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)

The impact of low level lead exposure on human central nervous system function is a major public health concern. This study addresses the inhibition of the cation pump enzyme Na, K-ATPase by low level lead. Human brain tissue was obtained at autopsy and frozen until use. Brain homogenates were preincubated with PbCl2 for 20 min at 0 degrees C. Inhibition of K-paranitrophenylphosphatase (pNPPase), a measure of the dephosphorylation step of Na,K-ATPase, reached steady state within 10 min. K-pNPPase activity, expressed (mean +/- SEM) as a percentage of control (45.2 +/- 2.7 nmol/mg/min), fell to 96.3 +/- 0.9% at 0.25 uM [PbCl2] to 82.0 +/- 1.6% at 2.5 uM [PbCl2] in homogenates prepared from normal brain. Similar results were obtained with homogenates prepared from brains of patients with a history of alcohol abuse and of those with other miscellaneous conditions. Since the mean blood level of lead in the United States has ranged recently from 9.2 to 16.0 ug/dl (0.44 to 0.77 uM), these results indicate that current in vivo levels of lead exposure may impair important human brain function.
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PMID:Low level lead inhibits the human brain cation pump. 185 20

The exchange of intramitochondrial ATP (ATP(in)) for extramitochondrial ATP (ATP(out)) was measured by using 31P NMR spectroscopy over a range of temperatures in isolated rat liver mitochondria oxidizing glutamate and succinate in the presence of external ATP but no added ADP (state 4). The rate of this exchange is more than an order of magnitude faster than rates reported previously that were determined by using isotopic techniques in the presence of oligomycin, the potent ATPase inhibitor. Differences are ascribed in part to the low levels of matrix ATP present in oligomycin-treated mitochondria. The addition of oligomycin to mitochondrial suspensions decreases intramitochondrial ATP levels from 17 +/- 3 (SEM) nmol/mg of protein in state 4 to 1.51 +/- 0.1 nmol/mg of protein in the presence of inhibitor at 8 degrees C. Simultaneously, transporter flux falls from 960 +/- 55 nmol/min.mg to undetectable levels (less than 300 nmol/min.mg). Although transport rates are much faster when measured by saturation-transfer than by conventional isotopic methods, the enthalpy values obtained by determining the effect of temperature on flux are very similar to those reported in the past that were determined by using isotopic techniques. Intramitochondrial ATP content regulates the rate of the ATP(in)/ATP(out) exchange. At 18 degrees C, the concentration of internal ATP that produces half-maximal transport rate is 6.6 +/- 0.12 nmol/mg of mitochondrial protein. The relationship between substrate concentration and flux is sigmoidal and is 90% saturated at 11.3 +/- 0.18 nmol/mg of mitochondrial protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:31P NMR saturation-transfer study of the in situ kinetics of the mitochondrial adenine nucleotide translocase. 188 22

In 15 conscripts, venous plasma potassium was followed during exercise on a training bicycle before and after 10 weeks of moderate physical training and a putative relationship with skeletal muscle Na,K-ATPase was evaluated. Peak plasma potassium concentration obtained at exhaustion was 6.1 +/- 0.2 and 5.6 +/- 0.2 mmol l-1 (mean +/- SEM, n = 14, P less than 0.05) before and after training, respectively. Throughout the exercise period and within the first minutes of rest plasma potassium concentration was 0.2-0.5 mmol l-1 higher before than after training. Neither peak values nor peak rises in plasma potassium concentration before nor after training were correlated to the 3H-ouabain binding site (Na,K-ATPase) concentration in vastus lateralis muscle. The results indicate that net loss of potassium from the skeletal muscle pool during exercise is reduced after training, that the heart during exercise may be exposed to a smaller rise in plasma potassium concentration after training than before, and that moderate improvement of capacity to clear extracellular potassium during exercise may be due to increased activity of existing Na,K-pumps in resting skeletal muscle fibres. This may reduce muscle fatigue, increase physical performance and explain the paradoxical observation that, despite an increased catecholamine response, there is a reduced risk of cardiac events after training.
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PMID:Exercise-induced hyperkalaemia can be reduced in human subjects by moderate training without change in skeletal muscle Na,K-ATPase concentration. 196 26

