion results in net oxalate absorption and hyperoxaluria. Apical exchangers of the Slc26a family that mediate oxalate absorption have not been established, yet the Slc26a3 [downregulated in adenoma (DRA)] protein is a candidate mediator of oxalate uptake. We evaluated the role of DRA in intestinal oxalate and Cl(-) transport by comparing unidirectional and net ion fluxes across short-circuited segments of small (ileum) and large (cecum and distal colon) intestine from wild-type (WT) and DRA knockout (KO) mice. In WT mice, all segments demonstrated net oxalate and Cl(-) absorption to varying degrees. In KO mice, however, all segments exhibited net anion secretion, which was consistently, and solely, due to a significant reduction in the absorptive unidirectional fluxes. In KO mice, daily urinary oxalate excretion was reduced 66% compared with that in WT mice, while urinary creatinine excretion was unchanged. We conclude that DRA mediates a predominance of the apical uptake of oxalate and Cl(-) absorbed in the small and large intestine of mice under short-circuit conditions. The large reductions in urinary oxalate excretion underscore the importance of transcellular intestinal oxalate absorption, in general, and, more specifically, the importance of the DRA exchanger in oxalate homeostasis.

Keywords: anion exchange; chloride-losing diarrhea; hyperoxaluria; kidney stones; large intestine; nephrolithiasis; small intestine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorption
  • Animals
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Biological Transport / physiology
  • Cecum / metabolism
  • Chlorides / metabolism*
  • Electrophysiological Phenomena
  • Gene Expression Regulation / physiology
  • Homeostasis
  • Ileum / metabolism
  • Mice
  • Mice, Knockout
  • Oxalates / metabolism*
  • Sulfate Transporters


  • Antiporters
  • Chlorides
  • Oxalates
  • Slc26a3 protein, mouse
  • Slc26a6 protein, mouse
  • Sulfate Transporters