The anion exchanger PAT-1 (Slc26a6) does not participate in oxalate or chloride transport by mouse large intestine

Jonathan M. Whittamore, Marguerite Hatch

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The membrane-bound transport proteins responsible for oxalate secretion across the large intestine remain unidentified. The apical chloride/bicarbonate (Cl/HCO3) exchanger encoded by Slc26a6, known as PAT-1 (putative anion transporter 1), is a potential candidate. In the small intestine, PAT-1 makes a major contribution to oxalate secretion but whether this role extends into the large intestine has not been directly tested. Using the PAT-1 knockout (KO) mouse, we compared the unidirectional absorptive (Jmsion) and secretory (Jsmion) flux of oxalate and Cl across cecum, proximal colon, and distal colon from wild-type (WT) and KO mice in vitro. We also utilized the non-specific inhibitor DIDS (4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid) to confirm a role for PAT-1 in WT large intestine and (in KO tissues) highlight any other apical anion exchangers involved. Under symmetrical, short-circuit conditions the cecum and proximal colon did not transport oxalate on a net basis, whereas the distal colon supported net secretion. We found no evidence for the participation of PAT-1, or indeed any other DIDS-sensitive transport mechanism, in oxalate or Cl by the large intestine. Most unexpectedly, mucosal DIDS concurrently stimulated JmsOx and JsmOx by 25–68% across each segment without impacting net transport. For the colon, these changes were directly proportional to increased transepithelial conductance suggesting this response was the result of bidirectional paracellular flux. In conclusion, PAT-1 does not contribute to oxalate or Cl transport by the large intestine, and we urge caution when using DIDS with mouse colonic epithelium.

Original languageEnglish (US)
Pages (from-to)95-106
Number of pages12
JournalPflugers Archiv European Journal of Physiology
Volume473
Issue number1
DOIs
StatePublished - Jan 2021
Externally publishedYes

Keywords

  • Dicarboxylic acid
  • Radiotracer
  • Solute carrier
  • Ussing chamber

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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