Regulation of AE1 anion exchanger and H+-ATPase in rat cortex by acute metabolic acidosis and alkalosis

Sabolić, Ivan; Brown, Dennis; Gluck, Stephen L.; Alper, Seth L.

doi:10.1038/ki.1997.16

Cited by 120 publications

(109 citation statements)

References 30 publications

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“…The presence of intermediate cells raises many questions about the origin and diversity of these cell types, and some AE1-negative intercalated cells display bipolar and/or a diffuse cytoplasmic distribution of the V-ATPase (2, 3) and some cortical intercalated cell types express pendrin and the V-ATPase on the apical surface (the so-called non-A non-B type) (4). Induction of metabolic acidosis or alkalosis produces a profound change in the population distribution of these different cell types with acidosis shifting the distribution to the type with apical ATPase, whereas alkalosis increases the number of canonical β-cells at the expense of α-cells (5,6). That an individually identified β-intercalated cell actually converts to an α-intercalated cell was provided more recently when we found that its exposure to a basolateral low pH medium caused a significant fraction of such cells, which had an apical Cl:HCO3 exchanger to convert to ones with basolateral Cl:HCO 3 exchangers (7).…”

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confidence: 99%

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Gao

Eladari

Leviel

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Acid–base transport in the renal collecting tubule is mediated by two canonical cell types: the β-intercalated cell secretes HCO 3 by an apical Cl:HCO 3 named pendrin and a basolateral vacuolar (V)-ATPase. Acid secretion is mediated by the α-intercalated cell, which has an apical V-ATPase and a basolateral Cl:HCO 3 exchanger (kAE1). We previously suggested that the β-cell converts to the α-cell in response to acid feeding, a process that depended on the secretion and deposition of an extracellular matrix protein termed hensin (DMBT1). Here, we show that deletion of hensin from intercalated cells results in the absence of typical α-intercalated cells and the consequent development of complete distal renal tubular acidosis (dRTA). Essentially all of the intercalated cells in the cortex of the mutant mice are canonical β-type cells, with apical pendrin and basolateral or diffuse/bipolar V-ATPase. In the medulla, however, a previously undescribed cell type has been uncovered, which resembles the cortical β-intercalated cell in ultrastructure, but does not express pendrin. Polymerization and deposition of hensin (in response to acidosis) requires the activation of β1 integrin, and deletion of this gene from the intercalated cell caused a phenotype that was identical to the deletion of hensin itself, supporting its critical role in hensin function. Because previous studies suggested that the conversion of β- to α-intercalated cells is a manifestation of terminal differentiation, the present results demonstrate that this differentiation proceeds from HCO 3 secreting to acid secreting phenotypes, a process that requires deposition of hensin in the ECM.

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confidence: 99%

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Gao

Eladari

Leviel

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…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). Overall, induction of chronic metabolic acidosis increases the proportion of type A intercalated cells while metabolic alkalosis causes an increase of type B intercalated cells (7,45,46). Moreover, mice with a hensin defect in intercalated cells indeed developed metabolic acidosis.…”

Section: Intercalated Cell Distribution Nomenclature Morphology Anmentioning

confidence: 99%

Collecting Duct Intercalated Cell Function and Regulation

Roy¹,

Al‐bataineh²,

Pastor-Soler

2015

Clinical Journal of the American Society of Nephrology

207

213

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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.

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“…For example, the V-ATPase is regulated by several pathways, which involve CO 2 , phosphatidylinositol 3-kinase, aldolase, phosphofructokinase, actin, microtubules, and angiotensin in a variety of mammalian cellular systems (20 -27). The number of VATPases at the apical membrane of intercalated cells in the kidney increases rapidly under conditions of systemic acidosis (28,29). Acidosis also induces H ϩ secretion via the V-ATPase through changes in intracellular [Ca 2ϩ ] concentration, calmodulin activation, the cytoskeleton, and by altering the rate of endocytosis and exocytosis in kidney cells (30).…”

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confidence: 99%

PKA Regulates Vacuolar H+-ATPase Localization and Activity via Direct Phosphorylation of the A Subunit in Kidney Cells

Alzamora

Thali

Gong

et al. 2010

Journal of Biological Chemistry

111

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Acid secretion in epithelial cells is actively regulated by environmental signals, although the mechanisms by which these cues are translated into activation of H ϩ transport pathways remains the subject of intense research (11,(15)(16)(17)(18)(19). For example, the V-ATPase is regulated by several pathways, which involve CO 2 , phosphatidylinositol 3-kinase, aldolase, phosphofructokinase, actin, microtubules, and angiotensin in a variety of mammalian cellular systems (20 -27). The number of VATPases at the apical membrane of intercalated cells in the kidney increases rapidly under conditions of systemic acidosis (28, 29). Acidosis also induces H ϩ secretion via the V-ATPase through changes in intracellular [Ca 2ϩ ] concentration, calmodulin activation, the cytoskeleton, and by altering the rate of endocytosis and exocytosis in kidney cells (30).We and others have shown that regulation of the V-ATPase at the apical membrane of intercalated and clear cells is tightly linked to alkaline luminal pH, HCO 3 Ϫ , carbonic anhydrase activity, activation of the soluble adenylyl cyclase (sAC),

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Regulation of AE1 anion exchanger and H+-ATPase in rat cortex by acute metabolic acidosis and alkalosis

Cited by 120 publications

References 30 publications

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Collecting Duct Intercalated Cell Function and Regulation

PKA Regulates Vacuolar H+-ATPase Localization and Activity via Direct Phosphorylation of the A Subunit in Kidney Cells

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