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1 Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
2 Department of Pathology, University of Cincinnati, Cincinnati, OH, USA
* To whom correspondence should be addressed. E-mail: rfreel{at}ufl.edu.
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 PAT1 (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 (KO). Additionally, urinary oxalate excretion was measured in both groups. In WT mouse ileum there was a small net secretion of oxalate (JnetOx = - 5.0 ± 5.0 pmole/cm-2/h-1) whereas in KO mice JnetOx was significantly absorptive (75 ± 10 pmole/cm-2/h-1) which was due to a smaller serosal to mucosal oxalate flux (JsmOx) and a larger mucosal to serosal oxalate flux (JmsOx). Mucosal DIDS (200 µM) reduced JsmOx in WT mice leading to reversal of the direction of net oxalate transport from secretion to absorption (JnetOx = 15.0 ± 5.0 pmole/cm-2/h-1), but DIDS had no significant effect on KO ileum. In WT mice in the absence of mucosal chloride, there were small increases in JmsOx and decreases in JsmOx which led to a small net oxalate absorption. In KO mice JnetOx was 1.5 fold greater in the absence of mucosal chloride, due solely to an increase in JmsOx. Urinary oxalate excretion was about 4 fold greater in KO mice compared to WT littermates. We conclude that PAT1 is DIDS-sensitive and mediates a significant fraction of oxalate efflux across the apical membrane in exchange for chloride; as such PAT1 represents a major apical membrane pathway mediating JsmOx.
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