The anion exchanger PAT-1 (Slc26a6) does not participate in oxalate or chloride transport by mouse large intestine
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ION CHANNELS, RECEPTORS AND TRANSPORTERS
The anion exchanger PAT-1 (Slc26a6) does not participate in oxalate or chloride transport by mouse large intestine Jonathan M. Whittamore 1
&
Marguerite Hatch 1
Received: 9 August 2020 / Revised: 23 October 2020 / Accepted: 10 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 − ion absorptive (J ion ms ) and secretory (J sm ) 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 Ox mechanism, in oxalate or Cl− by the large intestine. Most unexpectedly, mucosal DIDS concurrently stimulated J Ox ms and J sm 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. Keywords Ussing chamber . Radiotracer . Dicarboxylic acid . Solute carrier
Introduction Oxalate is part of the diet and a non-functional end-product of metabolism. It is normally cleared without complication by the kidneys, although elevated oxalate in the urine (hyperoxaluria) is a risk factor for the formation of insoluble calcium oxalate, a primary constituent of the vast majority of kidney stones [6, 21, 64]. The gastrointestinal (GI) tract also has a vital role where absorption of ingested oxalate makes an important contribution to its appearance in the urine [12, 44, 90]. Additionally, the intestine is also a valuable extra-renal pathway for oxalate elimination, displaying a substantial
* Jonathan M. Whittamore [email protected] 1
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, PO Box 100275, 1600 SW Archer Rd, Gainesville, FL 32610, USA
adaptive capacity for secretion of this waste metabolite, capable of reducing urinary output [33, 34]. Identifying and cha
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