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)

It is widely accepted that in vivo the function of the papilla of the mammalian kidney is supported primarily by anaerobic metabolism. As a result, the major source of energy for support of function in the papilla is considered to be derived from glycolysis. This orientation originates from two concepts: 1) that in vivo the gaseous environment of the papilla has such a low PO2 that O2 availability limits O2 consumption, and 2) that papillary tissue has a high rate of glycolysis when compared with either cortical tissue or extrarenal tissues. It has also been tacitly assumed that papillary tissue has a "low" O2 uptake. Review of the measurements of PO2 of papillary tissue and of urine PO2 indicates that the PO2 of papillary tissue should not limit its aerobic mitochondrial oxidative metabolism. While the rate of aerobic glycolysis in papillary tissue is high, simultaneously papillary tissue has a rate of O2 uptake similar to that of liver and higher than that of muscle. The major (two-thirds) source of energy for papillary tissue in vitro is from O2 uptake. That papillary tissue is not exclusively dependent on glucose for its energy requirements is indicated by the greater stimulation of papillary tissue QO2 by succinate than by glucose. Thus, papillary tissue has both a high aerobic mitochondrial oxidative metabolism and a high aerobic glycolytic metabolism. It is suggested that the mechanism for the high rate of aerobic glycolysis in the presence of an adequate O2 supply is due to the relatively small mass of mitochondria in papillary tissue in relation to the amount of work done by the tissue. As a result of the limited rate of ATP production by the mitochondrial electron transport chain, the phosphorylation state ([ATP]/[ADP][Pi]) is reduced and the cytoplasmic redox state ([NAD+]/[NADH]) of the papillary collecting duct cells also becomes more reduced; changes in both ratios enhance the rate of glycolysis. This limited metabolic capacity of the collecting duct cells may permit an excess volume of solute and water to be excreted during volume expansion diuresis. The metabolic characteristics of the papilla, when compared to cortex, also provide a basis for the observed differences in substrate selectivity of cortex and medulla with respect to utilization of glucose and lactate. The experimental approaches that may provide information bearing on the suggested mechanisms for regulation of papillary metabolism in relation to tubular work functions are indicated.
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PMID:Is the function of the renal papilla coupled exclusively to an anaerobic pattern of metabolism? 22 Aug 81

The distribution and activities of several oxidative enzymes in the urinary apparatus of five freshwater fish species (river lamprey, lobe finned eel, Prussian carp, rainbow trout and three-spined stickleback) have been studied. Species were selected from three main taxonomic groups: Cyclostomata, Polypterini, Teleostei. Distinctly positive enzyme reactions were only found in the tubular elements of the kidney and the collecting duct-archinephric duct system, with the exception of the generally weak staining intensities of lactate dehydrogenase. The distal tubule normally showed strong to very strong reactions for most of the enzymes investigated. In the epithelial cells of the collecting tubule-collecting duct system, stronger reactions were observed for most of the mitochondrial-bound enzymes, especially succinate dehydrogenase and NADH-diaphorase. For these enzymes, the cells of the archinephric duct reacted strongly positive in Lampetra, Carassius and Gasterosteus. The enzyme patterns of various types of urinary tubules and ducts are compared with results of several morphological studies. In addition, the histochemical findings are discussed in relation to kidney function in different vertebrate groups.
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PMID:Oxidative enzymes in the urinary apparatus of several freshwater fishes. 43 99

Recently, we demonstrated that an ATPase stimulated by K (and not inhibited by ouabain, Na-K-ATPase inhibitor) is present in the connecting tubule (CNT) and collecting duct segments of the rabbit. In this study, we determined the effects of high- and low-K diet on K-ATPase activity in the CNT and collecting duct segments of rabbit. One group of animals was given a low-K diet (34 mEq/kg diet) and the other group was given a high-K diet (700 mEq/kg diet) for 1 week. K-ATPase activity was measured by a microfluorometric assay in which ATP hydrolysis is coupled to oxidation of NADH. Low-K animals had plasma K = 3.1 +/- 0.2 as compared with 5.5 +/- 0.5 mEq/l in high-K animals. Low-K animals had significant K-ATPase activity in CNT, CCD (cortical collecting duct) and MCD (medullary collecting duct). On the other hand, K-ATPase activity in all 3 segments from high-K animals was not significantly different from zero. These results support a hypothesis that chronic K loading suppresses the ouabain-insensitive K-ATPase in the distal nephron.
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PMID:Suppression of ouabain-insensitive K-ATPase activity in rabbit nephron segments during chronic hyperkalemia. 253 99

