Date of Award
Medical Doctor (MD)
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 mechanism of intestinal oxalate absorption and the basolateral membrane oxalate transport process that operates in series with SLC26A6 to mediate active oxalate secretion in the intestine remain unresolved. To investigate the nature of intestinal absorption in mice duodenum, we tested the affect of lumen-negative transepithelial potential difference and cation complex formation on oxalate absorption. Oxalate absorptive flux increased with lumen-negative transepithelial potential difference but was unaffected by an increased fraction of cation-bound oxalate. The results are consistent with previously proposed cell model that intestinal oxalate absorption takes place via paracellular pathway rather than mediated, transcellular pathway.
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 an increased fraction of cation-bound oxalate and 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.
Ko, Narae, "Epithelial Transport Of Oxalate In Mouse Duodenum" (2012). Yale Medicine Thesis Digital Library. 1736.