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)

Chronic renal failure in the rat is associated with an impaired extrarenal potassium handling, whereas a renal adaptive mechanism of the remaining nephrons has been described. To understand the molecular basis of potassium homeostasis during renal failure we investigated the in vitro pump activity and the catalytic mRNA transcription in three different tissues: skeletal muscle, isolated adipocytes and kidney. The activity of the sodium pump, as measured by ouabain-sensitive 86Rb/K uptake in isolated adipocytes and skeletal muscle fibers, revealed a significant reduction of the pump activity in uremic rats. The reduction of the Na, K-ATPase activity in adipose tissue was associated with a similar decrement of both catalytic subunits (alpha 1 and alpha 2), whereas in the skeletal muscle tissue was only related to a decrease in the activity of the alpha 1 isoform. The expression of rat Na, K-ATPase catalytic isoforms mRNAs in kidney, muscle and adipose tissue from control and chronic renal failure rats was investigated at the molecular level with cDNA probes specific for the catalytic isoforms (alpha 1 and alpha 2). Northern blot analysis revealed that the respective catalytic mRNAs of uremic rats are regulated in a tissue-specific manner that are in agreement with the sodium-potassium pump activity. Muscle and adipose tissue showed a decrement in the levels of expression for the alpha 1 isoform mRNA. In contrast to these tissues, an increment in alpha 1 mRNA expression was observed in the kidney of rats with chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue-specific modulation of Na, K-ATPase alpha-subunit gene expression in uremic rats. 819 69

Our previous studies indicate that impaired function of skeletal muscle limits the exercise tolerance of patients with end-stage renal failure who are either maintained on dialysis or undergo renal transplantation. To study the morphology of the condition, muscle biopsies were performed on eight patients with renal failure-associated myopathy. Control samples were taken from seven healthy athletes undergoing knee surgery and from five otherwise healthy but untrained subjects. Tissues were examined by routine light and transmission electron microscopy. Histochemical staining of frozen sections for myosin adenosine triphosphatase and quantitative computer-assisted morphometry of the fiber type and size was performed. The mean (+/- SD) size for type I fibers in patients was 61.2 +/- 11.8 microns, while type II fibers measured 46.7 +/- 11.4 microns. The mean percentage of type II fibers was 67% +/- 12%. These values are within the normal population range and were not different from controls. Significant changes were found on light microscopy of patient samples. These included fiber splitting, internalized nuclei, nuclear knots, moth-eaten fibers, fiber degeneration and regeneration, increased content of lipid droplets, and fiber-type grouping. Electron microscopy showed a large variety of nonspecific abnormalities, including mitochondrial changes, Z-band degeneration, myofilament loss, and accumulation of intracellular glycogen. Ten of 12 control subjects showed no such changes; minor abnormalities were noted on both light and electron microscopy in the remaining two subjects. Muscle oxidative capacity (19.5 +/- 5.1 microL O2/min) for patients with end-stage renal failure was not different from values for those who had undergone renal transplantation, but was lower than values found in trained athletes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphologic features of the myopathy associated with chronic renal failure. 823 13

In normal adults eating diets with standard protein contents, urinary excretion of NH4 approximates 40 mmol/24 hours and urinary pH is variable. In patients with metabolic acidosis, a urinary pH under 5.5 suggests an extra-renal cause whereas a urinary pH above 5.5 suggests a renal disorder, although there are many exceptions to this rule of thumb. However, urinary excretion of NH4 is always above 70 mmol/24 hours in extra-renal acidosis and less than or equal to 40 mmol/24 hours in renal acidosis; the two situations can readily be differentiated by determining the urinary anion gap which is absent in the former case and present in the latter. Acidosis due to nephron loss is readily diagnosed on the basis of advanced renal failure with an elevation in nonassayed plasma anions, contrasting with the increased serum chloride level found in tubular acidosis. Oral NaHCO3 loading followed by determination of the fractional excretion of HCO3 or, preferably, of the TmHCO3 normalized for glomerular filtration rate differentiates proximal tubular acidosis (decreased TmHCO3) from distal tubular acidosis (normal or increased TmHCO3). In the latter case, decreased serum potassium levels suggest distal tubular acidosis due to defective H(+)-ATPase or H+/K(+)-ATPase pump function (no increase in urinary PCO2 after oral NaHCO3 loading) or to inability of the kidney to develop a normal H+ gradient (normal increase in urinary PCO2). Increased serum potassium levels suggest conditions involving either hypoaldosteronism or alterations in transepithelial voltage or pseudo-hypoaldosteronism. The incidence of distal tubular acidosis with increased serum potassium levels is rising, whereas tubular acidosis with low serum potassium levels remains infrequent.
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PMID:[Classification of renal tubular acidosis. Recent data]. 838 29

