Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanisms determining the natriuresis in ECV expansion are not yet completely known. The present study was therefore performed to investigate (1) the extent to which prostaglandins (PG) are involved in the natriuresis of ECV expansion and (2) by which mechanisms PG may affect renal Na absorption. In nonexpanded rats the prostaglandin synthetase inhibitor indomethacin (INDO) had no effect on renal function. In 16 Sprague-Dawley rats EVC expansion with isotonic saline corresponding to an increase in body weight of 10% was induced and maintained for 60 min. Ten animals received an oral dose of 10 mg/kg BW of INDO prior to ECV expansion. Six animals served as controls (C). Blood pressure (INDO: 132 +/- 4 (SE); C: 130 +/- 3 mm Hg), GFR (INDO: 12.5 +/- 1.0; C: 10.5 +/- 0.9 ml/min/kg BW), fractional K excretion (INDO: 32.1 +/- 2.6; C: 43.4 +/- 4.8%), CH2O and Na-k-ATPase activities in renal cortex, medulla and papilla did not significantly differ in either group. Significant differences were observed in urinary flow rate (INDO: 0.82 +/- 0.8; C: 1.82 +/- 0.23 ml/min/kg KG) and fractional Na absorption (INDO: 91.9 +/- 1.1; C: 81.7 +/- 1.2%). The results indicate that PG are involved in the natriuresis following acute expansion of the ECV and suggest that PG may inhibit the intrinsic tubular capacity for Na absorption in the rat.
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PMID:The role of prostaglandins in the natriuresis of acutely salt-loaded rats. 85 79

To further characterize changes in tubular Na-K-ATPase in acute tubular necrosis (ATN), segmental analysis was performed in rat nephrons. Na-K-ATPase was assayed in the following segments: proximal convolution (PC), proximal straight (PS), outer medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), distal convolution (DC) and cortical collecting duct (CCD) in three groups of rats: 1.) intact; 2.) moderate non-oliguric ATN; and 3.) severe oliguric ATN. GFR and CNa/GFR X 100 were in group 1 0.80 +/- 0.05 ml/min and 0.68 +/- 0.06, in group 2 0.14 +/- 0.02 and 1.46 +/- 0.35, and in group 3 0.04 +/- 0.01 and 0.46 +/- 0.15, respectively. Na-K-ATPase in PC and PS were similar in all three groups. Na-K-ATPase levels were in MTAL: in group 1 37 +/- 2 X 10(-11) mol/mm/min, in group 2 20 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 24 +/- 2 X 10(-11), P less than 0.001 versus group 1. In CTAL Na-K-ATPase levels were: in group 1 40 +/- 2 X 10(-11), in group 2 33 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 27 +/- 2 X 10(-11), P less than 0.001 versus groups 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced Na-K-ATPase in distal nephron in glycerol-induced acute tubular necrosis. 215 4

The effect of suppression of prostaglandin synthesis on renal sodium handling and microsomal Na-K ATPase was studied in control and indomethacin treated intact rats maintained on a normal sodium diet (series A) and chronically salt loaded (series B). Indomethacin administration resulted in a decreased GFR and a significantly depressed urinary excretion and an increased fractional reabsorption of sodium in animals fed the normal sodium diet or chronically salt loaded. In rats maintained on a normal Na diet, the activity of the renal medullary Na-K ATPase after indomethacin was 206.3 +/- 6.4 ug Pi/mg protein, i.e. significantly higher as compared with the enzyme activity in the medullary renal fraction from control animals in which it averaged 148 +/- 7.79 ug Pi/mg protein (p less than 0.001). While after chronic salt load a similar increment in the activity of renal medullary Na-K ATPase was observed, no additional stimulation was elicited by subsequent indomethacin administration. The addition of exogenous PGE2, 0.1 mM to microsomal fractions obtained from kidneys of normal rats, was associated with a moderate suppression of the medullary Na-K-ATPase activity, from a basal level of 170 +/- 16 to 151.3 +/- 13 umol Pi/mg protein/hr (p less than 0.005). In isolated segments of medullary thick ascending limb of Henle's loop (MTAL) addition of PGE2 to the incubation medium resulted in a significant inhibition of Na-K ATPase from 37.2 +/- 2 to 21.25 +/- 1.17 x 10(-11) mol/mm/min (p less than 0.0001). These findings suggest that the increased renal Na reabsorption after inhibition of PG synthesis might be related, at least partly, to stimulation of medullary Na-K ATPase. In parallel, the reported natriuretic effect of prostaglandins might imply a direct inhibitory effect of these mediators on renal Na-K ATPase.
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PMID:Renal sodium handling and stimulation of medullary Na-K-ATPase during blockade of prostaglandin synthesis. 215 24

