Adaptation to metabolic acidosis and its recovery are associated with changes in anion exchanger distribution and expression in the cortical collecting duct

Purkerson, Jeffrey M.; Tsuruoka, Shuichi; Suter, DE; Nakamori, Aya; Schwartz, George J.

doi:10.1038/ki.2010.195

Cited by 42 publications

(49 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is now evidence that type A and type B intercalated cell types represent different states of differentiation, as proposed by Al-Awqati and confirmed by others (16). In some of these studies carried out in the rabbit model, adaptation to acidosis was not accompanied by changes in the number of intercalated cells but rather by a change from type B to type A intercalated cells (7,43). The transition process from type B to type A intercalated cell depends on the basolateral deposition of the extracellular matrix proteins hensin (DMBT1), galectin 3, and other proteins (7,44).…”

Section: Intercalated Cell Distribution Nomenclature Morphology Anmentioning

confidence: 57%

Collecting Duct Intercalated Cell Function and Regulation

Roy¹,

Al‐bataineh²,

Pastor-Soler

2015

Clinical Journal of the American Society of Nephrology

202

213

View full text Add to dashboard Cite

Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla. Intercalated cells are interspersed among the more numerous segment-specific principal cells. There are three types of intercalated cells, each having distinct structures and expressing different ensembles of transport proteins that translate into very different functions in the processing of the urine. This review includes recent findings on how intercalated cells regulate their intracellular milieu and contribute to acid-base regulation and sodium, chloride, and potassium homeostasis, thus highlighting their potential role as targets for the treatment of hypertension. Their novel regulation by paracrine signals in the collecting duct is also discussed. Finally, this article addresses their role as part of the innate immune system of the kidney tubule.

show abstract

Section: Intercalated Cell Distribution Nomenclature Morphology Anmentioning

confidence: 57%

Collecting Duct Intercalated Cell Function and Regulation

Roy¹,

Al‐bataineh²,

Pastor-Soler

2015

Clinical Journal of the American Society of Nephrology

202

213

View full text Add to dashboard Cite

show abstract

“…Female New Zealand White rabbits weighing 1.5-3.0 kg were maintained on standard rabbit chow and tap water (21). Acid loading was accomplished by providing 100 mM NH4Cl-7.5% sucrose solution for 3 days with food intake limited to 30 g rabbit chow/day.…”

Section: Animalsmentioning

confidence: 99%

“…cDNA was synthesized from 0.5-2 g total RNA using the SuperScript first-strand synthesis system for RT-PCR, the Superscript III reverse transcriptase enzyme (Invitrogen, Carlsbad, CA), and random primers according to the manufacturer's recommended protocol. Specific primer sets and fluorogenic probes (TaqMan, fluorogenic 5=-nuclease chemistry) for rabbit pendrin and B1-VATPase were as previously described (21). The primer-probe set (forward primer: 5=-TGCCTTCTGCAGAGATTACAGCCT-3=, reverse primer: 5=-ATGAGGGCACAGAAACCTTCCTCA-3=, and probe: 5=-TGCTGGTGCGTTACTTCACCCGCTT-3=) specific for rabbit SLC4A9 (Accession No.…”

Section: Animalsmentioning

confidence: 99%

“…However, other studies have shown that pendrin expression is also dependent on urinary Cl Ϫ excretion (11,34) and, if unregulated, could cause hypertension (34). A study (21) of pendrin expression during acid-base disturbances revealed that the expression, mRNA, protein abundance, and number of pendrin-positive cells in rabbit kidneys were decreased after 3 days of acidosis. Similar findings have been observed in acidotic rats (20).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Insights into acidosis-induced regulation of SLC26A4 (pendrin) and SLC4A9 (AE4) transporters using three-dimensional morphometric analysis of β-intercalated cells