Skeletal muscle energetics can be studied noninvasively at rest, during exercise, and in recovery using phosphorus nuclear magnetic resonance (31P-NMR). In resting muscle, inorganic phosphate (P(i)) and total cellular phosphate concentration are regulated by Na(+)-dependent P(i) transport. Insulin was shown to stimulate P(i) uptake in G-8 muscle cells, in isolated rat soleus muscle, and in human muscle in vivo under conditions of hyperinsulinemic-euglycemic clamp. The relationship between plasma P(i) and intracellular muscle P(i) was examined in a group of patients with elevated plasma P(i) resulting from renal failure. The total creatine content of muscle cells is controlled by an active creatine uptake in which beta 2-receptor stimulation and the activity of the Na(+)-K(+)-ATPase play a significant role. Recovery after exercise is entirely oxidative; the rate of ATP synthesis is largely controlled by ADP, the concentration of which is determined by the creatine kinase equilibrium that includes the concentration of H+. At the onset of aerobic dynamic exercise, ATP is maintained largely by glycolysis, producing lactic acid, and by phosphocreatine breakdown. After vasodilation, ATP synthesis becomes predominantly oxidative. The above processes can be quantitatively evaluated by 31P-NMR.
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PMID:Control of energy metabolism during muscle contraction. 852 7

Tubular overwork is thought to be a promoter of the tubular hypertrophy and renal failure that occur in response to renal mass reduction. Because Na-K-adenosinetriphosphatase (Na-K-ATPase) is an index of tubular work, we evaluated the effects of subtotal nephrectomy and of enalapril therapy, which delays the evolution of renal lesions, on tubular hypertrophy and Na-K-ATPase activity along the rat nephron. Within 6 wk, 70% reduction of renal mass engendered hypertrophy of the proximal convoluted tubule (PCT), thick ascending limb (TAL), and collecting duct (CD), as well as parallel increments in Na-K-ATPase activity per millimeter tubule length (Na-K-ATPase activity per unit surface area was not modified by subtotal nephrectomy). Chronic enalapril therapy prevented part of the hypertrophy (but not Na-K-ATPase stimulation) of the PCT and the whole stimulation of Na-K-ATPase (but not hypertrophy) in the CD, whereas it had no effect on the TAL. Enalapril effect on Na-K-ATPase in CD might result from reduced bradykinin metabolism, as the reduction in urinary excretion of bradykinin observed in subtotally nephrectomized rats was prevented by enalapril therapy.
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PMID:Na-K-ATPase along rat nephron after subtotal nephrectomy: effect of enalapril. 876 19

We have isolated a labile, specific sodium pump inhibitor or digitalis-like factor from the peritoneal dialysate of volume-expanded renal failure patients whose levels correlated closely with volume status and blood pressure. This study characterizes the inhibitory profile of this agent compared with that of ouabain against the three alpha-isoforms of the sodium pump. We prepared microsomal Na,K-ATPase from rat tissues representing the highest proportion of one of the alpha-isoforms. Both Northern and Western blot analyses confirmed that kidney had predominantly the alpha1-isoform, skeletal muscle the alpha2-isoform, and fetal brain the alpha3-isoform. Ouabain (5 x 10(-6) mol/L) produced little inhibition of kidney Na,K-ATPase (3.4+/-2.0%) but significant inhibition of skeletal muscle (37.2+/-3.7%, P<.001) and fetal brain (38.8+/-3.5%, P<.001) activity. In contrast, the labile digitalis-like factor, causing comparable inhibition of fetal brain Na,K-ATPase activity (33.3+/-4.7%), produced markedly greater inhibition of kidney (42.5+/-5.6%, P<.001) and moderately greater inhibition of skeletal muscle pump activity (57.7+/-6.3%, P<.05). In addition, the labile digitalis-like factor produced a marked concentration-dependent inhibition of the alpha2- and alpha3-isoforms (r=.79, P=.00005). Experiments combining the labile digitalis-like factor and ouabain confirmed that digitalis-like factor, unlike ouabain, was an effective inhibitor of all three isoforms in rat, in particular alpha2. The different pattern of isoform sensitivity displayed by the labile digitalis-like factor and ouabain further differentiates the two agents and raises some interesting possibilities about the functional implications of the endogenous factor.
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PMID:Sodium pump isoform specificity for the digitalis-like factor isolated from human peritoneal dialysate. 936 92