A plasma membrane ATPase sensitive to inhibition by N-ethylmaleimide (NEM) and insensitive to inhibition by oligomycin and ouabain has been shown to be involved in acidification of urine in the turtle bladder. The activity of this NEM-sensitive ATPase was determined in four types of distal nephron segments of normal rats and in rats treated with ammonium chloride. The enzyme activity was determined by a fluorometric micromethod in which ATP hydrolysis was coupled to NADH oxidation. Significant activities (10-35 pmol ADP X min-1 X mm-1) of NEM-sensitive ATPase were present in the distal convoluted tubule (DCT) and in the cortical and outer and inner medullary collecting duct segments of normal rats. In metabolic acidosis produced by ammonium chloride treatment (plasma CO2 content = 15.3 +/- 0.8 mequiv./L), the NEM-sensitive ATPase activity was increased significantly (60-100%) in the collecting duct segments without showing a significant change in the enzyme activity in the DCT. Our data are consistent with the hypothesis that a plasma membrane H+-ATPase (inhibited by NEM but not by oligomycin or ouabain) is involved in H+ secretion in the mammalian collecting duct.
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PMID:Stimulation of an N-ethylmaleimide-sensitive ATPase in the collecting duct segments of the rat nephron by metabolic acidosis. 293 19

An electrogenic H-ATpase sensitive to inhibition by N-ethyl-maleimide has been reported to be present in renal distal tubules. In contrast to another H-ATPase (gastric H-K-ATPase), the renal enzyme is not stimulated by K+ and is not inhibited by vanadate. However, our preliminary observations indicated that a K-stimulated ATPase (K-ATPase) sensitive to inhibition by vanadate is present in renal medullary collecting duct (MCD). To localize and further characterize this renal tubular K-ATPase, we measured K-ATPase activity in eight specific segments of the rabbit nephron. K-ATPase activity was the difference in ATPase activity in the presence and absence of KCl but in the presence of ouabain (to inhibit Na-K-ATPase). ATPase activity was determined by a fluorometric microassay in which ATP hydrolysis is coupled to the oxidation of NADH. There was a significant K-ATPase activity (expressed as pmol.min-1.mm-1) in the connecting tubule (CNT, 17.0 +/- 3.3), cortical collecting duct (CCD, 6.6 +/- 0.7), and MCD (8.8 +/- 1.7), but not in the proximal segments and the thick ascending limbs. The renal tubular K-ATPase was not only inhibited by vanadate but also by omeprazole and SCH 28080 (relatively specific inhibitors of gastric H-K-ATPase). It is concluded that K-ATPase present in the CNT, CCD, and MCD has some properties in common with gastric H-K-ATPase. However, the physiological role of K-ATPase in the distal nephron segments remains to be elucidated.
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PMID:Ouabain-insensitive K-adenosine triphosphatase in distal nephron segments of the rabbit. 296 63

