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)

Previous studies have suggested the presence of an H(+)-K(+)-ATPase in rat cortical and medullary intercalated cells with similar properties to the gastric proton pump. The purpose of this study was to determine the functional contribution of an H(+)-K(+)-adenosinetriphosphatase(ATPase) to total CO2 (tCO2) transport along the rat collecting duct. After baseline determination of tCO2 transport in isolated perfused collecting duct segments, Sch 28080 (10 microM) was added to either the perfusate or bath. When Sch 28080 was added to the perfusate, there was no effect in the cortical collecting duct (CCD, 20.8 +/- 6.7 vs. 25.3 + 3.0 pmol.mm-1.min-1), but a marked decrease in tCO2 absorption was effected in both the outer medullary (OMCD, 37.6 + 6.2 vs. 10.7 +/- 4.1 pmol.mm-1.min-1) and initial inner medullary collecting duct (IMCD1, 34.4 +/- 8.1 vs. 16.2 +/- 5.6 pmol.mm-1.min-1). In the CCD from rats with acute alkalosis in vivo, Sch 28080 added to the bath inhibited tCO2 secretion in the CCD (-17.1 +/- 4.4 vs 3.5 + 3.3 pmol.mm-1.min-1). These findings suggest that 1) H(+)-K(+)-ATPase is important in tCO2 absorption in the OMCD and IMCD1 and in tCO2 secretion in the CCD, 2) HCO3(-)-absorbing intercalated cells differ functionally in the cortex and medulla, 3) HCO3- secretion is not the reverse process of HCO3- absorption in the CCD, and 4) H(+)-K(+)-ATPase is important in distal acidification under normal and altered acid-base conditions.
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PMID:H(+)-K(+)-ATPase activity in rat collecting duct segments. 131 8

The intercalated cells of the kidney collecting duct are specialized for physiologically regulated proton transport. In these cells, a vacuolar H(+)-ATPase is expressed at enormous levels in a polarized distribution on the plasma membrane, enabling it to serve in transepithelial H+ transport. In contrast, in most eukaryotic cells, vacuolar H(+)-ATPases reside principally in intracellular compartments to effect vacuolar acidification. To investigate the basis for the selective amplification of the proton pump in intercalated cells, we isolated and sequenced cDNA clones for two isoforms of the approximately 56-kDa subunit of the H(+)-ATPase and examined their expression in various tissues. The predicted amino acid sequence of the isoforms was highly conserved in the internal region but diverged in the amino and carboxyl termini. mRNA hybridization to a cDNA probe for one isoform (the "kidney" isoform) was detected only in kidney cortex and medulla, whereas mRNA hybridization to the other isoform of the approximately 56-kDa subunit and to the H(+)-ATPase 31-kDa subunit was found in the kidney and other tissues. Immunocytochemistry of rat kidney with an antibody specific to the kidney isoform revealed intense staining only in the intercalated cells. Staining was absent from proximal tubule and thick ascending limb, where H(+)-ATPase was detected with a monoclonal antibody to the 31-kDa subunit of the H(+)-ATPase. This example of specific amplification of an isoform of one subunit of the vacuolar H(+)-ATPase being limited to a specific cell type suggests that the selective expression of the kidney isoform of the approximately 56-kDa subunit may confer the capacity for amplification and other specialized functions of the vacuolar H(+)-ATPase in the renal intercalated cell.
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PMID:Selectively amplified expression of an isoform of the vacuolar H(+)-ATPase 56-kilodalton subunit in renal intercalated cells. 137 1

