Sodium and chloride absorptive defects in the small intestine in Slc26a6 null mice

Abstract

PAT1 (Slc26a6) is located on the apical membrane of the small intestinal villi, but its role for salt absorption has not been studied. To ascertain the role of Slc26a6 in jejunal sodium and chloride absorption, and its interplay with NHE3, muscle-stripped jejuna from Slc26a6+/+ and -/- and NHE3 +/+ and -/- mice were mounted in Ussing chambers and electrical parameters, and (36)Cl(-) and (22)Na(+) fluxes were measured. In parallel studies, expression of the apical Na(+)/H(+) exchanger (NHE3) was examined by immunofluorescence labeling and immunoblot analysis in brush border membrane (BBM). In the basal state, net Cl(-) and Na(+) fluxes were absorptive in Slc26a6-/- and +/+ jejuni, but significantly decreased in -/- animals. Upon forskolin addition, net Na(+) absorption decreased, Isc strongly increased, and net Cl(-) flux became secretory in Slc26a6-/- and +/+ jejuni. When luminal glucose was added to activate Na(+)/glucose cotransport, concomitant Cl(-) absorption was significantly reduced in Slc26a6 -/- jejuni, while Na(+) absorption increased to the same degree in Slc26a6 -/- and +/+ jejuni. Identical experiments in NHE3-deficient jejuni also showed reduced Na(+) and Cl(-) absorption. Results further demonstrated that the lack of NHE3 rendered Na(+) and Cl(-) absorption unresponsive to inhibition by cAMP, but did not affect glucose-driven Na(+) and Cl(-) absorption. Immunoblotting revealed comparable NHE3 abundance and distribution in apical membranes in Slc26a6-/- and +/+ mice. The data strongly suggests that Slc26a6 acts in concert with NHE3 in electroneutral salt absorption in the small intestine. Slc26a6 also serves to absorb Cl(-) during glucose-driven salt absorption.

Characterization of CFTR High Expresser cells in the intestine

“…and NHE3 interact (42), supporting the observed defects in Na ϩ and Cl Ϫ absorption in the small intestine of SLC26A6-null mice (45).…”

Leptin regulates sugar and amino acids transport in the human intestinal cell line Caco‐2

“…As previously mentioned, activity of the apical Na + /H + exchanger maintains the H + electrochemical gradient necessary for the correct functionality of PAT1 (Anderson et al 2004, Seidler et al 2008. Moreover, it has been demonstrated that activation of cAMP/PKA pathway decreases the activity of the Na + /H + exchanger NHE3 (Anderson & Thwaites 2005) and indirectly inhibits PAT1, in line with the fact that PAT1 has no intracellular PKA phosphorylation sites (Chen et al 2004).…”

The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport

“…Slc26a6 -/-mice show impaired intestinal and pancreatic duct Clabsorption and HCO 3 -secretion (42,99,123), along with impaired pancreatic fluid secretion (123). Moreover, deletion of Slc26a6 in the pancreatic duct results in disregulation of CFTR (123), indicating a role of Slc26a6 in the overall epithelial fluid and electrolyte secretion.…”