Chloride and bicarbonate have similar affinities to the intestinal anion exchanger DRA (down regulated in adenoma)

DRA (down regulated in adenoma, SLC26A3) is an anion exchanger that mediates electroneutral NaCl absorption in the ileum and proximal colon together with NHE3 (Na/H exchanger isoform 3), and that is involved in duodenal and possibly pancreatic bicarbonate secretion. Thus, its chloride and bicarbonate affinities are important for both processes. [Cl]_i and pH_i transients were measured using MQAE and BCECF. HEK293 cells stably expressing DRA were exposed to 0 mM Cl at various [HCO₃] (9 to 51 mM, at 5% CO₂ or 15 to 57 mM, at pH 7.5) to determine the HCO₃ affinity. After intracellular Cl depletion, 10, 30, and 90 mM Cl were readded at various [HCO₃]s to determine the relative Cl and HCO₃ affinities. The k _0.5 for extracellular HCO₃ is between 18.5 and 32.8 mM. Cl and HCO₃ compete with similar affinities for transport by DRA. DRA activity is independent of pH_o between 7.0 and 7.75. DRA is activated by alkaline pH_i. Competition of Cl and HCO₃ does not significantly impair NaCl absorption, because in the ileum and colon, luminal Cl is comparably high. Activation at alkaline pH_i supports functional coupling of DRA and NHE3 by the subapical pH_i. In the distal pancreatic ductal system, luminal HCO₃ is high compared to luminal Cl. Under these conditions, competition of Cl and HCO₃ is difficult to reconcile with a role of DRA in Cl reabsorption in exchange for HCO₃. Our data, thus, provide indirect evidence against a role of DRA in pancreatic HCO₃ secretion.