Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identities of the apical Cl-/base exchangers in kidney proximal tubule and cortical collecting duct (CCD) cells remain unknown. Pendrin (PDS), which is expressed at high levels in the thyroid and its mutation causes Pendred's syndrome, is shown to be an anion exchanger. We investigated the renal distribution of PDS and its function. Our results demonstrate that pendrin mRNA expression in the rat kidney is abundant and limited to the cortex. Proximal tubule suspensions isolated from kidney cortex were highly enriched in pendrin mRNA. Immunoblot analysis studies localized pendrin to cortical brush-border membranes. Nephron segment RT-PCR localized pendrin mRNA to proximal tubule and CCD. Expression studies in HEK-293 cells demonstrated that pendrin functions in the Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange modes. The conclusion is that pendrin is an apical Cl-/base exchanger in the kidney proximal tubule and CCD and mediates Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange.
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PMID:Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex. 1120 11

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

Renal apical chloride-base exchangers are essential to electrolyte and acid-base homeostasis. Different functional isoforms of apical anion exchangers have been identified in kidney proximal tubule and cortical collecting duct. Included amongst these are the following: chloride-formate, chloride-oxalate, and chloride-hydroxyl exchangers in proximal tubule; and chloride-bicarbonate exchanger in cortical collecting duct. Chloride-formate exchange, which was first identified in kidney proximal tubule, works in parallel with the apical sodium-hydrogen exchanger, and is thought to reabsorb the bulk of luminal chloride. Despite numerous studies, the molecular identities of apical chloride-base exchangers have remained unknown. Recent studies have identified a new class of anion exchangers, including pendrin (encoded by the PDS gene) and downregulated in adenoma (DRA, encoded by the DRA gene). Pendrin is expressed in the kidney, whereas DRA is not. Functional studies indicate that pendrin can function in chloride-formate and chloride-base exchange modes. It is unlikely that pendrin is the apical chloride-formate exchanger in the kidney proximal tubule. However, it is the only molecule that has been shown to mediate chloride-formate exchange. In the present review, recent studies regarding the renal distribution and membrane localization of pendrin, and its functional properties, including its roles in chloride reabsorption and base excretion, are addressed.
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PMID:Molecular physiology of the renal chloride-formate exchanger. 1149 64

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

Pendrin is an apical Cl(-)/OH(-)/HCO(3)(-) exchanger in beta-intercalated cells (beta-ICs) of rat and mouse cortical collecting duct (CCD). However, little is known about its regulation in acid-base disorders. Here, we examined the regulation of pendrin in metabolic acidosis, a condition known to decrease HCO(3)(-) secretion in CCD. Rats were subjected to NH(4)Cl loading for 4 days, which resulted in metabolic acidosis. Apical Cl(-)/HCO(3)(-) exchanger activity in beta-ICs was determined as amplitude and rate of intracellular pH change when Cl was removed in isolated, microperfused CCDs. Intracellular pH was measured by single-cell digital ratiometric imaging using fluorescent pH-sensitive dye 2',7'-bis-(3-carboxypropyl)-5-(and-6)-carboxyfluorescein-AM. Pendrin mRNA expression in kidney cortex was examined by Northern blot hybridizations. Expression of pendrin protein was assessed by indirect immunofluorescence. Microperfused CCDs isolated from acidotic rats demonstrated approximately 60% reduction in apical Cl(-)/HCO(3)(-) exchanger activity in beta-ICs (P < 0.001 vs. control). Northern blot hybridizations indicated that the mRNA expression of pendrin in kidney cortex decreased by 68% in acidotic animals (P < 0.02 vs. control). Immunofluorescence labeling demonstrated significant reduction in pendrin expression in CCDs of acidotic rats. We conclude that metabolic acidosis decreases the activity of the apical Cl(-)/HCO(3)(-) exchanger in beta-ICs of the rat CCD by reducing the expression of pendrin. Adaptive downregulation of pendrin in metabolic acidosis indicates the important role of this exchanger in acid-base regulation in the CCD.
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PMID:Regulation of the apical Cl-/HCO-3 exchanger pendrin in rat cortical collecting duct in metabolic acidosis. 1238 88

Pendrin is an anion exchanger expressed in type B intercalated cells of the cortical collecting duct (CCD). Whether pendrin localizes to other nephron segments with intercalated cells is unknown. Moreover, whether pendrin is expressed in proximal tubule is debated. Thus the distribution of pendrin mRNA and protein expression in mouse kidney was investigated by using light and electron microscopic immunohistochemistry and quantitative real-time PCR. We observed that pendrin mRNA is expressed mainly in cortex. Within cortex, pendrin mRNA is at least fivefold higher in CCD and the connecting tubule (CNT) than in the other segments. Pendrin protein was observed in a subset of cells within the distal convoluted tubule as well as in type B and in non-A-non-B intercalated cells of the CNT and CCD. In type B intercalated cells, pendrin immunoreactivity was highest in apical cytoplasmic vesicles with little immunolabel along the apical plasma membrane. In non-A-non-B intercalated cells, intense pendrin immunoreactivity was detected along the apical plasma membrane. These differences in the subcellular distribution of pendrin immunolabel were confirmed by morphometric analysis. In conclusion, pendrin is expressed in the mouse distal convoluted tubule, CCD, and CNT along the apical plasma membrane of non-A-non-B intercalated cells and in subapical cytoplasmic vesicles of type B intercalated cells.
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PMID:Localization of pendrin in mouse kidney. 1238 26