Although numerous studies have documented the effects of the renal nerves on kidney function, the mechanisms involved in the diuresis have yet to be elucidated. The present study was undertaken to examine the effect of acute unilateral renal denervation (DNX) on proximal tubular absorption of fluid and bicarbonate and to determine if acute DNX was associated with changes in Na-K-ATPase activity. Acute DNX caused significant increases in urine flow and absolute and fractional excretions of Na, HCO3 and K compared to the contralateral control kidney (INN) or sham denervated kidneys in normal rats as well as in rats made alkalotic by the I.V. infusion of 150 mM NaHCO3. These effects were seen without significant changes in GFR. When proximal convoluted tubules (PCT) were perfused with bicarbonate-Ringer's solution DNX resulted in a 67% decrease in fluid reabsorption (INN: 3.0 +/- 0.2 vs DNX: 1.0 +/- 0.1 nl/min/mm; p less than 0.001) and a 40% decline in bicarbonate (total CO2) reabsorption (INN: 151.3 +/- 8.8 vs DNX: 94.5 +/- 10.1 pmol/min/mm; p less than 0.01). Acute DNX caused a significant reduction in Na-K-ATPase activity measured in microsomes derived from the outer cortex of the kidney (INN: 13.2 +/- 1.3 vs DNX: 10.9 +/- 0.7 mumol PO4/mg prot/hr; p less than 0.01) while Mg-ATPase was unaffected. Sham denervation had no effect on any of the above parameters. These results indicate that the renal nerves play an important role in the regulation of bicarbonate and fluid reabsorption in the PCT. The diuresis, natriuresis, and bicarbonaturia associated with acute unilateral renal denervation may be the direct result of inhibition of Na-K-ATPase activity.
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PMID:Sodium and bicarbonate reabsorption in microperfused proximal tubules from the denervated rat kidney: relationship to cortical Na-K-ATPase activity. 217 83

Normal adults with normal protein intakes have a urinary NH4 excretion of 40 to 50 mmol/24 hours and a variable urinary pH. In cases of metabolic acidosis a urinary pH less than 5.5 suggests an extra-renal origin whilst a urinary pH greater than 5.5 is in favour of renal acidosis, but there are many exceptions to this rule. On the other hand, urinary NH4 excretion is always greater than 70 mmol/24 hours in the first case and less than 40-50 mmol/24 hours in the second; and the use of the urinary anionic gap (Na + K - Cl), negative in the first case and positive in the second, enables the two situations to be distinguished. The acidosis of nephron reduction is easily recognised in cases of severe renal failure with an increase in unmeasured plasma anions whilst tubular acidoses are accompanied by a hyperchloremia. Measurement of fractional HCO3 excretion after an oral loading dose of NaHCO3, preferably by TmCHO3 with respect to GFR, distinguishes proximal tubular acidosis (low TmHCO3) from distal tubular acidosis (normal or high TmHCO3). In the latter case, the presence of hypokalemia suggests a distal tubular acidosis either due to deficiency of the H(+)-ATPase pumps (absence of increased urinary pCO2 after oral loading dose of NaHCO3) or to the inability of the kidney to maintain a normal H+ gradient (normal increase of urinary pCO2. The presence of hyperkalemia suggests diseases associated with hypoaldosteronism (low or inappropriate serum aldosterone concentrations), abnormal transepithelial voltages or with a pseudo-hypoaldosteronism syndrome (high plasma aldosterone concentration). The prevalence of distal tubular acidosis with hyperkalemia is on the increase whilst tubular acidosis with hypokalemia remains rare.
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PMID:[Renal acidosis]. 223 3

