Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pendrin is an anion transporter encoded by the PDS/Pds gene. In humans, mutations in PDS cause the genetic disorder Pendred syndrome, which is associated with deafness and goiter. Previous studies have shown that this gene has a relatively restricted pattern of expression, with PDS/Pds mRNA detected only in the thyroid, inner ear, and kidney. The present study examined the distribution and function of pendrin in the mammalian kidney. Immunolocalization studies were performed using anti-pendrin polyclonal and monoclonal antibodies. Labeling was detected on the apical surface of a subpopulation of cells within the cortical collecting ducts (CCDs) that also express the H(+)-ATPase but not aquaporin-2, indicating that pendrin is present in intercalated cells of the CCD. Furthermore, pendrin was detected exclusively within the subpopulation of intercalated cells that express the H(+)-ATPase but not the anion exchanger 1 (AE1) and that are thought to mediate bicarbonate secretion. The same distribution of pendrin was observed in mouse, rat, and human kidney. However, pendrin was not detected in kidneys from a Pds-knockout mouse. Perfused CCD tubules isolated from alkali-loaded wild-type mice secreted bicarbonate, whereas tubules from alkali-loaded Pds-knockout mice failed to secrete bicarbonate. Together, these studies indicate that pendrin is an apical anion transporter in intercalated cells of CCDs and has an essential role in renal bicarbonate secretion.
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PMID:Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion. 1127 45

Recent studies have demonstrated that a novel anion exchanger, pendrin, is expressed in the apical domain of type B intercalated cells in the mammalian collecting duct. The purpose of this study was 1) to determine the expression and distribution of pendrin along the collecting duct and connecting tubule of mouse and rat kidney and establish whether pendrin is expressed in the non-A-non-B intercalated cells and 2) to determine the intracellular localization of pendrin in the different populations of intercalated cells by immunoelectron microscopy. A peptide-derived affinity-purified antibody was generated that specifically recognized pendrin in immunoblots of rat and mouse kidney. Immunohistochemistry and confocal laser scanning microscopy demonstrated the presence of pendrin in apical domains of all type B intercalated cells in mouse and rat connecting tubule and collecting duct. In addition, strong pendrin immunostaining was observed in non-A-non-B intercalated cells. There was no labeling of type A intercalated cells. Immunoelectron microscopy demonstrated that pendrin was located in the apical plasma membrane and intracellular vesicles of both type B intercalated cells and non-A-non-B cells; the latter was identified by the presence of H(+)-ATPase in the apical plasma membrane. The results of this study demonstrate that both pendrin and H(+)-ATPase are expressed in the apical plasma membrane of non-A-non-B intercalated cells, suggesting that these cells are capable of both HCO and proton secretion. Furthermore, the presence of pendrin in both the apical plasma membrane and the apical intracellular vesicles of type B and non-A-non-B intercalated cells suggests that HCO secretion may be regulated by trafficking of pendrin between the two membrane compartments.
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PMID:Immunocytochemical localization of pendrin in intercalated cell subtypes in rat and mouse kidney. 1221 66

Pendrin is an anion exchanger in the cortical collecting duct of the mammalian nephron that appears to mediate apical Cl(-)/HCO3(-) exchange in bicarbonate-secreting intercalated cells. The goals of this study were to determine 1) if pendrin immunoreactivity was present in the gills of a euryhaline elasmobranch (Atlantic stingray, Dasyatis sabina), and 2) if branchial pendrin immunoreactivity was influenced by environmental salinity. Immunoblots detected pendrin immunoreactivity in Atlantic stingray gills; pendrin immunoreactivity was greatest in freshwater stingrays compared with freshwater stingrays acclimated to seawater (seawater acclimated) and marine stingrays. Using immunohistochemistry, pendrin-positive cells were detected on both gill lamellae and interlamellar regions of freshwater stingrays but were more restricted to interlamellar regions in seawater-acclimated and marine stingray gills. Pendrin immunolabeling in freshwater stingray gills was more apical, discrete, and intense compared with seawater-acclimated and marine stingrays. Regardless of salinity, pendrin immunoreactivity occurred on the apical region of cells rich with basolateral vacuolar-proton-ATPase, and not in Na(+)-K(+)-ATPase-rich cells. We suggest that a pendrin-like transporter may contribute to apical Cl(-)/HCO3(-) exchange in gills of Atlantic stingrays from both freshwater and marine environments.
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PMID:Pendrin immunoreactivity in the gill epithelium of a euryhaline elasmobranch. 1222 69

