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The apical membrane Cl/oxalate exchanger SLC26A6 has been demonstrated to play a role in proximal tubule NaCl transport based on studies in microperfused tubules. The present study is directed at characterizing the role of SLC26A6 in NaCl homeostasis in vivo under physiological conditions. Free-flow micropuncture studies revealed that volume and Cl absorption were similar in surface proximal tubules of wild-type and Slc26a6 mice. Moreover, the increments in urine flow rate and sodium excretion following thiazide and furosemide infusion were identical in wild-type and Slc26a6 mice, indicating no difference in NaCl delivery out of the proximal tubule. The absence of an effect of deletion of SLC26A6 on NaCl homeostasis was further supported by the absence of lower blood pressure in Slc26a6 compared with wild-type mice on normal or low-salt diets. Moreover, raising plasma and urine oxalate by feeding mice a diet enriched in soluble oxalate did not affect mean blood pressure. In contrast to the lack of effect of SLC26A6 deletion on NaCl homeostasis, fractional excretion of oxalate was reduced from 1.6 in wild-type mice to 0.7 in Slc26a6 mice. We conclude that, although SLC26A6 is dispensable for renal NaCl homeostasis, it is required for net renal secretion of oxalate.
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http://dx.doi.org/10.1152/ajprenal.00309.2018 | DOI Listing |
Front Pharmacol
January 2025
Department of Gastroenterology, Hannover Medical School, Hanover, Germany.
SLC26A6, a member of the SLC26 family of multifunctional anion transporters, has been particularly enigmatic because of its multiple modes of transport, its expression in organs that are difficult to study physiologically, and the lack of specific antibodies and inhibitors. This has recently changed. SLC26A6 is expressed in the human pancreas, kidney, intestine, heart and some other organs and is involved in fluid absorption, anion secretion, regulation of intracellular pH and elimination of waste products such as oxalate.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA. Electronic address:
Pendrin (SLC26A4) is an anion exchanger expressed in epithelial cells of kidney and lung. Pendrin inhibition is a potential treatment approach for edema, hypertension and inflammatory lung diseases. We have previously identified first-in-class pendrin inhibitors by high-throughput screening, albeit with low potency for pendrin inhibition (IC ∼10 μM).
View Article and Find Full Text PDFGastroenterology
September 2024
Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois. Electronic address:
Background & Aims: Putative anion transporter-1 (PAT1, SLC26A6) plays a key role in intestinal oxalate and bicarbonate secretion. PAT1 knockout (PKO) mice exhibit hyperoxaluria and nephrolithiasis. Notably, diseases such as inflammatory bowel disease are also associated with higher risk of hyperoxaluria and nephrolithiasis.
View Article and Find Full Text PDFPflugers Arch
April 2024
Department of Gastroenterology, Hannover Medical School, 30625, Hannover, Germany.
The transport of bicarbonate across the enterocyte cell membrane regulates the intracellular as well as the luminal pH and is an essential part of directional fluid movement in the gut. Since the first description of "active" transport of HCO ions against a concentration gradient in the 1970s, the fundamental role of HCO transport for multiple intestinal functions has been recognized. The ion transport proteins have been identified and molecularly characterized, and knockout mouse models have given insight into their individual role in a variety of functions.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
May 2024
Department of Mathematics, University of Auckland, Auckland, New Zealand.
Cystic fibrosis (CF) is a genetic disease caused by the mutations of cystic fibrosis transmembrane conductance regulator (), the cystic fibrosis transmembrane conductance regulator gene. Cftr is a critical ion channel expressed in the apical membrane of mouse salivary gland striated duct cells. Although Cftr is primarily a Cl channel, its knockout leads to higher salivary Cl and Na concentrations and lower pH.
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