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)

This review summarizes the evidence for the defect in Na+-K+ pump in chronic renal failure, considers the role of various factors in causing this defect, and discusses the clinical implications thereof. Intracellular Na is elevated in erythrocytes, leukocytes, and muscle cells from some patients with chronic renal failure (CRF). Recent evidence suggests that this elevation of cell Na may be, in large part, a consequence of decreased number of Na+-K+ pump units per cell. Maintenance dialysis over a period of weeks ameliorates the defect in intracellular Na+, and this improvement is contemporaneous with an increase in the number of Na+-K+ pump sites per cell. In erythrocytes with normal cell Na+, acute hemodialysis increases the rate of Na+ and K+ transport. Many factors such as the presence of retained toxic metabolite or circulating inhibitor in the uremic plasma, or biochemical changes produced by acute hemodialysis, may explain this finding. In cells with high cell Na+, the pump-mediated K+ transport is normalized at the expense of a raised cell Na+. The decreased muscle membrane potential in uremic subjects has been attributed to a decreased activity of Na+-K+ pump. Enzymatic Na+-K+-ATPase activity of the uremic erythrocyte, leukocyte, sarcolemma, and intestines is also decreased. We discuss the role of hormonal abnormalities and circulating inhibitors, which may cause an acute inhibition of the pump and of other factors such as K+ depletion, which may cause more chronic alterations. The implications of alteration of Na+ and K+ pump transport and raised cell Na+ on other non-pump-mediated transport pathways are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Na+-K+ pump in chronic renal failure. 243 5

Ion pumping by the erythrocyte Na, K-ATPase has been measured using ouabain-sensitive 86Rb flux in 11 non-dialysed patients with chronic renal failure (CRF), 13 patients on haemodialysis (HD), 13 patients on peritoneal dialysis (CAPD) and 15 patients with functional transplants (FT). Flux measurements were performed in plasma and simultaneous estimates of specific 3H-ouabain binding were made. The results indicate that, compared to normal controls, Na,K pump flux was reduced by 21% in CRF (p less than 0.01), 30% in HD (p less than 0.01), 15% in CAPD (p less than 0.02), and was normal in FT. Mean specific ouabain binding sites per cell (+/- SEM) were; controls 366 +/- 16; CRF, 290 +/- 16; HD, 344 +/- 17; CAPD, 321 +/- 18; FT, 345 +/- 26. Calculation of mean turnover rate per pump site indicated that patients on HD showed a 30% reduction compared to controls (influx 55 K ions/s versus 79 K ions/s, p less than 0.01). Cross-incubation experiments suggest that the lowered pump flux seen in the CRF and HD groups was due to plasma factors. This work shows that erythrocyte Na,K pump number is reduced in CRF, while patients on maintenance HD have normal pump numbers per erythrocyte but reduced pump turnover.
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PMID:Effects of dialysis and transplantation on red cell Na pump function in renal failure. 255 64

Abnormalities in the function of the central nervous system exist in chronic renal failure (CRF) and some of these derangements may be related to excess parathyroid hormone (PTH) which causes a rise in brain calcium. The latter may affect metabolism of neurotransmitters such as norepinephrine (NE) in brain synaptosomes. We measured NE content, uptake and release in brain synaptosomes of CRF rats and studied whether excess PTH affects these parameters. Synaptosomes from rats with 21 days of CRF compared to those from normal animals have higher calcium content (11.4 +/- 0.92 vs. 7.1 +/- 0.50 nmol/mg protein, P less than 0.01) and lower Na-K ATPase activity (6.5 +/- 0.81 vs. 11.4 +/- 0.76 mumol Pi/mg protein/hr, P less than 0.01). NE content (11.0 +/- 0.60 vs. 13.6 +/- 0.55 pmol/mg protein/hr, P less than 0.01), uptake (46 +/- 4.5 vs. 110 +/- 5.9 pmol/mg protein times 50 min, P less than 0.01) and release (2.0 +/- 0.2 vs. 5.1 +/- 0.47 pmol/mg protein times 10 min, P less than 0.01). Parathyroidectomy (PTX) in CRF rats kept normocalcemic reversed these abnormalities in brain synaptosomes; indeed calcium content, Na-K ATPase activity and NE content, uptake and release in synaptosomes from PTX-CRF rats were not different from those seen in normal rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Abnormal norepinephrine uptake and release in brain synaptosomes in chronic renal failure. 255 7

Loss of lean body mass occurs frequently in patients with acute or chronic renal failure, but the mechanism(s) causing this abnormality are unknown. Using animal models of experimental uremia, it was found that excess lactate formation in muscle is directly related to the rate of protein breakdown. This suggests that abnormal energy metabolism may be one mechanism for protein wasting. A second mechanism involves metabolic acidosis. Metabolic acidosis activates the catabolism of protein and amino acids in muscle of uremic rats independently of azotemia. Defects in sodium transport by Na,K-ATPase and the Na/K/Cl cotransport system suggest that intracellular ions including hydrogen may be abnormal. If this were the case, uremia would increase the susceptibility to the catabolic effect of metabolic acidosis.
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PMID:Protein and amino acid metabolism in uremia: influence of metabolic acidosis. 263 59

Recent findings on endothelin, an endothelium-derived vasoconstrictor substance and endogenous digitalislike Na+, K+-ATPase inhibitor (s) obtained from animal and clinical experiments are reviewed. Endothelin is one of the most potent vasoconstrictive substances ever found; the pressor responses last for more than one hour after the bolus injection in rats. Because the pressor responses have not been attenuated by any known receptor-antagonists, the vasoconstriction is mediated by the endothelin receptors. Since messenger RNA for endothelin increases with thrombin, it may be involved in the damages of blood vessels. Radioimmunoassay for endothelin revealed that immunoreactive endothelin is increased in plasma of patients with chronic renal failure. Therefore, the plasma level of endothelin can be an index for some circulatory disorders. Since the Na+, K+-ATPase inhibitor cross-reacts with antidigoxin and antiouabain antibody, it is called a digitalis-like substance. We have demonstrated that cells containing the immunoreactive-substance to antidigoxin and antiouabain antibodies are restricted in the paraventricular and supraoptic nucleus of the hypothalamus, and that the plasma digoxinlike immunoreactivity increases with intracerebroventricular and intravenous infusions of hypertonic saline in rats. Because plasma concentrations of the immunoreactive substance significantly correlate with blood pressure, the substance seems to be involved in hypertension associated with excess intake of sodium salt.
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PMID:[Endothelin and endogenous digitalis-like substance in cardiovascular regulation: a review]. 268 97

The possibility that endogenous inhibitors of the sodium pump exist and bind to the cardiac glycoside binding site on Na+,K+-adenosine triphosphatase (ATPase) has been a source of much controversy. Although numerous hormones and inorganic ions that modulate Na+,K+-ATPase activity have been described, most of these affect the sodium pump indirectly by varying the intracellular sodium concentration or by increasing the number of enzyme units. None of these endogenous compounds has been shown conclusively to modulate sodium pump activity by binding to the cardiac glycoside binding site on Na+,K+-ATPase. However, the near-universal presence of three high-affinity binding sites on the alpha-subunit of the enzyme has engendered much speculation that endogenous ligands for these receptors must exist. In addition, none of the hormones known to indirectly affect sodium pump activity in vivo has been shown to modulate Na+,K+-ATPase activity in response to extracellular volume expansion or to play a role in the pathogenesis of hypertension or chronic renal failure, conditions in which a circulating inhibitor of Na+,K+-ATPase has been implicated. This report presents a condensed history of the search for endogenous inhibitors of Na+,K+-ATPase and describes recent advances in the field. Despite progress in identifying and characterizing compounds that could affect Na+,K+-ATPase activity in vivo, definitive proof for the existence of endogenous ligands for the cardiac glycoside binding site remains elusive.
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PMID:Endogenous cardiac glycosidelike compounds. 282 72

The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in [3H]ouabain binding, while in muscle, [3H]ouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia.
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PMID:Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats. 283 46

New method for measuring plasma and urinary Na-K-ATPase inhibitor (ATPI) was developed. Plasma and urine were extracted with reversed phase cartridge column and sample was reconstituted by assay buffer. Na-K-ATPase inhibitory activity of sample was monitored by continuously recording the absorbance of NADH at 340 nm, which coupled to the dephosphorylation of ATP. Ouabain was used for standards of Na-K-ATPase inhibition and this standard showed good linearity ranged 5-100 nmol/ml. Using this new method, P-ATPI and U-ATPI were quantitatively evaluated and paradoxical Na-K-ATPase stimulating phenomenon which observed in conventional method (Hamlyn et al) was diminished. Adopting of this new method for measuring plasma(P-) and urinary(U-)ATPI, and radioimmunoassay for P- and U-digitalis-like substance(DLS)--using crossreactivity to anti digoxin antibody--, these substances were estimated in patients with essential hypertension (EHT), chronic heart failure(CHF), primary and idiopathic hyperaldosteronism(HA), hyperthyroidism(BA) and chronic renal failure(CRF). In EHT, U-DLS, P-DLS, U-ATPI, P-ATPI were significantly higher than those of control(C). In CHF and BA, U-DLS and -ATPI were also significantly higher than those of C. In HA, U-ATPI, DLS distributed in wide range, and a few patients showed high levels of U-DLS and -ATPI. In CRF, P-DLS and -ATPI levels were significantly higher than those of C in prehemodialytic state but P-ATPI was significantly decreased after hemodialysis. From these results it is suggested that 1) DLS and ATPI might contribute to the etiology of hypertension. 2) Volume expansion stimulates the secretion of DLS and ATPI. 3) Stimulatory effect of volume expansion and inhibitory effect of mineralocorticoid may be responsible for wide distribution of these factors in HA. 4) DLS and ATPI are not the same substances.
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PMID:[Endogenous digitalis-like substance and Na-K-ATPase inhibitor in cardiovascular and renal disease]. 283 14

A number of erythrocyte Na-K ATPase units were measured in 22 patients with hyperthyroid Graves' disease, 3 with primary hypothyroidism, 3 with simple obesity, 13 with chronic renal failure on hemodialysis, and 20 normal controls, using ouabain binding assay as described by DeLuise et al. The number of Na-K ATPase units, derived by maximal binding of 3H-ouabain, was decreased in patients with simple obesity (Mean +/- SD, 0.26 +/- 0.07 pmol/10(9) RBC), as compared with that in normal controls (0.39 +/- 0.10), and a significant negative correlation between the number of the binding sites and the ratio of the measured body weight to the optimal body weight calculated by the modified Broca's method was observed in normal controls and patients with obesity (r = -0.51, p less than 0.05). The results agreed closely with that reported by DeLuise et al and provided validation of our estimates of the erythrocyte Na-K pump units. The maximal 3H-ouabain binding was significantly diminished in patients with hyperthyroid Graves' disease (0.28 +/- 0.07) when compared with that in normal controls, while the bindings were significantly elevated in patients with hypothyroidism (0.91 +/- 0.26). These results were in disagreement with those previously reported by animal studies where Na-K ATPase was found to be stimulated by thyroid hormones. It might be possible to partly explain this discrepancy by the degradation of Na-K ATPase in erythrocytes in addition to the apparent differences between erythrocytes and the other tissues and by the length of time that the tissue was exposed to the action of the hormones. Therefore, erythrocyte from normal controls and patients with hyperthyroid Graves' disease were divided into low and high density portions by a discontinuous 'percoll' density gradient centrifugation, and the bindings of the erythrocytes in two portions were separately measured. The bindings of erythrocyte in the higher density portion, representing relatively old-aged erythrocyte, were diminished to 92 +/- 19% of the bindings of the original whole erythrocytes in normal controls. An even more marked reduction of the maximal bindings of 3H-ouabain in old-aged erythrocytes was observed in patients with hyperthyroid Graves' disease (72 +/- 26%). Moreover, this % reduction based on aging related significantly to serum T4 concentrations in those patients (r = 0.85, p less than 0.05). These findings suggest that the number of erythrocyte Na-K ATPase units may reflect the overall peripheral metabolic state, regulated by thyroid hormone-dependent thermogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Clinical studies on assay for Na-K ATPase in human blood cells. I. Erythrocyte Na-K ATPase assay in patients with thyroid dysfunction and in those with chronic renal failure]. 284 3

To elucidate further the possible role of atrial natriuretic peptide (ANP) and hypothetical natriuretic hormone (NH) in volume and BP regulation in chronic renal failure (CRF) we measured plasma ANP, digitalis-like substances (DLS) and Na+-K+-ATPase activity (using 86Rb influx into RBC) in 9 patients with CRF before and after hemodialysis. Volume expansion between consecutive dialyses led in all patients to the elevation of plasma ANP (83.4 +/- 14.2 pmol/l) reaching in some overhydrated subjects and/or patients with concomitant cardiac insufficiency concentration greater than 150 pmol/l. Reduced 86Rb influx into RBC before hemodialysis (37.7 +/- 4.9% of controls) was accompanied by higher DLS concentrations (201 +/- 32 pmol/l). Ultrafiltration during hemodialysis with ECFV reduction lowered both ANP and DLS concentrations to 28.1 +/- 9.4 pmol/l and to 151 +/- 23 pmol/l, respectively, and abolished partly the inhibition of Na+-K+-ATPase activity (64.9 +/- 7.6% of controls). These changes corresponded to the degree of ECFV alteration. Our results suggest that both natriuretic principles are activated during ECFV expansion in CRF, probably as a corrective mechanism, with a tendency to normalize when ECFV is reduced during hemodialysis.
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PMID:Atrial natriuretic peptide concentration and natriuretic hormone activity in plasma of patients with chronic renal failure. 285 Sep 86


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