TY - JOUR
T1 - Deletion of the chloride transporter Slc26a7 causes distal renal tubular acidosis and impairs gastric acid secretion
AU - Xu, Jie
AU - Song, Penghong
AU - Nakamura, Suguru
AU - Miller, Marian
AU - Barone, Sharon
AU - Alper, Seth L.
AU - Riederer, Brigitte
AU - Bonhagen, Janina
AU - Arend, Lois J.
AU - Amlal, Hassane
AU - Seidler, Ursula
AU - Soleimani, Manoocher
PY - 2009/10/23
Y1 - 2009/10/23
N2 - SLC26A7 (human)/Slc26a7 (mouse) is a recently identified chloride-base exchanger and/or chloride transporter that is expressed on the basolateral membrane of acid-secreting cells in the renal outer medullary collecting duct (OMCD) and in gastric parietal cells. Here, we show that mice with genetic deletion of Slc26a7 expression develop distal renal tubular acidosis, as manifested by metabolic acidosis and alkaline urine pH. In the kidney, basolateral Cl-/HCO3- exchange activity in acid-secreting intercalated cells in the OMCD was significantly decreased in hypertonic medium (a normal milieu for the medulla) but was reduced only mildly in isotonic medium. Changing from a hypertonic to isotonic medium (relative hypotonicity) decreased the membrane abundance of Slc26a7 in kidney cells in vivo and in vitro. In the stomach, stimulated acid secretion was significantly impaired in isolated gastric mucosa and in the intact organ. We propose that SLC26A7 dysfunction should be investigated as a potential cause of unexplained distal renal tubular acidosis or decreased gastric acid secretion in humans.
AB - SLC26A7 (human)/Slc26a7 (mouse) is a recently identified chloride-base exchanger and/or chloride transporter that is expressed on the basolateral membrane of acid-secreting cells in the renal outer medullary collecting duct (OMCD) and in gastric parietal cells. Here, we show that mice with genetic deletion of Slc26a7 expression develop distal renal tubular acidosis, as manifested by metabolic acidosis and alkaline urine pH. In the kidney, basolateral Cl-/HCO3- exchange activity in acid-secreting intercalated cells in the OMCD was significantly decreased in hypertonic medium (a normal milieu for the medulla) but was reduced only mildly in isotonic medium. Changing from a hypertonic to isotonic medium (relative hypotonicity) decreased the membrane abundance of Slc26a7 in kidney cells in vivo and in vitro. In the stomach, stimulated acid secretion was significantly impaired in isolated gastric mucosa and in the intact organ. We propose that SLC26A7 dysfunction should be investigated as a potential cause of unexplained distal renal tubular acidosis or decreased gastric acid secretion in humans.
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U2 - 10.1074/jbc.M109.044396
DO - 10.1074/jbc.M109.044396
M3 - Article
C2 - 19723628
AN - SCOPUS:70350366746
SN - 0021-9258
VL - 284
SP - 29470
EP - 29479
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 43
ER -