Purkerson

Heintz

Nakamori

et al. 2014

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

Purkerson JM, Heintz EV, Nakamori A, Schwartz GJ. Insights into acidosis-induced regulation of SLC26A4 (pendrin) and SLC4A9 (AE4) transporters using three-dimensional morphometric analysis of ␤-intercalated cells. Am J Physiol Renal Physiol 307: F601-F611, 2014. First published July 2, 2014; doi:10.1152/ajprenal.00404.2013.-The purpose of this study was to examine the three-dimensional (3-D) expression and distribution of anion transporters pendrin (SLC26A4) and anion exchanger (AE)4 (SLC4A9) in ␤-intercalated cells (␤-ICs) of the rabbit cortical collecting duct (CCD) to better characterize the adaptation to acid-base disturbances. Confocal analysis and 3-D reconstruction of ␤-ICs, using identifiers of the nucleus and zona occludens, permitted the specific orientation of cells from normal, acidotic, and recovering rabbits, so that adaptive changes could be quantified and compared. The pendrin cap likely mediates apical Cl Ϫ /HCO 3 Ϫ exchange, but it was also found beneath the zona occludens and in early endosomes, some of which may recycle back to the apical membrane via Rab11a ϩ vesicles. Acidosis reduced the size of the pendrin cap, observed as a large decrease in cap volume above and below the zona occludens, and the volume of the Rab11a ϩ apical recycling compartment. Correction of the acidosis over 12-18 h reversed these changes. Consistent with its proposed function in the basolateral exit of Na ϩ via Na ϩ -HCO 3 Ϫ cotransport, AE4 was expressed as a barrel-like structure in the lateral membrane of ␤-ICs. Acidosis reduced AE4 expression in ␤-ICs, but this was rapidly reversed during the recovery from acidosis. The coordinate regulation of pendrin and AE4 during acidosis and recovery is likely to affect the magnitude of acid-base and possibly Na ϩ transport across the CCD. In conclusion, acidosis induces a downregulation of AE expression in ␤-ICs and a diminished presence of pendrin in apical recycling endosomes. acidosis; alkalosis; anion exchangers; anion exchanger 4; confocal microscopy; rabbit FINAL REGULATION of acid-base transport occurs in the distal nephron of the kidney, particularly in the cortical collecting duct (CCD). We have previously shown in rabbits that acidosis results in increased proton secretion and decreased HCO 3 Ϫ secretion, respectively, by ␣-and ␤-intercalated cells (ICs) from isolated perfused CCDs (23,25,26,29). Some of these adaptive changes occur via a downregulation of the apical Cl Ϫ /HCO 3 Ϫ exchanger, which mediates HCO 3 Ϫ secretion (17,26). This exchanger in ␤-ICs was subsequently shown to be pendrin (SLC26A4) (22); it appears as an apical cap and clearly plays a role in acid-base regulation. However, other studies have shown that pendrin expression is also dependent on urinary Cl Ϫ excretion (11, 34) and, if unregulated, could cause hypertension (34). A study (21) of pendrin expression during acid-base disturbances revealed that the expression, mRNA, protein abundance, and number of pendrin-positive cells in rabbit kidneys were decreased after 3 days of acidosis. Simila...

show abstract

“…Abundant evidence now supports pendrin as an important regulatory transporter in the cortical collecting ducts, which responds briskly 18 in vivo and in vitro 16 to alterations in chloride intake 19 and to acid-base perturbations including metabolic alkalosis and acidosis 20 and respiratory acidosis 21 (Table 1). The main stimuli seem to be distal chloride delivery 22 and intracellular pH.…”

mentioning

confidence: 99%

It Is Chloride Depletion Alkalosis, Not Contraction Alkalosis

Luke

Galla

2012

Journal of the American Society of Nephrology

101

View full text Add to dashboard Cite

Maintenance of metabolic alkalosis generated by chloride depletion is often attributed to volume contraction. In balance and clearance studies in rats and humans, we showed that chloride repletion in the face of persisting alkali loading, volume contraction, and potassium and sodium depletion completely corrects alkalosis by a renal mechanism. Nephron segment studies strongly suggest the corrective response is orchestrated in the collecting duct, which has several transporters integral to acid-base regulation, the most important of which is pendrin, a luminal Cl/HCO 3 2 exchanger. Chloride depletion alkalosis should replace the notion of contraction alkalosis.

show abstract

Adaptation to metabolic acidosis and its recovery are associated with changes in anion exchanger distribution and expression in the cortical collecting duct

Cited by 42 publications

References 42 publications

Collecting Duct Intercalated Cell Function and Regulation

Collecting Duct Intercalated Cell Function and Regulation

Insights into acidosis-induced regulation of SLC26A4 (pendrin) and SLC4A9 (AE4) transporters using three-dimensional morphometric analysis of β-intercalated cells

It Is Chloride Depletion Alkalosis, Not Contraction Alkalosis

Contact Info

Product

Resources

About