Male Wistar rats were killed 1, 2, or 4 days after a single intraperitoneal injection of cisplatin (5 mg/kg). Functional renal indices, enzymatic activities, and morphological variables were studied. One day after the injection, the treated group showed an increase in the magnesium and phosphate fractional urinary excretion (FE) vs the control group (FE Mg = 5.2 +/- SEM 0.5% vs 13.0 +/- 1.7%; P less than 0.01; and FE P = 4.7 +/- 0.7% vs 14.0 +/- 1.9%; P less than 0.01). Two days after cisplatin administration, a decrease in creatinine clearance of treated animals was found, to 0.33 +/- 0.03 vs 0.51 +/- 0.03 ml/min; P less than 0.05. Na-K-ATPase and ouabain-insensitive ATPase activities were studied in the proximal convoluted tubule, the medullary thick ascending limb of the Henle's loop (mTAL), and the distal convoluted tubule. Only in mTAL one day after the cisplatin injection was there a decrease in Na-K-ATPase activity in the treated group vs controls (1103 +/- 145 vs 1734 +/- 189 pmol Pi/mm.h; P less than 0.05). Morphological studies showed a decrease in mTAL diameters on day 1, and an increase in proximal convoluted tuble diameters at day 2 of treated rats vs controls, at 27.8 +/- 0.6 vs 31.4 +/- 0.7 microns; P less than 0.05, and 50.4 +/- 1.2 vs 47.4 +/- 0.2 microns; P less than 0.05 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of acute cisplatin administration on renal ATPase activities and magnesium excretion of rats. 196 57

1. We have used n.m.r. spectroscopy to measure rubidium concentrations in the skeletal muscle of live intact rats. Using a 1.9 T superconducting magnet and an ear-phone coil tuned to both protons (1H) and rubidium (87Rb), it was possible to make measurements of both tissue rubidium content and water content, and from these measurements to obtain the rubidium concentration. 2. The n.m.r. estimate of rubidium concentration in muscle in vivo was found to be a constant 31% (SEM 4%) of that estimated by flame atomic absorption spectroscopy in an extract of excised muscle. This is close to the predicted theoretical n.m.r. visibility of 33%. The visibility was constant for muscle rubidium concentrations ranging between 10 and 34 mmol/l. 3. Rubidium concentration measurement by this method is unaffected by variations in sample geometry, sample volume, tissue conductivity, coil tuning and amplifier gain. 4. By using this method to measure changes in tissue rubidium concentration with time in the same animal, it should now be possible to assess the activity of ion transport systems, such as sodium- and potassium-activated adenosine triphosphatase in vivo, by measuring the rates of change of tissue rubidium concentrations during the administration of rubidium salts. 5. This method could also be used to measure the absolute concentration of any n.m.r.-visible nucleus and could be applied to man.
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PMID:A non-invasive method of measuring concentrations of rubidium in rat skeletal muscle in vivo by 87Rb nuclear magnetic resonance spectroscopy: implications for the measurement of cation transport activity in vivo. 215 50