Looking for causes or consequences of primary hypertension much attention is drawn to the ion transport systems of the cellular membrane. The existence of endogeneous digitalis-like factors, that lower the activity of Na+/K(+)-ATPase and result in a complex change of electrolyte balance of cells are discussed as a reaction of the organism to salt and volume retention. The measurement of passive permeability of erythrocyte membranes for potassium is an easy and useful method for the detection of disturbances of Na+/K(+)-transport, especially for extensive screening investigations. We examined the potassium permeability of erythrocytes in healthy individuals (GR1, n = 48), patients with compensated renal insufficiency (GR2, n = 36) and diabetics (GR3, n = 25) as well as a group of diabetics with renal failure (GR4, n = 47). The relative change of potassium concentration in the whole blood, based on the efflux of potassium during a 4-hour-incubation at 37 degrees C, is defined as a measure for K(+)-permeability. K(+)-concentrations are determined every 60 minutes with ion sensitive electrodes. K(+)-permeability was significantly increased in patients with compensated renal insufficiency compared to the control group and to diabetics. Diabetics differed markedly in their erythrocyte reaction regarding K(+)-permeability. Whereas patients with renal insufficiency show an efflux of potassium during investigation there is a decrease of potassium in plasma in diabetics. The K(+)-permeability results of patients with both diseases are intermediate between the GR2- and GR3 results and are significantly different from the control group. When g-strophanthin is added to inhibit the sodium pump, the differences between the groups are abolished. The decreased K+permeability in diabetics compared to the control group could be explained by the increased supply of energy-rich substrates for the Na+/K(+)-ATPase.
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PMID:K(+)-permeability in diabetics and nondiabetics with and without renal insufficiency. 928 37

The activity of the plasma membrane Ca2+ ATPase of chronic renal failure patients is decreased by circulating inhibitors yet to be characterized. In this study, inhibitors of Ca2+ ATPase were isolated from ultrafiltrate of patients with end-stage renal failure. They were identified as dimethylguanosine, phenylethylamine, and phenylacetic acid by chromatography and mass spectrometry. Ca2+ ATPase activity was measured spectrophotometrically as the difference in hydrolysis of ATP in the presence and absence of Ca2+ with different concentrations of ATP and the isolated substances. All of the identified compounds are sufficiently lipophilic to penetrate the blood-brain barrier and to accumulate in cerebral tissue. The inhibitory effects of these agents were additive. The apparent K(m) values for ATP and Ca2+ were not altered by these substances, suggesting a noncompetitive mechanism of inhibition. In plasma of healthy subjects, the substances were not detectable. The Ca2+ ATPase inhibitors identified may play a role in the pathophysiology of end-stage renal failure and, potentially, in monitoring toxic effects on cellular Ca2+ metabolism in renal failure.
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PMID:Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as inhibitors of Ca2+ ATPase in end-stage renal failure. 964 35