The increasing number of available genetically manipulated mice makes it necessary to develop tools and techniques for examining the phenotypes of these animals. We have developed a straightforward and rapid method for the isolation of large quantities of single tubule fragments from the mouse kidney. Immunohistochemistry, electron microscopy, and fluorescence microscopy were used to evaluate the viability, functional characteristics, and morphology of proximal tubules (PT), and collecting ducts from cortex (CCD) and inner stripe of the outer medulla (ISOMCD). Tubules were isolated using a modified collagenase digestion technique, and selected under light microscopy for experimentation. Electron microscopy and trypan blue exclusion showed that a large portion of unselected proximal tubules were damaged by the digestion procedure. The selected tubules, however, all excluded trypan blue, indicating that the plasma membrane had remained intact. Immunocytochemistry on isolated CCD showed normal distribution of H(+)-ATPase, pendrin, and anion exchanger-1 (AE-1) staining. The pH-sensitive dye 2',7'-bis(2-carboxylethyl)-5(6)-carboxyfluorescein (BCECF) was used to measure Na(+)-dependent and -independent intracellular pH (pH(i)) recovery rates in PT, and in single intercalated cells of CCD and ISOMCD fragments. Na(+)-dependent pH(i)-recovery was 0.144+/-0.008 (PT), 0.182+/-0.013 (CCD), and 0.112+/-0.010 pH units/min. (ISOMCD). Na(+)-independent pH(i) recovery was found in all three segments (PT: 0.021+/-0.002, CCD: 0.037+/-0.002, ISOMCD: 0.033+/-0.002 pH units/min) and was sensitive to concanamycin. In summary, we have developed a new technique for rapid and straightforward preparation of large quantities of defined tubule fragments from mouse kidney. Using this technique, the first measurements of plasma membrane vacuolar H(+)-ATPase activities in mouse PT and collecting duct were made. This technique will facilitate further characterization of kidney function in normal and genetically manipulated animals.
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PMID:A rapid enzymatic method for the isolation of defined kidney tubule fragments from mouse. 1274 63

Prolonged lithium treatment of humans and rodents often results in hyperchloremic metabolic acidosis. This is thought to be caused by diminished net H+ secretion and/or excessive back-diffusion of acid equivalents. To explore whether lithium treatment is associated with changes in the expression of key renal acid-base transporters, semiquantitative immunoblotting and immunocytochemistry were performed using kidneys from lithium-treated (n = 6) and control (n = 6) rats. Rats treated with lithium for 28 days showed decreased urine pH, whereas no significant differences in blood pH and plasma HCO3- levels were observed. Immunoblot analysis revealed that lithium treatment induced a significant increase in the expression of the H+-ATPase (B1-subunit) in cortex (190 +/- 18%) and inner stripe of the outer medulla (190 +/- 9%), and a dramatic increase in inner medulla (900 +/- 104%) in parallel to an increase in the expression of type 1 anion exchanger (400 +/- 40%). This was confirmed by immunocytochemistry and immunoelectron microscopy, which also revealed increased density of intercalated cells. Moreover, immunoblotting and immunocytochemistry revealed a significant increase in the expression of the type 1 electrogenic Na+-HCO3- cotransporter (NBC) in cortex (200 +/- 23%) and of the electroneutral NBCn1 in inner stripe of the outer medulla (250 +/- 54%). In contrast, there were no changes in the expression of Na+/H+ exchanger-3 or of the Cl-/HCO3- exchanger pendrin. These results demonstrate that the expression of specific renal acid-base transporters is markedly altered in response to long-term lithium treatment. This is likely to represent direct or compensatory effects to increase the capacity for HCO3- reabsorption, NH4+ reabsorption, and proton secretion to prevent the development of systemic metabolic acidosis.
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PMID:Altered expression of renal acid-base transporters in rats with lithium-induced NDI. 1294 21