Na-K-ATPase activity was studied in tubule segments from the cortex and medulla of rabbit kidneys under normal conditions, after unilateral nephrectomy, and after chronic salt loading. After unilateral nephrectomy kidney weight increased by 37% and Na-K-ATPase activity rose significantly in all nephron segments by 36-200% (P less than 0.01). Oral salt loading for 2 wk with 0.5% NaCl caused an increase in GFR and in absolute sodium excretion as well as reabsorption; plasma aldosterone decreased by 44% (P less than 0.005). In the proximal segments (PCT, CPST, OMPST, and TDL) there were no marked changes in Na-K-ATPase activity, whereas along the whole length of the ascending limb of Henle's loop (iMTAL, MTAL, and CTAL) there was a significant rise in the enzymatic activity of 30-200% (P less than 0.02). In the distal segments (DCT, CCD, and OMCD) there was a marked decrease of 50-60% (P less than 0.005) in Na-K-ATPase activity after the salt loading. We conclude that unilateral nephrectomy caused a general increase in Na-K-ATPase activity along the whole length of the nephron, and salt loading caused a selective increase in enzyme activity along the ascending limb of Henle's loop and decrease in the distal segments.
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PMID:Na-K-ATPase in isolated rabbit tubules after unilateral nephrectomy and Na+ loading. 298 46

In the mammalian kidney, the use of the ratio, delta net T-Na+/delta Q-O2, provides an overestimate of the energy requirements for unidirectional active Na+ transport. In the proximal tubule, the overestimate of the energy cost for T-Na+ is due to these phenomena: (1) The "leaky" characteristics of the proximal tubule does not permit an accurate estimate to be made of the active fraction of the unidirectional flux of Na+. Thus, the net Na+ or net HCO3- reabsorption rate alone cannot be used to determine the stoichiometry for unidirectional extrusion of Na+ (with HCO3-) by the Na,K-ATPase, since backflux of HCO3- into the lumen occurs. (2) There is a moiety of active Na+ with Cl- along the pars recta. Whether this reabsorptive rate is altered and O2 uptake also changed when GFR or NaHCO3 reabsorption is varied is not yet known. (3) The occurrence of energy-requiring synthetic functions (substrate-interconversions) in the proximal tubule, coupled, in part, to the rate of Na+ entry into the proximal tubule cells, results in changes in renal O2 uptake proportional to some (undetermined) fraction of the change in Na+ reabsorption. The utilization of a portion of these reabsorbed substrates in endergonic syntheses must account for a portion of the Na+-stimulated suprabasal O2 uptake rate. Hence, the presence of synthetic functions in the proximal tubule also contributes to the overestimation of the energy value of net Na+ reabsorption when the ratio, delta net TNa-+/delta Q-O2, is used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between energy requirements for Na+ reabsorption and other renal functions. 351 12

Renal tubular secretion of digoxin appears to be one of the main ports of elimination of the glycoside from the body. Because of its narrow therapeutic window and severe toxicity, the mechanisms of tubular handling of digoxin are important. Moreover, several drugs which are commonly administered with digoxin, including quinidine, spironolactone, verapamil and amiodarone have been shown to decrease renal clearance of digoxin without affecting GFR. We studied the handling of digoxin using in vitro and in vivo approaches. The handling of the glycoside by the brush border suggests passive reabsorption which is not enhanced by commonly coadministered drugs. Digoxin binding to the antiluminal (basal) membrane suggests that the secretion of the glycoside may not involve the pharmacologic receptor, the Na+, K+, ATPase. Using the multiple indicator dilution technique, we could directly show the two steps of secretion of digoxin: Its sequestration from the postglomerular circulation, and its appearance in the urine after transtubular transport. Digoxin transport is not inhibited by a cationic or anionic molecule (PAH and tolazoline). It is possible that digoxin is secreted by a yet unidentified transport mechanism.
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PMID:Cellular mechanisms of digoxin transport and toxic interactions in the kidney. 353 41