The renal functional changes following infusion of dopamine are well documented. The most pronounced effect is the increase in renal blood flow and a marked natriuretic response. Due to its specific renal effects, dopamine has become one of the most frequently used drugs in the treatment of critically ill patients with low cardiac output states and/or acute oliguric renal failure. Pharmacological effects of dopamine are dose dependent. Low doses of dopamine predominantly stimulate dopaminergic receptors, but with increasing doses actions secondary to stimulation of adrenergic beta(1) and alpha receptors also appear. Dopamine receptors are classified into the D1 and the D2 subtype families. Stimulation of D1 receptors increases adenylate cyclase activity and intracellular levels of cAMP, whereas D2 receptor activation decrease or do not change adenylate cyclase activity. In the kidney, dopamine receptors have been localized in the renal vasculature except in glomeruli and in the tubules (the proximal tubule > macula densa > the loop of Henle > the distal tubule > collecting ducts). The postsynaptic D1 receptor mediates vasodilation by a direct mechanism, whereas the presynaptic D2 receptor indirectly may dilate the vessels by inhibition of norepinephrine release. Consistent with previous results in animals, the present haemodynamic studies revealed that dopamine in normal subjects elicits a dose dependent biphasic effect on the mean arterial blood pressure. With 1 and 2 micrograms/kg/min, a depressor effect resulted from a decrease in the diastolic pressure, whereas a pressor effect, seen with doses at and above 7.5 micrograms/kg/min, was mainly caused by elevations of the systolic pressure. The studies indicated that the increase in cardiac output at low doses of dopamine is secondary to a decrease in peripheral vascular resistance, independent of effects of beta(1) receptors on cardiac contractility and heart rate. Dose-response studies demonstrated that the dopamine-induced increase in effective renal plasma flow (ERPF) reaches its maximum at 3 micrograms/kg/min. The increase in ERPF remained unchanged by pretreatment with metoprolol, and a comparison of dopamine and dobutamine in doses producing similar increases in cardiac output demonstrated that only dopamine increased ERPF. These findings indicate that indirect haemodynamic effects secondary to increases in cardiac contractility and cardiac output do not contribute significantly to the increase in renal perfusion caused by dopamine. In normal subjects, acute hypoxaemia attenuated the renal vasodilating effect of dopamine. The well known natriuretic effect of dopamine was significantly expressed in all of our studies, in which doses ranging from 1 to 5 micrograms/kg/min caused about a two-fold increase in sodium excretion. At doses at and above 7.5 micrograms/kg/min which increased mean arterial pressure, dopamine further increased sodium clearance (CNa) while ERPF was decreasing, indicating the contribution of pressure natriuresis at these high doses. Although not affecting the percentage increase in CNa, metoprolol suppressed the absolute, maximal response to non-pressor doses of dopamine, suggesting that a reduced adrenergic beta(1) receptor activity may indirectly affect the natriuretic response, probably by decreasing renal perfusion pressure. Previous studies in animals demonstrated that dopamine natriuresis can occur independent of increases in ERPF and GFR, and, furthermore, that the response can be abolished by specific D1 receptor antagonists. Evidence obtained by in vitro studies indicated that dopamine via D1 receptors may inhibit the Na(+)-H+ antiport at the brush-border membrane of proximal tubular cells and the Na(+)-K(+)-ATPase activity at basolateral membranes of both the proximal tubule and the medullary thick ascending limb of the loop of Henle. (ABSTRACT TRUNCATED)
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PMID:Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans. 967 40

Endogenous Na, K pump inhibitors may contribute to the pathogenesis of hypertension, and could do so by causing direct vasoconstriction and/or enhancing sensitivity to other vasoconstrictor agents. These effects of the Na, K pump inhibitors are likely due to inhibition of Na-K-ATPase. In turn, cells become depolarized, internal sodium concentration increases and internal calcium is increased by exchange for sodium via the sodium/calcium exchange carrier. This extra calcium is sequestered, increasing the size of the releasable intracellular calcium pool. Both depolarization and the increase in cytosolic calcium can cause vasoconstriction. Both depolarization and the increased size the intracellular calcium pool can sensitize the blood vessel to other vasoconstrictor agents. Endogenous pump inhibitors may also stimulate the release of catecholamines from the intramural sympathetic nerve terminals. Studies of a variety of candidate endogenous Na, K pump inhibitors are reviewed. These include presently unidentified substances extracted from human urine, from peritoneal dialysate of hypertensives with renal failure, and from bovine and rat hypothalamus. Additional candidate compounds include ouabain, selected pregnanes and marinobufagenin, a steroid originally identified in the venom of the frog, Bufo marinus.
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PMID:Summary of studies of changes in vascular reactivity caused by natriuretic hormones. 968 26


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