The kidney plays a major role in maintaining and controlling systemic acid-base homeostasis by reabsorbing bicarbonate and secreting protons and acid-equivalents, respectively. During postnatal kidney development and adaptation to changing diets, plasma bicarbonate levels are increasing, the capacity for urinary acidification maturates, and the final morphology and distribution of intercalated cells is achieved. In adult kidney, at least two types of intercalated cells (IC) are found along the collecting duct characterised either by the expression of AE1 (type A IC) or pendrin (non-type A IC) where non-type A IC are found only in the convoluted distal tubule, connecting tubule and cortical collecting duct. Here we investigated in mouse kidney the relative mRNA abundance, protein expression levels and distribution of several proteins involved in renal acid-base transport, namely, the Na(+)/HCO(3)(-) cotransporter NBC1 (SLC4A4), the Na(+)/H(+)-exchanger NHE3 (SLC9A3), two subunits of the vacuolar H(+)-ATPase [ATP6V0A4 (a4), ATP6V1B1 (B1)], the Cl(-)/HCO(3)(-) exchangers AE1 (SLC4A1) and pendrin (SLC26A4). Relative mRNA abundance of all transport proteins was lowest at day 3 after birth and increased thereafter in parallel with protein levels. The numbers of type A and non-type A IC in the cortical collecting duct (CCD) increased from day 3 to days 18 and 24, whereas the number of IC in the CCD with apical staining for the vacuolar H(+)-ATPase subunits a4 and B1 decreased from day 3 to days 18 and 24, respectively. In addition, cells with characteristics of non-type A IC (pendrin expression, basolateral expression of vacuolar H(+)-ATPase subunits) were found in the inner and outer medulla 3 days after birth but were absent from the medulla of 24-day-old mice. Taken together, these results demonstrate massive changes in mRNA and protein expression levels of several acid-base transporters during postnatal kidney maturation and also show changes in intercalated cell phenotype in the medulla during these processes.
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PMID:Postnatal expression of transport proteins involved in acid-base transport in mouse kidney. 1475 80

The endolymph in the endolymphatic sac (ES) is acidic (pH 6.6-7). Maintaining this acidic lumen is believed to be important for the normal function of the ES. The acid-base regulation mechanisms of the ES are unknown. Here we investigated the expression patterns of acid-base regulators, including vacuolar (v)H+-ATPase (proton pump), carbonic anhydrase (CA) II, and pendrin in the murine ES epithelium by immunohistochemistry (IHC) and compared their expression patterns by double immunostaining. We found that pendrin and vH+-ATPase were co-localized in the apical membrane of a specific type of ES epithelial cell. Pendrin- and vH+-ATPase-positive cells also expressed cytoplasmic CA II. Co-expression of pendrin, vH+-ATPase, and CA II in the same subgroup of ES cells suggests that this specific type of ES cell is responsible for the acid-base balance processes in the ES and pendrin, vH+-ATPase, and CA II are involved in these processes.
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PMID:Co-expression of pendrin, vacuolar H+-ATPase alpha4-subunit and carbonic anhydrase II in epithelial cells of the murine endolymphatic sac. 1538 84