Renal sodium handling and microsomal Na+-K+-ATPase activity in kidney cortex, medulla and papilla of rats with streptozotocin-induced diabetes mellitus (DM) was studied. During 7 days following the administration of streptozotocin GFR, urinary excretion, filtered load and tubular reabsorption of Na+ averaged (mean +/- SE) 1.18 +/- 0.016 ml/min, 1.74 +/- 0.14, 177.3 +/- 8.9 and 175.6 +/- 8.9 mEq/min respectively in experimental rats as compared to corresponding rates of 0.85 +/- 0.04 (P less than 0.001), 0.85 +/- 0.03 (P less than 0.001), 129.8 +/- 5.8 (P less than 0.001) and 129 +/- 5.8 (P less than 0.001) respectively in the control rats. The activity of microsomal Na-K-ATPase in the kidney cortex, medulla and papilla of the control group was (mean +/- SE) 44.7 +/- 1.7, 150 +/- 7.5 and 37.4 +/- 3.6 (mumoles Pi/mg prot/h) respectively. 24 h after DM induction Na-K-ATPase activity in the cortex rose to 59.3 +/- 2.4 (P less than 0.001) and remained high after 3 and 7 days. Medullary Na-K-ATPase activity was unchanged 24 h after streptozotocin administration but was markedly increased to 260 +/- 9 (P less than 0.001) after 3 days and remained high after 7 days. These findings show that streptozotocin-induced DM in rats causes a substantial increase in GFR which is associated with a net increase in filtered and reabsorbed load of Na+ and natriuresis. These alterations are accompanied by a marked increase in Na-K-ATPase activity in renal medulla and in the cortex.
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PMID:The effect of streptozotocin-induced diabetes mellitus on urinary excretion of sodium and renal Na+-K+-ATPase activity. 608 93

The inhibition of renin secretion and the vasoconstrictive action of cardiac glycosides may be attributed to increases in cytosolic calcium as a result of inhibition of Na+-K+-ATPase. These studies examined in the dog in vivo the role of calcium on the renal actions of ouabain as assessed from the modifying effects of calcium channel blockers. Since vanadate, another Na+-K+-ATPase, inhibitor, enhances in vitro the binding of ouabain to Na+-K+-ATPase, we examined the capacity of vanadate to modify the renal effects of ouabain in vivo. Infusion of ouabain (1 microgram X kg-1 X min-1) into the renal artery decreased RBF, GFR, and renin secretion, and produced diuresis and natriuresis. When ouabain was infused in dogs receiving the calcium channel blocker verapamil (100 microgram/min), it failed to suppress renin secretion or cause renal vasoconstriction. In addition, verapamil produced diuresis and natriuresis, which were greatly enhanced by ouabain (e.g., verapamil FENa 12.0 +/- 1.1----34.2 +/- 5.1%). The data strongly suggest that calcium entry into cells is a major mediator of the renin inhibitory effect and of the renal vasoconstriction induced by cardiac glycosides. The natriuresis observed during the calcium channel blocker infusion suggests that this drug may have a direct tubular effect on sodium reabsorption. Superimposition of vanadate (0.5 mumol/min) on ouabain infusion led to massive natriuresis (FENa, 5 +/- 1----35 +/- 4%), renal vasodilation (RBF 90 +/- 12----170 +/- 15 ml/min), and an increase in renin secretion (delta, 100%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Na+-K+-ATPase inhibitors and renin release: relationship to calcium. 609 56


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