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Abstract
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]^sub i^ and pH^sub i^ transients were measured using MQAE and BCECF. HEK293 cells stably expressing DRA were exposed to 0 mM Cl at various [HCO^sub 3^] (9 to 51 mM, at 5% CO^sub 2^ or 15 to 57 mM, at pH 7.5) to determine the HCO^sub 3^ affinity. After intracellular Cl depletion, 10, 30, and 90 mM Cl were readded at various [HCO^sub 3^]s to determine the relative Cl and HCO^sub 3^ affinities. The k ^sub 0.5^ for extracellular HCO^sub 3^ is between 18.5 and 32.8 mM. Cl and HCO^sub 3^ compete with similar affinities for transport by DRA. DRA activity is independent of pH^sub o^ between 7.0 and 7.75. DRA is activated by alkaline pH^sub i^. Competition of Cl and HCO^sub 3^ does not significantly impair NaCl absorption, because in the ileum and colon, luminal Cl is comparably high. Activation at alkaline pH^sub i^ supports functional coupling of DRA and NHE3 by the subapical pH^sub i^. In the distal pancreatic ductal system, luminal HCO^sub 3^ is high compared to luminal Cl. Under these conditions, competition of Cl and HCO^sub 3^ is difficult to reconcile with a role of DRA in Cl reabsorption in exchange for HCO^sub 3^. Our data, thus, provide indirect evidence against a role of DRA in pancreatic HCO^sub 3^ secretion.[PUBLICATION ABSTRACT]