title: Sat1 is dispensable for active oxalate secretion in mouse duodenum.
abstract: Mice deficient for the apical membrane oxalate transporter SLC26A6 develop hyperoxalemia, hyperoxaluria, and calcium oxalate stones due to a defect in intestinal oxalate secretion. However, the nature of the basolateral membrane oxalate transport process that operates in series with SLC26A6 to mediate active oxalate secretion in the intestine remains unknown. Sulfate anion transporter-1 (Sat1 or SLC26A1) is a basolateral membrane anion exchanger that mediates intestinal oxalate transport. Moreover, Sat1-deficient mice also have a phenotype of hyperoxalemia, hyperoxaluria, and calcium oxalate stones. We, therefore, tested the role of Sat1 in mouse duodenum, a tissue with Sat1 expression and SLC26A6-dependent oxalate secretion. Although the active secretory flux of oxalate across mouse duodenum was strongly inhibited (>90%) by addition of the disulfonic stilbene DIDS to the basolateral solution, secretion was unaffected by changes in medium concentrations of sulfate and bicarbonate, key substrates for Sat1-mediated anion exchange. Inhibition of intracellular bicarbonate production by acetazolamide and complete removal of bicarbonate from the buffer also produced no change in oxalate secretion. Finally, active oxalate secretion was not reduced in Sat1-null mice. We conclude that a DIDS-sensitive basolateral transporter is involved in mediating oxalate secretion across mouse duodenum, but Sat1 itself is dispensable for this process.
authors.affiliation: Section of Nephrology, Dept. of Internal Medicine, Yale School of Medicine, New Haven, CT 06520-8029, USA.
authors.forename: Narae
authors.initials: N
authors.lastname: Ko
authors.forename: Felix
authors.initials: F
authors.lastname: Knauf
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Daniel
authors.initials: D
authors.lastname: Markovich
authors.forename: Peter S
authors.initials: PS
authors.lastname: Aronson
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D027321:Anion Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017920:Antiporters / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001693:Biological Transport, Active; D004386:Duodenum / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010070:Oxalates / Q000378:metabolism*; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D010070:Oxalates; C466903:Slc26a1 protein, mouse; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; D000086:Acetazolamide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid