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)

In patients with chronic uremia we have previously demonstrated a significant inhibition of the Na-K-ATPase enzyme which represents the specific receptor protein for cardiac glycosides. Since an endogenous inhibitor of this enzyme was previously shown to react with a digoxin antibody, in the present study we determined digoxin-like immunoreacting activity(ies) (DLIA) by a radioimmunoassay in 15 nondialyzed patients with chronic renal failure. In native serum, DLIA ranged from 0 to 1.70 ng/ml and was unrelated to the degree of renal failure. After gel filtration of serum, DLIA exclusively eluted in the small molecular weight salt (FIII) and post-salt (FIV) fractions and averaged 0.22 +/- 0.04 and 0.20 +/- 0.05 ng/ml in fractions III and IV, respectively. Total activities ranged from 0.11 to 0.88 ng/ml with a mean of 0.42 +/- 0.06 ng/ml and closely correlated with the degree of renal impairment (p less than 0.001). The results confirm the presence of small molecular weight digoxin-like immunoreacting substance(s) in uremic serum. The variable activities in native serum and the lack of correlation between the degree of renal failure and DLIA in serum fraction IV previously shown to possess the Na-K-ATPase-inhibiting activity, however, indicate that DLIA may not reflect specifically the endogenous sodium pump inhibitor and that unspecific binding to this digoxin antibody of uremic toxins or other endogenous compounds, such as steroids other than aldosterone, may have occurred.
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PMID:Digoxin-like immunoreacting substance(s) in the serum of patients with chronic uremia. 401 Aug 43

We studied the erythrocyte Na,K-pump in chronically hemodialyzed uremic patients, immediately before and after a 4-h period of hemodialysis. Using [3H]ouabain as a probe, the number of Na,K-pump units per erythrocyte did not differ in uremic and control subjects, and hemodialysis had no acute effect on this parameter. In contrast, in these same cells the mean level of Na,K-pump-mediated 86Rb transport was 30% lower in predialysis uremic patients than in controls, and this diminution in the rate of 86Rb transport per pump unit was improved after 4 h of hemodialysis in 17 of 18 subjects. The results of in vitro incubation of normal cells with pre- and post-dialysis sera from uremic patients suggested that a serum factor is responsible for the observed inhibition of Na,K-pump activity. Changes in cell Na concentration during dialysis did not appear to be responsible for the increased rate of Na,K-pump turnover after hemodialysis. However, there was a significant correlation between the extent of rise in pump-mediated 86Rb uptake and the weight loss that occurred during dialysis. We conclude that the ion transport turnover rate of the erythrocyte Na,K-pump is impaired in uremia by a nonouabain like circulating factor. This factor, whose activity is diminished acutely by hemodialysis, may play an important role in the systemic manifestations of the uremic syndrome, and could be an important endogenous regulator of the Na,K-ATPase.
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PMID:Erythrocyte Na,K pump in uremia. Acute correction of a transport defect by hemodialysis. 608 16

When compared to that from sham-operated controls, sarcoplasmic reticulum isolated from skeletal muscle of uremic rabbits had a lower rate of calcium uptake and storing capacity. In vivo administration of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] restored the values in uremic animals toward normal. To obtain information about the mechanisms responsible for these differences, phosphorylation of the calcium transport ATPase was studied. The steady-state levels of phosphoprotein in uremic membranes were lower and returned to normal when the secosteroid was administered. Electrophoresis of the membranes phosphorylated with 32P-inosine triphosphate (32P-ITP) showed that the differences were related to a 100,000 dalton protein. The rate of phosphoprotein formation, determined with 32P-ITP and at 0 degrees C, was considerably lower in uremic than in control animals. Pretreatment with 1,25(OH)2D3 prevented this change. The hypothesis is advanced that the vitamin D metabolite affects the steady-state concentration and rate constant of formation of active sites in the Ca-ATPase. These results may partly explain the altered Ca transport function of the sarcoplasmic reticulum in experimental uremia.
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PMID:Reversal of decreased phosphorylation of sarcoplasmic reticulum calcium transport ATPase by 1,25-dihydroxycholecalciferol in experimental uremia. 622 86

The frequent occurrence of sensorineural hearing loss in patients with chronic renal insufficiency prompted us to study the influence of chronic renal failure upon Na+,K+-ATPase in the inner ear of guinea pigs. Na+,K+-activated ATPase was defined as the ouabain-sensitive part of total ATPase, the activity of which was obtained in the presence of sodium, potassium and magnesium. A significant reduction of Na+,K+-activated ATPase was found in the inner ear of uremic animals. Such inhibition could be demonstrated as early as 12 hours after subtotal nephrectomy. An inverse correlation was found between serum creatinine levels and Na+,K+-activated ATPase. A similar inhibition of Na+,K+-activated ATPase in uremia is also found in other tissues (erythrocytes, renal tubules, intestinal mucosal cells, sarcolemma). Na+,K+-ATPase in the cochlea plays a key role in the maintenance of cochlear cationic gradients. It is suggested that inhibition of this enzyme system may contribute to the inner ear dysfunction in uremia.
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PMID:Inhibition of Na+,K+-stimulated ATPase in the cochlea of the guinea pig. A potential cause of disturbed inner ear function in terminal renal failure. 625 27

The survival of erythrocytes (RBC) is shortened in uremia, and it has been shown that calcium influx into RBC evoked crenation and increased their rigidity. The high blood levels of parathyroid hormone (PTH) may augment entry of calcium into RBC and hence affect their integrity. We examined the effect of PTH on osmotic fragility of human RBC and investigated the mechanisms through which PTH interacts with RBC. Both the amino-terminal (1-34) PTH and the intact (1-84) PTH, but not the carboxy-terminal (53-84) PTH, produced significant increases in osmotic fragility. This effect was abolished by prior inactivation of the hormone. There was a dose-response relationship between both moieties of PTH and the increase in osmotic fragility. This action of PTH required calcium, was mimicked by calcium ionophore, and was partially blocked by verapamil. PTH caused significant influx of (45)Ca into RBC, which was not associated with potassium leak. The hormone did not affect water content of RBC. Scanning electron microscopy revealed that the incubation of RBC with PTH was associated with the appearance of membrane filamentous extensions, which anchor RBC together. Inhibition of glycolytic activity of RBC with NaF or inhibition of Na-K-activated ATPase with ouabain did not abolish the effect of PTH on osmotic fragility. PTH did not stimulate RBC Na-K-activated ATPase or Mg-dependent ATPase but caused marked and significant stimulation of Ca-activated ATPase. The basal activity of the RBC adenylate cyclase was low and PTH produced only a modest stimulation of this enzyme. Both cyclic AMP and dibutyryl cyclic AMP had no effect on osmotic fragility. THE DATA INDICATE THAT: (a) the RBC is a target organ for PTH, (b) the hormone increases osmotic fragility of RBC, and (c) this effect of PTH is due to enhanced calcium entry into RBC. We suggest that the increased calcium influx may affect the spectrin-actin of the cytoskeletal network of the RBC and may alter the stability and integrity of the cell membrane. This action of PTH on the RBC could be, at least in part, responsible for the shortened survival of RBC in uremia, and assign a new role for PTH in the pathogenesis of the anemia of uremia.
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PMID:Effect of parathyroid hormone on osmotic fragility of human erythrocytes. 628 9

Red blood cell (RBC) phosphate release was linear for more than 1 h and dependent on the intracellular hydrolysis of organic phosphate esters. In uremics on chronic hemodialysis total phosphate release was significantly increased suggesting an elevated RBC energy metabolism. Ouabain-sensitive phosphate release, however, was decreased. For RBCs of controls and uremic subjects approximately 80% of inorganic phosphate liberated within the cell was recycled. Thus, RBC phosphate release represents 20% of intracellular phosphate ester metabolism. In uremia active electrolyte transport was diminished, suggesting an impaired Na-K-ATPase activity. It resulted in an increased RBC sodium and a decreased potassium concentration. The positive correlation between ouabain-sensitive rate constant for sodium efflux and ouabain-sensitive RBC phosphate release indicates that ouabain inhibition of phosphate elimination might be related to Na-K-ATPase. In RBCs of uremic subjects almost 4% of the increased energy metabolism was needed for active electrolyte transport mechanisms, in control RBCs 12% was required.
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PMID:Red blood cell sodium transport and phosphate release in uremia. 630 46

In acutely uremic animals, the contractile force of the heart is consistently increased; such an increase can be dissociated from changes of afterload or catecholaminergic drive. It is associated with diminished sarcolemmal Na,K-ATPase activity in the heart which, in turn, may be related to increased levels of endogenous digitalis-like substances (endigens) that have been postulated to represent a natriuretic factor. In patients with chronic uremia, myocardial contractility is usually normal, but occasionally there may be heart failure unrelated to pre-existing hypertension, coronary heart disease, anemia, fluid overload, or other recognizable factors. So far, the experimental basis for this clinical observation is uncertain. Possible causes for the clinical syndrome include an excess of parathyroid hormone or cardiodepressor substances. There is experimental evidence of impaired cardiac response to beta adrenergic agonists, e.g., decreased isoproterenol-dependent calcium uptake, diminished inotropic and chronotropic responses. In acutely uremic rats, cardiac cyclic AMP levels are high but can be reversed by beta blockers. Heart calcium content is variable and heart weight is constantly increased in acutely uremic rats, despite decreased skeletal muscle mass. The change in heart weight is not related to anemia, to an excess of parathyroid hormone, or to sympathetic activity; its cause remains unknown. Experimental studies to date have shown a variety of abnormalities, but do not provide a uniform concept of the mechanisms or an explanation for the cardiac dysfunction so often observed in patients with uremia.
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PMID:Cardiac function in experimental uremia. 636 51

Calcium ATPase, an enzyme involved in intestinal calcium transport, was measured in homogenates of duodenal mucosal scrapings of normal and uremic rats. The effects of calcium deprivation and treatment with 1 alpha,25-dihydroxycholecalciferol [1,25-(OH)2D3] were investigated as well. Uremia decreased the enzyme activity and impaired the rise after calcium deprivation as observed in intact rats. The 1,25-(OH)2D3 treatment increased the enzyme activity in uremic animals and resulted in an identical response to calcium deprivation as observed in intact rats; parathyroidectomy abolished this effect. A striking correlation between everted duodenal gut sac calcium transport and calcium ATPase activity could be demonstrated for all groups of rats studied. It is concluded that the calcium ATPase activity is linked to the production of 1,25-(OH)2D3 as well as to an additional factor, probably parathyroid hormone. The close relationship between enzyme activity and in vitro calcium transport, even during constant physiological supplementation with 1,25-(OH)2D3, suggests an autonomous role of the calcium ATPase activity for mediation of calcium transport in the duodenum in addition to the well-known mechanisms related to vitamin D and its metabolites.
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PMID:Calcium ATPase and intestinal calcium transport in uremic rats. 644 89

Erythrocytes from 15 uremic children aged from 7 months to 16 years were analyzed for adenosine triphosphatase (total ATPase and ouabain sensitive ATPase i.e. Na+, K+-ATPase), sodium and potassium ions and ATP concentration, in some cases before and after therapeutic measures had been undertaken. No correlation was found between the levels of Na+, K+-ATPase and serum creatinine and all uremic children had Na+, K+-ATPase levels within the range for normal children. The children with rapidly progressive uremia had higher activities of Na+, K+-ATPase at the corresponding serum creatinine concentration than those with slowly progressive uremia. Longitudinally the Na+, K+-ATPase activities fell and the erythrocyte Na+-K+ ratio increased in slowly progressive uremia. Introduction of a low-protein, high-energy diet giving accelerated growth did not change the Na+, K+-ATPase activities, the concentrations of erythrocyte sodium and potassium ions or ATP. Hemodialysis gave a slight increase of Na+, K+-ATPase and of the erythrocyte Na+-K+ ratio, whereas renal transplantation resulted in a remarkable increase of Na+, K+-ATPase activity and decrease of Na+-K+ ratio. A distinct feature of uremic children with hypertension was a low erythrocyte Na+-K+ ratio and a high Na+, K+-ATPase level.
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PMID:Characteristics of active sodium and potassium transport in erythrocytes in children with different stages of symptomatic uremia. 645 27

The high incidence of cardiac complications in endstage renal failure is not only related to the chronic pressure load of the left ventricle, although the proportion of patients with elevated blood pressure increases from 53 to 81% as reno-parenchymal disease progresses. Other factors as anemia, hyperparathyroidism, autonomic neuropathy and retention of electrolytes, metabolic products of toxins may cause damage to the heart. It is a matter of discussion whether uremia itself causes cardiomyopathy. Findings of a reduced Ca++-uptake during beta-adrenergic stimulation and a reduced reaction of (Na+, K+)-ATPase to digitalis suggest a basic change of myocardial membrane metabolism. Retention of an "endogenous digitalis" could help to explain some contradictory results.
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PMID:[Reno-cardiac interactions in kidney failure (author's transl)]. 700 26


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