Pendrin as a Novel Target for Diuretic Therapy
Open Access
- 1 January 2011
- journal article
- review article
- Published by S. Karger AG in Cellular Physiology and Biochemistry
- Vol. 28 (3), 521-526
- https://doi.org/10.1159/000335117
Abstract
The Cl(-)/HCO(3)(-) exchanger pendrin (SLC26A4, PDS) and the thiazide-sensitive NaCl cotransporter NCC (SLC12A3) are expressed on the apical membranes of distal nephron segments and mediate salt absorption, with pendrin working in tandem with the epithelial Na channel (ENaC) and NCC working by itself. Pendrin is expressed on the apical membrane of intercalated cells in late distal convoluted tubule (DCT), connecting tubule (CNT) and the cortical collecting duct (CCD) whereas the thiazide-sensitive NaCl cotransporter NCC is primarily detected on the apical membrane of DCT cells. Recent studies indicate that pendrin expression is increased in kidneys of NCC knockout mice, raising the possibility that pendrin and NCC can compensate for loss of the other by increasing their expression and activity. Current investigations in our laboratories demonstrate that pendrin plays an important role in compensatory salt absorption in response to the loop diuretics and the thiazide derivatives. These studies further demonstrate that whereas single deletion of pendrin or NCC does not cause salt wasting in mutant mice under baseline conditions, double knockout of pendrin and NCC causes profound polyuria and polydipsia, along with salt wasting under basal conditions. As a result, animals develop significant dehydration. We propose that pharmacologic inhibition of pendrin and NCC can provide a novel and strong diuretic regimen for patients with fluid overload, including those with congestive heart failure, nephrotic syndrome or renal failure.Keywords
This publication has 35 references indexed in Scilit:
- Nedd4-2 Modulates Renal Na+-Cl− Cotransporter via the Aldosterone-SGK1-Nedd4-2 PathwayJournal of the American Society of Nephrology, 2011
- Thiazide and Loop DiureticsThe Journal of Clinical Hypertension, 2011
- Inhibition of K+ secretion in the distal nephron in nephrotic syndrome: possible role of albuminuriaThe Journal of Physiology, 2011
- Deletion of the anion exchanger Slc26a4 (pendrin) decreases apical Cl−/HCO3−exchanger activity and impairs bicarbonate secretion in kidney collecting ductAmerican Journal of Physiology-Cell Physiology, 2010
- Aldosterone and vasopressin affect - and -ENaC mRNA translationNucleic Acids Research, 2010
- The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of miceJCI Insight, 2010
- Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathwayJCI Insight, 2009
- REGULATION OF EPITHELIAL Na+CHANNELS BY ALDOSTERONE: ROLE OF Sgk1Clinical and Experimental Pharmacology and Physiology, 2008
- The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complexJCI Insight, 2007
- Properties of the basolateral membrane of the cortical thick ascending limb of Henle's loop of rabbit kidneyPflügers Archiv - European Journal of Physiology, 1983