Xu Jie, Song Penghong, Nakamura Suguru, Miller Marian, Barone Sharon, Alper Seth L, Riederer Brigitte, Bonhagen Janina, Arend Lois J, Amlal Hassane, Seidler Ursula, Soleimani Manoocher
Research Services, Veterans Affairs Medical Center, Cincinnati, Ohio 45220, USA.
J Biol Chem. 2009 Oct 23;284(43):29470-9. doi: 10.1074/jbc.M109.044396. Epub 2009 Sep 1.
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.
SLC26A7（人类）/Slc26a7（小鼠）是一种最近被鉴定出的氯碱交换体和/或氯转运体，在肾外髓集合管（OMCD）的泌酸细胞以及胃壁细胞的基底外侧膜上表达。在此，我们表明，Slc26a7基因缺失表达的小鼠会发生远端肾小管酸中毒，表现为代谢性酸中毒和尿液pH呈碱性。在肾脏中，OMCD中泌酸闰细胞的基底外侧Cl(-)/HCO3(-)交换活性在高渗介质（髓质的正常环境）中显著降低，但在等渗介质中仅轻度降低。从高渗介质转变为等渗介质（相对低渗）会降低体内和体外肾脏细胞中Slc26a7的膜丰度。在胃中，分离的胃黏膜和完整器官中刺激后的胃酸分泌均显著受损。我们建议，应将SLC26A7功能障碍作为人类不明原因远端肾小管酸中毒或胃酸分泌减少的潜在原因进行研究。
