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MUCOSAL BIOLOGY

Ileal oxalate absorption and urinary oxalate excretion are enhanced in Slc26a6 null mice

¹Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida ²Department of Medicine, University of Cincinnati, Cincinnati, Ohio

Submitted 11 October 2005 ; accepted in final form 13 December 2005

Intestinal oxalate transport, mediated by anion exchange proteins, is important to oxalate homeostasis and consequently to calcium oxalate stone diseases. To assess the contribution of the putative anion transporter (PAT)1 (Slc26a6) to transepithelial oxalate transport, we compared the unidirectional and net fluxes of oxalate across isolated, short-circuited segments of the distal ileum of wild-type (WT) mice and Slc26a6 null mice [knockout (KO)]. Additionally, urinary oxalate excretion was measured in both groups. In WT mouse ileum, there was a small net secretion of oxalate (), whereas in KO mice J_net^Ox was significantly absorptive (75 ± 10 pmol·cm^–2h·h^–1), which was the result of a smaller serosal-to-mucosal oxalate flux (J_sm^Ox) and a larger mucosal-to-serosal oxalate flux (J_ms^Ox). Mucosal DIDS (200 µM) reduced J_sm^Ox in WT mice, leading to reversal of the direction of net oxalate transport from secretion to absorption () , but DIDS had no significant effect on KO ileum. In WT mice in the absence of mucosal Cl^–, there were small increases in J_ms^Ox and decreases in J_sm^Ox that led to a small net oxalate absorption. In KO mice, J_net^Ox was 1.5-fold greater in the absence of mucosal Cl^–, due solely to an increase in J_ms^Ox. Urinary oxalate excretion was about fourfold greater in KO mice compared with WT littermates. We conclude that PAT1 is DIDS sensitive and mediates a significant fraction of oxalate efflux across the apical membrane in exchange for Cl^–; as such, PAT1 represents a major apical membrane pathway mediating J_sm^Ox.

putative anion transporter 1; hyperoxaluria; anion exchange; serum oxalate; 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid

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