Slc26a4 (Pds) encodes pendrin, a Cl(-)/HCO(3)(-) exchanger expressed in the apical region of type B and non-A, non-B cells, which mediates secretion of OH(-) equivalents. Thus genetic disruption of Slc26a4 leads to systemic alkalosis in some treatment models. However, humans and mice with genetic disruption of Slc26a4 have normal acid-base balance under basal conditions. Thus we asked: 1) Is net acid excretion altered in Slc26a4 (-/-) mice under basal conditions? 2) In the absence of pendrin-mediated OH(-) secretion, are increases in intracellular and systemic pH minimized through changes in intercalated cell subtype abundance or intercalated cell H(+)/OH(-) transporter expression? To answer these questions, net acid excretion and H(+)/OH(-) transporter expression were examined in Slc26a4 (-/-) and Slc26a4 (+/+) mice using balance studies, immunolocalization, and immunoblotting. Excretion of ammonium, titratable acid, and citrate were the same in Slc26a4 null and wild-type mice. However, urinary pH and Pco(2) were much lower in Slc26a4 null relative to wild-type mice due to reduced urinary buffering of secreted H(+) by HCO(3)(-). Abundance of non-A, but not type A intercalated cells, was reduced within the cortical collecting ducts of Slc26a4 null mice. Moreover, kidneys from Slc26a4 null mice had reduced H(+)-ATPase, NBC3 and RhBG total protein expression, particularly within type B and non-A, non-B intercalated cells, although RhCG protein expression was unchanged. Reduced intercalated cell H(+)/OH(-) transporter expression is observed in Slc26a4 null mice, which likely attenuates the rise in intracellular and systemic pH expected with genetic disruption of Slc26a4.
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PMID:Intercalated cell H+/OH- transporter expression is reduced in Slc26a4 null mice. 1614 65

The post-macula densa segments of the renal tubule--that is, the distal convoluted tubule, connecting tubule, and collecting duct--play a central role in determining final urine sodium excretion. The major regulated sodium transporters and channels in these cell types include the thiazide-sensitive (Na-Cl) cotransporter (NCC), the epithelial sodium channel (ENaC), and Na-K-ATPase. Furthermore, although not involved in sodium reabsorption, the anion exchanger, pendrin, and the basolateral bumetanide-sensitive Na-K-2Cl cotransporter (NKCC1 or BSC2) have roles in blood-volume maintenance. Mutations in several of these major sodium transporters, channel subunits, and their regulatory proteins have been linked to human diseases such as Liddle's syndrome, Gitelman's syndrome, and Gordon's syndrome, emphasizing the need for appropriate regulation of sodium at these sites for maintenance of sodium balance and normotension.
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PMID:Sodium transporters in the distal nephron and disease implications. 1667 50

Recent studies of the distribution of PKC isoenzymes in the mouse kidney demonstrated that PKC-alpha, -beta(I), and -delta are expressed in intercalated cells. The purpose of this study was to identify the intercalated cell subtypes that express the different PKC isoenzymes and determine the location of the PKC isoenzymes within these cells. Adult C57BL/6 mice kidney tissues were processed for multiple-labeling immunohistochemistry. Antibodies against the vacuolar H(+)-ATPase and pendrin were used to identify intercalated cell subtypes, whereas antibodies against calbindin D(28K) and aquaporin-2 (AQP2) were used to identify connecting tubule cells and principal cells of the collecting duct, respectively. Within type A intercalated cells, PKC-delta was highly expressed in the apical part of the cells, whereas immunoreactivity for both PKC-alpha and PKC-beta(I) was weak. Type B intercalated cells exhibited strong expression of PKC-alpha, -beta(I), and -delta. PKC-alpha and -beta(I) were localized throughout the cytoplasm, whereas PKC-delta was restricted to the basal domain. Within non-A-non-B cells, immunoreactivity for both PKC-alpha and PKC-beta(I) was high in intensity and localized diffusely in the cytoplasm, whereas PKC-delta was localized in the apical part of the cells. None of the PKC isoenzymes (PKC-alpha, -beta(I), or -delta) were expressed in the calbindin D(28K)-positive connecting tubule cells. Within AQP2-positive principal cells of the collecting duct, PKC-alpha was expressed on the basolateral plasma membrane, but no significant staining was detected for PKC-beta(I) and -delta. In summary, this study demonstrates distinct and differential expression patterns of PKC-alpha, -beta(I), and -delta in the three subtypes of intercalated cells in the mouse kidney.
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PMID:Expression of protein kinase C isoenzymes alpha, betaI, and delta in subtypes of intercalated cells of mouse kidney. 1673 62


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