Endocytic vesicles that are involved in the vasopressin-stimulated recycling of water channels to and from the apical membrane of kidney collecting duct principal cells were isolated from rat renal papilla by differential and Percoll density gradient centrifugation. Fluorescence quenching measurements showed that the isolated vesicles maintained a high, HgCl2-sensitive water permeability, consistent with the presence of vasopressin-sensitive water channels. They did not, however, exhibit ATP-dependent luminal acidification, nor any N-ethylmaleimide-sensitive ATPase activity, properties that are characteristic of most acidic endosomal compartments. Western blotting with specific antibodies showed that the 31- and 70-kD cytoplasmically oriented subunits of the vacuolar proton pump were not detectable in these apical endosomes from the papilla, whereas they were present in endosomes prepared in parallel from the cortex. In contrast, the 56-kD subunit of the proton pump was abundant in papillary endosomes, and was localized at the apical pole of principal cells by immunocytochemistry. Finally, an antibody that recognizes the 16-kD transmembrane subunit of oat tonoplast ATPase cross-reacted with a distinct 16-kD band in cortical endosomes, but no 16-kD band was detectable in endosomes from the papilla. This antibody also recognized a 16-kD band in affinity-purified H+ ATPase preparations from bovine kidney medulla. Therefore, early endosomes derived from the apical plasma membrane of collecting duct principal cells fail to acidify because they lack functionally important subunits of a vacuolar-type proton pumping ATPase, including the 16-kD transmembrane domain that serves as the proton-conducting channel, and the 70-kD cytoplasmic subunit that contains the ATPase catalytic site. This specialized, non-acidic early endosomal compartment appears to be involved primarily in the hormonally induced recycling of water channels to and from the apical plasma membrane of vasopressin-sensitive cells in the kidney collecting duct.
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PMID:Apical endosomes isolated from kidney collecting duct principal cells lack subunits of the proton pumping ATPase. 138 76

The inner medullary collecting duct (IMCD) is the most distal portion of the nephron and plays an important role in urinary net acid excretion. The terminal or distal two thirds of the IMCD is lined by a single cell type, now termed the IMCD cell, which not only secretes protons, but transports sodium and potassium and responds to many hormones. The IMCD may account for greater than 50% of the excreted acid under control conditions and, during acidosis, absolute acid secretion may increase fivefold. Conversely, during alkalemia, acid secretion by this segment is abolished. Thus, the IMCD responds appropriately to perturbations in systemic acid-base balance. Furthermore, models of renal tubular acidosis have been demonstrated along this nephron segment. Three transporters that are important in acid-base control, the Na+/H+ and the Cl-/HCO3- exchanger and an active proton pump, presumably an H(+)-adenosine phosphatase (ATPase), have been demonstrated in IMCD cells. The former two are situated in the basolateral membrane, while the latter is situated in the apical membrane. Only the proton pump is responsible for actual acid addition to the urine. The intracellular mechanisms that modulate the proton pump are just beginning to be defined. It is likely that acid secretory activity involves exocytic insertion of additional pumps, and is dependent on cell pH changes, which are the primary signal, and on changes in intracellular calcium concentration and calmodulin activity, which are the second messengers.
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PMID:Regulation of acidification in the rat inner medullary collecting duct. 165 87

Antidiuretic hormone (ADH) stimulation of toad bladder granular cells rapidly increases the osmotic water permeability (Pf) of their apical membranes by insertion of highly selective water channels. Before ADH stimulation, these water channels are stored in large cytoplasmic vesicles called aggrephores. ADH causes aggrephores to fuse with the apical membrane. Termination of ADH stimulation results in prompt endocytosis of water channel-containing membranes via retrieval of these specialized regions of apical membrane. Protein components of the ADH water channel contained within these retrieved vesicles would be expected to be integral membrane protein(s) that span the vesicle's lipid bilayer to create narrow aqueous channels. Our previous work has identified proteins of 55 (actually a 55/53-kDa doublet), 17, 15, and 7 kDa as candidate ADH water channel components. We now have investigated these candidate ADH water channel proteins in purified retrieved vesicles. These vesicles do not contain a functional proton pump as assayed by Western blots of purified vesicle protein probed with anti-H(+)-ATPase antisera. Approximately 60% of vesicle protein is accounted for by three protein bands of 55, 53, and 46 kDa. Smaller contributions to vesicle protein are made by the 17- and 15-kDa proteins. Triton X-114-partitioning analysis shows that the 55, 53, 46, and 17 kDa are integral membrane proteins. Vectorial labeling analysis with two membrane-impermeant reagents shows that the 55-, 53-, and 46-kDa protein species span the lipid bilayer of these vesicles. Thus the 55-, 53-, and 46-kDa proteins possess characteristics expected for ADH water channel components. These data show that the 55- and 53- and perhaps the 46-, 17-, and 15-kDa proteins are likely components of aqueous transmembrane pores that constitute ADH water channels contained within these vesicles.
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PMID:Quantitation and topography of membrane proteins in highly water-permeable vesicles from ADH-stimulated toad bladder. 183 Apr 55

Unilateral ureteral obstruction results in marked changes in renal function throughout the nephron, including impaired acid and potassium secretion and salt wastage. The nephron site believed responsible for the acidification defect is the collecting duct. It has been presumed, although not demonstrated, that the cellular mechanism for the acidification defect is both a decrease in transepithelial voltage and a decrease in activity of the proton pump located at the luminal membrane. The mechanism for the abnormalities in sodium handling are thought due to alterations in Na-K ATPase activity. Our laboratory has recently mapped the profile of the N-ethylmaleimide (NEM)-sensitive ATPase and Na-K ATPase in microdissected rat nephron, documenting their presence throughout much of the nephron. In animals with acute unilateral ureteral obstruction for 18 to 24 hours, we measured NEM-sensitive ATPase and Na-K ATPase activities in several nephron sites. In all nephron segments Na-K ATPase activity was markedly decreased. In the medullary collecting duct, NEM-sensitive ATPase activity was also markedly reduced in animals with acute ureteral obstruction; in the cortical collecting duct, activity fell significantly, but to a lesser degree than was observed in the medullary collecting duct. NEM-sensitive ATPase activity was unchanged from control in the proximal convoluted tubule and in the medullary thick ascending limb; in the cortical thick ascending limb enzyme activity increased. These results demonstrate a change in both Na-K ATPase and NEM-sensitive ATPase activities as a direct consequence of a defect known to result in salt wastage and an acidification defect in humans and animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzyme activity in obstructive uropathy: basis for salt wastage and the acidification defect. 215 50

Changes in cytosolic calcium concentration (Cai2+) have been implicated in the regulation of intracellular pH (pHi) in several cell types. In the present study we investigated the mechanism by which an increase in Cai2+ stimulates H+ secretion and a rise in pHi in cultured rat inner medullary collecting duct (IMCD) cells. Confluent monolayers were made quiescent by incubation for 24 h in 0.1% serum before study. Changes in pHi and Cai2+ were measured with the fluorescent probes, 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF) and fura-2. In nominally bicarbonate-free media containing 110 mM Na+ and 1 mM Ca2+, addition of the Ca2+ inophore, ionomycin (10 microM), produced a biphasic response in pHi, a transient acidification from 7.29 +/- 0.07 to 7.12 +/- 0.05 at 2 min followed by a sustained alkalinization to a steady-state value of 7.51 +/- 0.10 at 10 min. The rate of alkalinization was dose dependent. The alkalinization was not affected by 1 mM amiloride, removal of extracellular Na+, or by the proton pump inhibitor, N-ethyl maleimide (NEM). Metabolic energy was not required, but removal of extracellular Ca2+ prevented the alkalinization. By use of the fluorescent probe bisoxonol to assess membrane potential, ionomycin was shown to cause depolarization under the same experimental conditions as those for alkalinization. The Ca2+-induced alkalinization was mimicked by cell depolarization (induced by raising extracellular K+ in the presence of valinomycin 1 microM). We conclude that changes in Cai2+ are important in the regulation of pHi in the IMCD. Ca2+-induced cell alkalinization may be mediated by changes in membrane ionic conductance.
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PMID:Effect of increases in cytosolic Ca2+ on inner medullary collecting duct cell pH. 276 21

The distribution of vacuolar H+ATPase in rat kidney was examined by immunocytochemistry using affinity-purified antibodies against the 31-, 56-, and 70-kD subunits of the bovine kidney proton pump. Proximal convoluted tubules were labeled over apical plasma membrane invaginations, and in the initial part of the thin descending limb, apical and basolateral plasma membranes were moderately stained. Thick ascending limbs and distal convoluted tubules were apically stained although the intensity was greater in the distal convoluted tubule. Collecting duct principal cells were virtually unlabeled, but intercalated cells had intense staining with an apical, basolateral or diffuse pattern in the cortex, and exclusively apical staining in the medulla. These results (a) show the presence of an H+ATPase in the apical plasma membrane of the proximal tubule that may contribute to H+ transport in this segment; (b) provide direct evidence that the intercalated cell contains most of the H+ATPase detectable in the collecting duct, supporting its proposed role in H+ transport; (c) demonstrate that subpopulations of cortical intercalated cells have opposite polarities of an H+ATPase, consistent with the presence of both proton- and bicarbonate-secreting cells; and (d) suggest a role for the H+ATPase in acid/base regulation or H+ transport in segments other than the collecting duct and the proximal tubule.
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PMID:Localization of a proton-pumping ATPase in rat kidney. 290 51

Ammonium is the most important component of renal acid excretion. A reduced rate of ammonium excretion is the common feature of the group of diseases called distal renal tubular acidosis. We have presented an alternative approach to patients with distal acidification defects based upon the pathophysiology of these disorders. Accordingly, the purpose of this review is to describe a revised classification based on our current understanding of collecting duct hydrogen ion secretion and ammonium addition to the lumen of the distal nephron. We have subdivided these defects into four groups: disorders of the collecting duct proton pump (pump defects); failure to generate and/or maintain an appropriate electrical gradient to favor hydrogen ion secretion (voltage defects); back-leak of hydrogen ions across an abnormally permeable collecting duct membrane (gradient defects), and diminished availability of NH3 in this nephron segment (NH3 defects). These four subtypes can be identified by measuring the urine pH and PCO2 under appropriate circumstances and evaluating the renal excretion of ammonium and potassium.
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PMID:Distal renal tubular acidosis syndromes: a pathophysiological approach. 397 76

The outer medullary collecting duct which is composed of both principal and intercalated cells is involved in hydrogen ion secretion. In the turtle urinary bladder stimulation of hydrogen ion secretion is associated with ultrastructural changes in the mitochondria-rich cells, suggesting that membrane and possibly a proton pump are being transferred from apical tubulovesicular structures and inserted into the apical plasma membrane. Since the intercalated cells resemble the mitochondria-rich cells, this study was initiated to determine whether or not similar changes occur in the outer medullary collecting duct during chronic metabolic acidosis. Rats received ammonium chloride in their drinking water for 15 days and as a daily gavage for 3 days before sacrifice. Control rats received regular tap water. After collection of physiologic data the kidneys were fixed by in vivo perfusion with glutaraldehyde and processed for electron microscopy. No changes were observed in the principal cells. Morphometric analyses of the intercalated cells in both the outer and inner stripe revealed a significant increase in the surface density of the apical plasma membrane concomitant with a striking depletion of the tubulovesicular structures in the apical plasma region of the cell with chronic metabolic acidosis. These findings suggest that in response to chronic metabolic acidosis membrane, possibly containing a proton pump, is transported from the tubulovesicular membrane compartment to the apical plasma membrane of the intercalated cell.
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PMID:Response of intercalated cells of rat outer medullary collecting duct to chronic metabolic acidosis. 647 8


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