Na,K-ATPase concentration was measured by vanadate facilitated 3H-ouabain binding to intact samples taken from various parts of porcine and canine myocardium. In porcine and canine heart 3H-ouabain binding site concentration in ventricles was 1.4-2.5 times larger than in atria. Evaluation of 3H-ouabain binding kinetics revealed no major difference between atria and ventricles: Equilibrium was obtained after the same incubation time in right atrium (RA) as in left ventricle (LV), both in porcine and canine heart. Unspecific uptake and retention of 3H-ouabain was for porcine heart RA and LV 1.5 and 1.4, respectively, and for canine heart RA and LV, both 1.2% filling (i.e., volume (ml) of incubation medium 3H-radioactivity taken up per mass unit (g wet wt.) of tissue multiplied by 100). The apparent dissociation constant (KD) was 1.4 x 10(-8) and 1.9 x 10(-8) in porcine RA and LV and 2.6 x 10(-8) and 6.1 x 10(-8) mol/l in canine RA and LV. Loss of specifically bound 3H-ouabain during the washout procedure occurred with a half-life time (T1/2) of 16.7 and 28.6 in RA and LV of porcine heart and 91.2 and 151.6 h in RA and LV of canine heart. Duly corrected for these errors of the method--factor 1.16 and 1.13, respectively, for porcine RA and LV, and factor 1.11 and 1.13 for canine RA and LV, total 3H-ouabain binding site concentration was found to be 553 +/- 74 and 1037 +/- 45 pmol/g wet wt. (means +/- SEM, n = 5) in porcine RA and LV, and 569 +/- 37 and 1410 +/- 40 pmol/g wet wt. (means +/- SEM, n = 5) in the canine RA and LV. These values were confirmed by measurements of 3H-digoxin binding to the porcine heart. The present quantification of myocardial Na,K-ATPase gives values up to 154 times higher than measurements based upon Na,K-ATPase activities in membrane fractions where the recovery of Na,K-ATPase may be less than 1% due to loss during purification. A higher Na,K-ATPase concentration is found in small animals than in large animals. A relationship between higher concentration of Na,K-ATPase and larger pressure work in ventricles compared to atria is suggested. Myocardial 3H-ouabain binding sites were found to be stable for 20 min of ischemia, followed by 1 h of reperfusion, supporting the concept that myocyte injury induced by short term ischemia may be reversible and that reperfusion may result in normalization.
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PMID:Quantification of the total Na,K-ATPase concentration in atria and ventricles from mammalian species by measuring 3H-ouabain binding to intact myocardial samples. Stability to short term ischemia reperfusion. 217 46

1. The kidney taken from a rat rendered nephrotic by exposure to puromycin aminonucleoside retains sodium abnormally when perfused in isolation and has an abnormally low vascular resistance (J. D. Firth et al., Clin. Sci. 1989; 76, 387-95). In this study the relation of oxygen consumption to sodium reabsorption has been examined in the isolated nephrotic organ, which has also been exposed to a variety of natriuretic agents and to the effect of inhibition of metabolism by cooling, in an attempt to discern the transport process, or processes, responsible for abnormal tubular handling of sodium. In addition, the effects of three endogenous vasoconstrictors, noradrenaline, angiotensin II and endothelin, on the function of the isolated nephrotic kidney have been examined. 2. The ratio of mol of sodium reabsorbed by the tubules of the isolated nephrotic kidney to mol of oxygen consumed was reduced in comparison with the control kidney (means +/- SEM): 9.22 +/- 0.97 versus 15.43 +/- 1.55 (P less than 0.002). 3. In the presence of ouabain (1 mmol/l), acetazolamide (1 mmol/l), frusemide (200 mumol/l), the combination of these three agents together, hydroflumethiazide (100 mumol/l), benzamil (100 nmol/l) or atrial natriuretic peptide (1000 pmol/l), a lesser increment in sodium excretion was induced in the isolated nephrotic kidney than in the control kidney and the nephrotic organ continued to excrete less sodium in both absolute and fractional terms. 4. This suggests that enhanced tubular sodium reabsorption in the isolated nephrotic kidney does not depend upon abnormally increased activity of the Na+/K(+)-adenosine triphosphatase, bicarbonate-dependent sodium transport, Na+/K+/2Cl- co-transport, electrically neutral proportionate reabsorption of sodium and chloride (distal tubule), epithelial sodium channel (distal tubule) or atrial natriuretic peptide-sensitive sodium transport processes. 5. When isolated nephrotic kidneys and normal kidneys were cooled to 8-10 degrees C the handling of sodium became virtually identical in the two groups. On re-warming to 37 degrees C, the original differences in sodium handling between nephrotic and control kidneys were restored. This implies that the mechanism responsible for the abnormal tendency to retain sodium is temperature-sensitive; as yet it remains otherwise undefined. 6. The sensitivity of the renal vessels to noradrenaline, angiotension II and endothelin, as judged by the percentage reduction in perfusate flow rate produced by a given concentration of any of these agents, was not substantially altered in the nephrotic kidney compared with the control kidney. Increase in vascular tone was not associated with amelioration of the tendency of the isolated nephrotic organ to retain sodium. Increasing concentrations of angiotensin II caused the filtration rate to increase in the nephrotic kidney. This effect was unexpected: in the control preparation, as anticipated, angiotensin II caused the filtration rate to decrease.
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PMID:Effect of natriuretic agents, vasoactive agents and of the inhibition of metabolism on sodium handling in the isolated perfused kidney of the nephrotic rat. 217 43