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

The early effects of lithium on the kidney were studied in rats receiving a moderate daily dose (serum-Li: 0.5 to 0.8 mM per liter) for 3, 7, and 21 days. Enzyme histochemical reactions for acid and alkaline phosphatase, glucose 6-phosphatase, succinate and alpha-glycerophosphate dehydrogenase, and NADH tetrazolium reductase revealed changes confined to distal convoluted tubules and collecting ducts. The distal convoluted were unchanged at 3 days of treatment. At 7 days, a decrease in succinate dehydrogenase and NADH tetrazolium reductase and an increase in alpha-glycerophosphate dehydrogenase were noted. These changes were more conspicuous at 21 days and accompanied by tubular dilation and changes in light microscopic cellular morphology. In the collecting ducts, a cell enlargement and an increase in mitochondrial oxidative enzyme activities began to appear at 3 days, becoming more pronounced at 7 and particularly at 21 days. At 7 and even more at 21 days, a cellular hyperplasia was evident in the collecting ducts, and autoradiography after 3H-thymidine incorporation showed a marked increase in DNA synthesis in the collecting duct cells. The changes observed in the collecting ducts were most pronounced near the limit between the outer and the inner zone of the medulla. In conclusion, the rats developed morphologic changes at 3 to 7 days of treatment. The changes include (1) signs of cellular damage in the distal convoluted tubules and (2) hyperplasia and signs of increased functional activity in the collecting ducts.
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PMID:Early changes in renal distal convoluted tubules and collecting ducts of lithium-treated rats: light microscopy, enzyme histochemistry, and 3H-thymidine autoradiography. 706 26

11 beta-Hydroxysteroid dehydrogenase has been proposed to play an important role in aldosterone target cells by degrading endogenous glucocorticoids, thus allowing aldosterone to bind to the relatively nonselective mineralocorticoid receptor. The physiologically important species of this enzyme in renal aldosterone target cells appears to be kinetically and antigenically distinct from the previously characterized liver enzyme. Here we show that 11 beta-steroid dehydrogenase in the microsomal fraction of isolated renal collecting duct cells has a Km for corticosterone of 25.9 +/- 2.4 nM, about 100 times lower than the rat liver enzyme. Surprisingly, the collecting duct enzyme utilizes almost exclusively NAD as cofactor versus NADP used by the liver form. Conversion of corticosterone to 11-dehydrocorticosterone is 2.6 +/- 0.5 and 0.07 +/- 0.01 fmol/min/mg protein with 100 microM of NAD and NADP, respectively, demonstrating a 37.4 +/- 3.5-fold preference for NAD versus NADP. There is practically no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH, indicating that in collecting duct cells the enzyme operates only in the direction of oxygenation. In addition, 11 beta-steroid dehydrogenase activity is dose dependently inhibited by the end product 11-dehydrocorticosterone while the liver enzyme does not show end product inhibition. We conclude that renal collecting duct cells, the major physiological targets of aldosterone, are protected from circulating glucocorticoids by a hitherto undescribed enzyme of the 11-dehydrogenase family, which differs from the known liver enzyme in having a significantly higher affinity for corticosterone and a different cofactor requirement.
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PMID:A new isoform of 11 beta-hydroxysteroid dehydrogenase in aldosterone target cells. 849 39

Raising osmolality to 700 mosmol/kgH(2)O by the addition of NaCl rapidly kills most murine inner renal medullary collecting duct cells (mIMCD3), but they survive at 500 mosmol/kgH(2)O. At 300 and 500 mosmol/kgH(2)O, NADH autofluorescence is present in a mitochondria-associated, punctate perinuclear pattern. Within 45 s to 30 min at 700 mosmol/kgH(2)O, the autofluorescence spreads diffusely throughout the cell. This correlates with mitochondrial membrane depolarization, measured as decreased tetramethylrhodamine methyl ester perchlorate (TMRM) fluorescence. Mitochondrial dysfunction should increase the cellular ADP/ATP ratio. In agreement, this ratio increases within 1-6 h. Mitochondrial morphology (transmission electron microscopy) is unaffected, but nuclear hypercondensation becomes evident. Progressive apoptosis occurs beginning 1 h after osmolality is raised to 700, but not to 500, mosmol/kgH(2)O. General caspase activity and caspase-9 activity increase only after 6 h at 700 mosmol/kgH(2)O. The mitochondrial Bcl-2/Bax ratio decreases within 1-3 h, but no cytochrome c release is evident. The mitochondria contain little p53 at any osmolality. Adding urea to 700 mosmol/kgH(2)O does not change NADH or TMRM fluorescence. We conclude that extreme acute hypertonicity causes a mitochondrial dysfunction involved in the initiation of apoptosis.
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PMID:Mitochondrial dysfunction is an early event in high-NaCl-induced apoptosis of mIMCD3 cells. 1199 14