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

Abstract

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 ([Formula: see text]), whereas in KO mice JnetOxwas significantly absorptive (75 ± 10 pmol·cm−2h·h−1), which was the result of a smaller serosal-to-mucosal oxalate flux ( JsmOx) and a larger mucosal-to-serosal oxalate flux ( JmsOx). Mucosal DIDS (200 μM) reduced JsmOxin WT mice, leading to reversal of the direction of net oxalate transport from secretion to absorption ([Formula: see text]) , but DIDS had no significant effect on KO ileum. In WT mice in the absence of mucosal Cl−, there were small increases in JmsOxand decreases in JsmOxthat led to a small net oxalate absorption. In KO mice, JnetOxwas 1.5-fold greater in the absence of mucosal Cl−, due solely to an increase in JmsOx. 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 JsmOx.