Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion.
Mice lacking the oxalate transporter SLC26A6 develop hyperoxalemia, hyperoxaluria, and calcium-oxalate stones as a result of a defect in intestinal oxalate secretion, but what accounts for the absorptive oxalate flux remains unknown. We measured transepithelial absorption of [(14)C]oxalate simultaneously with the flux of [(3)H]mannitol, a marker of the paracellular pathway, across intestine from wild-type and Slc26a6-null mice. We used the anion transport inhibitor DIDS to investigate other members of the SLC26 family that may mediate transcellular oxalate absorption. Absorptive flux of oxalate in duodenum was similar to mannitol, insensitive to DIDS, and nonsaturable, indicating that it is predominantly passive and paracellular. In contrast, in wild-type mice, secretory flux of oxalate in duodenum exceeded that of mannitol, was sensitive to DIDS, and saturable, indicating transcellular secretion of oxalate. In Slc26a6-null mice, secretory flux of oxalate was similar to mannitol, and no net flux of oxalate occurred. Absorptive fluxes of both oxalate and mannitol varied in parallel in different segments of small and large intestine. In epithelial cell lines, modulation of the charge selectivity of the claudin-based pore pathway did not affect oxalate permeability, but knockdown of the tight-junction protein ZO-1 enhanced permeability to oxalate and mannitol in parallel. Moreover, formation of soluble complexes with cations did not affect oxalate absorption. In conclusion, absorptive oxalate flux occurs through the paracellular "leak" pathway, and net absorption of dietary oxalate depends on the relative balance between absorption and SLC26A6-dependent transcellular secretion.
Section of Nephrology., Department of Internal Medicine, Yale University School of Medicine, P.O. Box 208029, One Gilbert Street, TAC S-255, New Haven, Connecticut 06520-8029, USA.
Felix
F
Knauf
Narae
N
Ko
Zhirong
Z
Jiang
William G
WG
Robertson
Christina M
CM
Van Itallie
James M
JM
Anderson
Peter S
PS
Aronson
D000818:Animals; D017920:Antiporters / Q000502:physiology*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D010070:Oxalates / Q000378:metabolism*; D000076988:Sulfate Transporters
D017920:Antiporters; D010070:Oxalates; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters