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)

Renal hydrogen ion excretion increases with chronic acid loads and decreases with alkali loads. We examined the mechanism of adaptation by analyzing vacuolar proton-translocating adenosine triphosphatase (H+ ATPase) 31-kD subunit protein and mRNA levels, and immunocytochemical distribution in kidneys from rats subjected to acid or alkali loads for 1, 3, 5, 7, and 14 d. Acid- and alkali-loaded rats exhibited adaptive responses in acid excretion, but showed no significant changes in H+ ATPase protein or mRNA levels in either cortex or medulla. In contrast, there were profound adaptive changes in the immunocytochemical distribution of H+ ATPase in collecting duct intercalated cells. In the medulla, H+ ATPase staining in acid-loaded rats shifted from cytoplasmic vesicles to plasma membrane, whereas in alkali-loaded rats, cytoplasmic vesicle staining was enhanced, and staining of plasma membrane disappeared. In the cortical collecting tubule, acid loading increased the number of intercalated cells showing enhanced apical H+ ATPase staining and decreased the number of cells with basolateral or poorly polarized apical staining. The results indicate that both medulla and cortex participate in the adaptive response to acid and alkali loading by changing the steady-state distribution of H+ ATPase, employing mechanisms that do not necessitate postulating interconversion of intercalated cells with opposing polarities.
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PMID:Expression and distribution of renal vacuolar proton-translocating adenosine triphosphatase in response to chronic acid and alkali loads in the rat. 182 94

Hydrogen ion secretion in the kidney is thought to be mediated in part by an N-ethylmaleimide (NEM)-sensitive proton-translocating adenosine triphosphatase (ATPase). This enzyme has been found throughout the nephron, but it has not been completely characterized enzymatically in the rat collecting duct. In the present study we characterized the NEM-sensitive ATPase from microdissected cortical (CCT) and medullary (MCT) collecting tubules of the rat nephron. At optimum conditions, NEM-sensitive ATPase activity was the same in both tubule segments: activity was 275.6 +/- 18.6 pmol/mm/h in the CCT and 280.3 +/- 35.2 pmol/mm/h in the MCT (n = 23, NS). ATP sensitivity was greater in CCT than in MCT, and in the former guanosine triphosphate was able to partially support enzyme activity. Maximal enzyme inhibition with NEM occurred at a lower concentration in CCT as compared to MCT. At pH 7.0 in MCT enzyme activity was approximately one half that seen at pH 7.4; in MCT and CCT, the pH optimum was 7.4. The temperature optimum in both segments was between 37 and 42 degrees C. Enzyme activity in CCT and MCT was linear to 30 min and proportional to tubule length. These results demonstrate that there are important differences in the NEM-sensitive ATPase isolated from two segments of rat collecting duct, and raise the possibility that enzyme heterogeneity may exist.
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PMID:Characterization of the N-ethylmaleimide-sensitive ATPase in rat cortical and medullary collecting tubule. 184 Feb 79

We examined the hypothesis that proton-potassium-activated adenosine triphosphatase (H-K-ATPase) mediates K absorption and acidification in the inner stripe of the outer medullary collecting duct (OMCDi). Rabbits were fed a low-K diet (0.55% K) for 7-14 d because we have demonstrated previously that this low-K diet stimulates K-absorptive flux by the OMCDi. Proton secretion was measured as net total CO2 flux (JTCO2) by microcalorimetry. After basal collections, either vehicle or an inhibitor of gastric H-K-ATPase, omeprazole (0.1 mM), was added to the perfusate during the second period. Addition of vehicle to the perfusate changed neither the transepithelial voltage (VT, in millivolts) nor the JTCO2. In contrast, the addition of omeprazole (0.1 mM) to the perfusate abolished JTCO2 (from 14.5 +/- 5.6 to -0.1 +/- 3.1 pmol.mm-1.min-1) without significantly affecting VT. In additional experiments, in 16 tubules there was significant net K absorption (JK) of 5.0 +/- 1.0 pmol.mm-1.min-1 during the basal period, which exceeded the rate of K absorption that could be attributed to a paracellular voltage-mediated pathway (JKP = 1.0 +/- 0.4 pmol.mm-1.min-1, P less than 0.01). Administration of vehicle did not significantly affect either VT or JK. However, omeprazole abolished JK (from 5.1 +/- 1.0 to 0.1 +/- 2.5 pmol.mm-1.min-1) without affecting VT or JNa. The present results demonstrate that the OMCDi possesses an active, omeprazole-sensitive acidification and K-absorptive mechanism. These findings are consistent with the presence of H-K-ATPase activity in this nephron segment.
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PMID:Active proton secretion and potassium absorption in the rabbit outer medullary collecting duct. Functional evidence for proton-potassium-activated adenosine triphosphatase. 254 29

Potassium secretion and sodium-potassium adenosine triphosphatase (Na-K-ATPase) activity in the distal nephron segments are known to be influenced by the dietary intake of K+. This has been attributed to a change in the plasma aldosterone level, which also influences K+ secretion and Na-K-ATPase activity in the distal nephron. To investigate whether or not dietary K+ can modulate Na-K-ATPase activity in the distal nephron independently of aldosterone, we determined Na-K-ATPase activity in four distinct nephron segments of adrenalectomized (adx) rabbits given four specific diets for 1 wk before experimentation. Na-K-ATPase activity was determined by a fluorometric microassay in which ATP hydrolysis is coupled to NADH oxidation. The nephron segments examined were the distal convoluted tubule (DCT), the connecting tubule (CNT), the cortical collecting duct (CCD), and the outer medullary collecting duct (MCD). All diets were similar in composition except for their K+ contents, which were 100, 300, 500, and 700 meq/kg in groups 1-4, respectively. In these adx animals, Na-K-ATPase activity increased greater than 200% in the CCD as the dietary intake of K+ increased. There was a linear relationship between K+ excretion and the enzyme activity in this segment. There was a 50% increase in Na-K-ATPase activity in the CNT as the dietary intake of K+ increased in adx animals. However, there were no significant differences in Na-K-ATPase activities in the DCT and MCD among the four treatment groups. It is concluded that dietary K+ intake can influence Na-K-ATPase activity in the CCD and CNT independently of plasma aldosterone levels.
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PMID:Renal adaptation to potassium in the adrenalectomized rabbit. Role of distal tubular sodium-potassium adenosine triphosphatase. 299 42

1. In order to explain the vulnerability of medullary thick ascending limb of Henle's loop (mTAL) during hypoxia, adenosine 5'-triphosphate (ATP) content was measured in isolated rat mTAL cells during control conditions and chemically induced hypoxia and compared with those in medullary collecting duct (MCD) cells. 2. Basal ATP levels in mTAL and MCD were estimated as 3.6 and 2.1 mmol/l, respectively. Antimycin A (5 mumol/l) decreased the ATP content by 41% of the control value in the mTAL cells, but failed to reduce that of the MCD cells. Administration of sodium cyanide (5 mmol/l) drastically depleted ATP in the mTAL cells within 5 min (2-3% of control). On the other hand, ATP levels in MCD cells were sustained for at least 60 min after cyanide administration (64% of control). 3. When tubules were made permeable to sodium by the addition of nystatin, the effects of chemical hypoxia on the cell ATP levels were intensified in both segments, and this was partially blocked by pretreatment with ouabain, or by lowering the sodium concentration of the medium. 4. Higher doses of nystatin in mTAL caused a reduction in ATP levels even under control conditions, but its effect was prevented in low sodium medium. 5. The present study suggests that cell ATP levels can be altered by sodium, potassium-dependent adenosine triphosphatase activity, and that due to their high sodium-transporting activity, mTAL cells are more sensitive to reductions in ATP levels during hypoxia than are MCD cells.
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PMID:A bioenergetic explanation for the selective vulnerability of renal medullary tubules to hypoxia. 341 64

Enzymatic and microperfusion studies have indicated that an ATP-dependent H+/K+ exchange process is present in the collecting duct of the mammalian kidney. Immunochemical staining has also provided evidence for expression of a gastric-type H(+)-K+ adenosine triphosphatase (H(+)-K(+)-ATPase). Rat kidney mRNA was probed with use of the polymerase chain reaction (PCR) to determine the presence of an H(+)-K(+)-ATPase. cDNA made with mRNA isolated from the kidneys of rats maintained on a low-K diet was used as template in PCR reactions with primers encompassing the cDNA sequence of the alpha-subunit of the gastric H(+)-K(+)-ATPase and the 5' and 3' ends of the colonic H(+)-K(+)-ATPase. The resulting products, 300-700 bp in size, hybridized with probes directed against either the gastric or colonic sequences of the H(+)-K(+)-ATPase. Sequencing of the individual PCR products showed identity with the appropriate regions of the alpha-subunits of the gastric H(+)-K(+)-ATPase and colonic H(+)-K(+)-ATPase. These data indicate that the rat kidney expresses mRNAs encoding both gastric and colonic H(+)-K(+)-ATPases.
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PMID:Expression of gastric and colonic H(+)-K(+)-ATPase in the rat kidney. 773 14

Acidosis increases and alkalosis decreases proton secretion in the inner medullary collecting duct (IMCD). We examined the mechanism of this adaptation by studying the immunocytochemical distribution of the vacuolar H-adenosine triphosphatase (ATPase) in the IMCD from rats subjected to acid or alkali loads for a mean duration of 4 and 9 days. For immunocytochemical staining, a monoclonal antibody to the 31-kD subunit of the bovine kidney vacuolar H-ATPase was used. Intercalated cells were present only in the initial IMCD, and the principal cells and IMCD cells showed no appreciable H-ATPase staining under any experimental conditions. We found significant adaptive changes in the distribution of H-ATPase in the intercalated cells of the IMCD. H-ATPase staining in acid-loaded rats shifted from cytoplasmic vesicles to apical plasma membrane, whereas in alkali-loaded rats cytoplasmic vesicular staining was enhanced and staining of plasma membrane disappeared. These adaptive changes were most prominent on day 4 of acid-loaded and days 4 and 9 of alkali-loaded rats. Our results indicate that translocation of the H-ATPase pump between cytoplasmic vesicles and apical plasma membrane of the intercalated cells is an important mechanism is adaptation of the IMCD to chronic acid base perturbations.
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PMID:Adaptation of inner medullary collecting duct vacuolar H-adenosine triphosphatase to chronic acid or alkali loads in the rat. 792 69

Interleukin-1 (IL-1) causes a diuresis and natriuresis in experimental animals. The natriuresis is due, at least in part, to IL-1 stimulation of prostaglandin E2 (PGE2) synthesis by the inner medullary collecting duct (IMCD), with resultant inhibition of Na(+)-K(+)-adenosine triphosphatase activity. It is unknown whether IL-1 affects other signal transduction systems in the IMCDs that regulate nephron sodium and water reabsorption. Furthermore, indirect evidence suggests that IL-1 inhibits sodium and water transport in other nephron segments. Consequently we examined (1) the effect of IL-1 on cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation by rat IMCD cells and (2) IL-1 stimulation of signal transduction mechanisms throughout the nephron. IL-1 had no affect on cGMP or arginine vasopressin-dependent (AVP-dependent) or isoproterenol-dependent cAMP accumulation in cultured rat IMCD cells. IL-1 increased PGE2 levels in rabbit IMCD, cortical collecting tubule (CCT), and to a lesser extent, medullary thick ascending limb cells, but had no effect on proximal tubule cells. IL-1 also did not alter AVP-dependent cAMP accumulation in the CCT. The failure of IL-1 to reduce AVP responsiveness in the CCT was not due to culture conditions, because AVP-dependent cAMP accumulation in freshly isolated CCT cells was also not affected by the cytokine but was inhibited by exogenous PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 regulation of collecting duct prostaglandin E2 and cyclic nucleotide accumulation. 819 73

The ultrastructure of renal tubule cells was studied in the European lesser spotted dogfish by the evaluation of thin sections and freeze fracture replicas. Computer-assisted three-dimensional reconstruction of entire nephrons was performed. The distinction of nephron segments and collecting tubule was made using results of previous histological work. The first proximal tubule segment (PI) consists of two subsequent portions, PIa and PIb. PIa is a component of the lateral countercurrent bundle, and PIb, which displays an apical tubulovesicular apparatus and an extended lysosomal compartment, is located in the vicinity of the glomeruli. Rod-shaped intramembrane particles were detected in PIa. The second proximal tubule segment (PII) is a special segment in elasmobranch and teleost fish. PII differs largely from PI in cell morphology and function. The apical cytoplasm was filled with small clear vesicles, and an apical endocytic apparatus was lacking. In the apical cell membrane, rod-shaped particles were revealed by freeze fracture. The apical tight junctions of PI and PII consisted of seven to ten meandering strands. The distal nephron was subdivided into two major segments: early distal tubule (EDT) in the lateral countercurrent bundles and late distal tubule (LDT) in the mesial tissue. The EDT showed marked amplification of basolateral cell membranes. The tight junctions displayed a low number of continuous parallel strands, which is also characteristically found in the diluting segments of other vertebrates. LDT cells showed cytoplasmic studs and rod-shaped intramembraneous particles at the apical cell membrane, thereby resembling type A intercalated cells of collecting duct. The collecting tubule (CT) emerged from the LDT and was part of the countercurrent arrangement inside the lateral bundles. Tight junctions of LDT and CT consisted of many meandering strands in a honeycomb pattern. With immunohistochemistry, binding sites of a polyclonal antibody against an extraplasmic portion of rat gastric H(+)-K(+)-adenosine triphosphatase (ATPase) were observed at the apical cell membrane of PIa, PII, and LDT. From the colocalization of binding sites for the antibody against the transport enzyme with rod-shaped intramembrane particles, we assume that these might be the morphological correlate of gastric H(+)-K(+)-ATPase-like enzyme in the renal tubule.
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PMID:Renal tubule of dogfish, Scyliorhinus caniculus: a comprehensive study of structure with emphasis on intramembrane particles and immunoreactivity for H(+)-K(+)-adenosine triphosphatase. 838 22

Multiple cyst formation with fluid retention is a characteristic structural abnormality in polycystic kidney disease (PKD). Na/K adenosine triphosphatase (ATPase) is a major transporting membrane protein that is ubiquitous in the epithelial cell, which has been thought to be involved in cystogenesis. We have investigated the molecular and histologic basis of Na/K ATPase activity in experimental PKD in vivo. Rats were treated with diphenylthiazole (100 mg/100 gm body weight), and cyst formation was examined histologically. Na/K ATPase activity was measured enzymatically by using a fluorometric method, and reverse transcription-competitive polymerase chain reaction (RT-PCR) analysis was used to quantitate mRNA levels in the isolated single nephron segment. Kidneys were immunostained with subunit-specific antibodies to determine the localization of Na/K ATPase in the epithelial cell. The enzyme activity increased in the cortical collecting duct from 25.9 +/- 3.5 mmol/Lpmol/mm/min to 72.9 +/- 6.8 pmol/mm/min and in the outer medullary collecting duct from 13.0 +/- 3.9 mmol/Lpmol/mm/min to 58.5 +/- 9.8 pmol/mm/min (n = 6, p < 0.01); however, all other segments showed no significant changes. No significant alternation in alpha 1- and beta 1-subunits of Na/K ATPase mRNA levels was observed by competitive PCR assay in either segment. The enzyme was stained at the basolateral membrane even in the cystic tubules. Na/K ATPase activity was up-regulated in the cyst-formed kidney, but this was not accompanied with transcriptional up-regulation. Increased Na/K ATPase activity at normal locations may play a role in abnormal net fluid transport in the development and progression of experimental PKD.
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PMID:A role for Na/K adenosine triphosphatase in the pathogenesis of cyst formation in experimental polycystic kidney disease. 914 48


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