Pendrin is an anion exchanger expressed along the apical plasma membrane and apical cytoplasmic vesicles of type B and of non-A, non-B intercalated cells of the distal convoluted tubule, connecting tubule, and cortical collecting duct. Thus, Pds (Slc26a4) is a candidate gene for the putative apical anion-exchange process of the type B intercalated cell. Because apical anion exchange-mediated transport is upregulated with deoxycorticosterone pivalate (DOCP), we tested whether Pds mRNA and protein expression in mouse kidney were upregulated after administration of this aldosterone analogue by using quantitative real-time polymerase chain reaction as well as light and electron microscopic immunolocalization. In kidneys from DOCP-treated mice, Pds mRNA increased 60%, whereas pendrin protein expression in the apical plasma membrane increased 2-fold in non-A, non-B intercalated cells and increased 6-fold in type B cells. Because pendrin transports HCO3- and Cl-, we tested whether DOCP treatment unmasks abnormalities in acid-base or NaCl balance in Pds (-/-) mice. In the absence of DOCP, arterial pH, systolic blood pressure, and body weight were similar in Pds (+/+) and Pds (-/-) mice. After DOCP treatment, weight gain and hypertension were observed in Pds (+/+) but not in Pds (-/-) mice. Moreover, after DOCP administration, metabolic alkalosis was more severe in Pds (-/-) than Pds (+/+) mice. We conclude that pendrin is upregulated with aldosterone analogues and is critical in the pathogenesis of mineralocorticoid-induced hypertension and metabolic alkalosis.
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PMID:Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: role of pendrin in mineralocorticoid-induced hypertension. 1292 56

Pendrin (Pds; Slc26A4) is a new anion exchanger that is believed to mediate apical Cl(-)/HCO(3)(-) exchange in type B and non-A-non-B intercalated cells of the connecting tubule and cortical collecting duct. Recently, it has been proposed that this transporter may be involved in NaCl balance and blood pressure regulation in addition to its participation in the regulation of acid-base status. The purpose of our study was to determine the regulation of Pds protein abundance during chronic changes in chloride balance. Rats were subjected to either NaCl, NH(4)Cl, NaHCO(3), KCl, or KHCO(3) loading for 6 days or to a low-NaCl diet or chronic furosemide administration. Pds protein abundance was estimated by semiquantitative immunoblotting in renal membrane fractions isolated from the cortex of treated and control rats. We observed a consistent inverse relationship between Pds expression and diet-induced changes in chloride excretion independent of the administered cation. Conversely, NaCl depletion induced by furosemide was associated with increased Pds expression. We conclude that Pds expression is specifically regulated in response to changes in chloride balance.
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PMID:The Cl-/HCO3- exchanger pendrin in the rat kidney is regulated in response to chronic alterations in chloride balance. 1716 96

Pendrin (Slc26a4) localizes to type B and non-A, non-B intercalated cells in the distal convoluted tubule, the connecting tubule, and the cortical collecting duct (CCD), where it mediates apical Cl(-)/HCO(3)(-) exchange. The purpose of this study was to determine whether angiotensin II increases transepithelial net chloride transport, J(Cl), in mouse CCD through a pendrin-dependent mechanism. J(Cl) and transepithelial voltage, V(T), were measured in CCDs perfused in vitro from wild-type and Slc26a4 null mice ingesting a NaCl-replete diet or a NaCl-replete diet and furosemide. In CCDs from wild-type mice ingesting a NaCl-replete diet, V(T) and J(Cl) were not different from zero either in the presence or absence of angiotensin II (10(-8) M) in the bath. Thus further experiments employed mice given the high-NaCl diet and furosemide to upregulate renal pendrin expression. CCDs from furosemide-treated wild-type mice had a lumen-negative V(T) and absorbed Cl(-). With angiotensin II in the bath, Cl(-) absorption doubled although V(T) did not become more lumen negative. In contrast, in CCDs from furosemide-treated Slc26a4 null mice, Cl(-) secretion and a V(T) of approximately 0 were observed, neither of which changed with angiotensin II application. Inhibiting ENaC with benzamil abolished V(T) although J(Cl) fell only approximately 50%. Thus substantial Cl(-) absorption is observed in the absence of an electromotive force. Attenuating apical anion exchange with the peritubular application of the H(+)-ATPase inhibitor bafilomycin abolished benzamil-insensitive Cl(-) absorption. In conclusion, angiotensin II increases transcellular Cl(-) absorption in the CCD through a pendrin- and H(+)-ATPase-dependent process.
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PMID:Angiotensin II increases chloride absorption in the cortical collecting duct in mice through a pendrin-dependent mechanism. 1716 96

Pendrin is an apical anion exchanger found in type B and nonA-nonB intercalated cells that is involved in bicarbonate secretion. The purpose of this study was to establish the origin and fate of pendrin-positive intercalated cells in the mouse kidney. Using immunohistochemistry, we found that pendrin-positive cells first appeared in the connecting tubule at embryonic day 14 (E14) and subsequently in the medullary collecting duct at E18. Most of the pendrin-positive cells in the connecting tubule were nonA-nonB intercalated cells, wheras those in the medullary collecting duct were type B intercalated cells. In the cortical collecting duct, pendrin-positive cells appeared in the inner part at day 4 after birth and in the outer part at day 7. Pendrin-positive cells gradually disappeared by apoptosis from the inner part of the medullary collecting duct two weeks after birth. Using 5-bromo-2'deoxy-uridine (BrdU) to follow cell proliferation, we determined that selective proliferation of pendrin-positive intercalated cells does not occur; instead, these cells may arise from undifferentiated precursor cells from separate foci, one in the connecting tubule and one in the collecting duct.
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PMID:Origin and fate of pendrin-positive intercalated cells in developing mouse kidney. 1785 46


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