Leucocyte ouabain-sensitive 22Na+ efflux was studied in 35 normal and 12 obese subjects. This efflux rate constant was raised in the obese (2.72 +/- SEM 0.13 vs 2.31 +/- 0.08 h-1, P less than 0.006), indicating a higher activity of the sodium pump in vivo, There was a significant correlation between this efflux rate constant and fasting insulin level in both the whole population and in the normals alone (rs = 0.36, P less than 0.007, and rs = 0.40, P less than 0.009 respectively). A hyperinsulinaemic-euglycaemic clamp was performed on seven normal volunteers. After 2 h, there was a significant stimulation of the leucocyte efflux rate constant (from 2.86 +/- 0.17 to 3.33 +/- 0.18 h-1, P less than 0.01). In-vitro incubation of leucocytes with insulin produced a maximal stimulation of the Na+-K+-ATPase activity of about 35% at 2 h with half-maximal stimulation achieved at 46 mU/l. Insulin (100 mU/l) also stimulated the leucocyte ouabain-sensitive 22Na+ efflux rate constant in vitro by about 11% with or without 1 h of preincubation with the insulin. These findings may explain the hypokalaemic and sodium retaining effects of insulin in man; they may also partially explain the raised Na+ efflux rate constants in obesity.
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PMID:The leucocyte sodium pump in healthy and obese subjects: the association of insulin with its activity. 244 7

The effects of nerve growth factor (NGF) on induction of Na+,K+-ATPase were examined in a rat pheochromocytoma cell line, PC12h. Na+,K+-ATPase activity in a crude particulate fraction from the cells increased from 0.37 +/- 0.02 (n = 19) to 0.55 +/- 0.02 (n = 20) (means +/- SEM, mumol Pi/min/mg of protein) when cultured with NGF for 5-11 days. The increase caused by NGF was prevented by addition of specific anti-NGF antibodies. Epidermal growth factor and insulin had only a small effect on induction of Na+,K+-ATPase. A concentration of basic fibroblast growth factor three times higher than that of NGF showed a similar potency to NGF. The molecular form of the enzyme was judged as only the alpha form in both the untreated and the NGF-treated cells by a simple pattern of low-affinity interaction with cardiotonic steroids: inhibition of enzyme activity by strophanthidin (Ki approximately 1 mM) and inhibition of Rb+ uptake by ouabain (Ki approximately 100 microM). As a consequence, during differentiation of PC12h cells to neuron-like cells, NGF increases the alpha form of Na+,K+-ATPase, but does not induce the alpha(+) form of the enzyme, which has a high sensitivity for cardiotonic steroid and is a characteristic form in neurons.
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PMID:Nerve growth factor induces Na+,K+-ATPase in a nerve cell line. 244 35

The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactivity with digoxin-antibodies (57.5 +/- 5.0 vs. 42.1 +/- 3.8 pg/ml, p less than 0.02); inhibition of kidney Na+, K+-ATPase activity (135 +/- 5 vs. 154 +/- 5 mumol/mg/h, p less than 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 +/- 0.40 vs. 7.68 +/- 0.34 mmol/L cells/h, p less than 0.01)]; (2) reduced Na+, K+-pump activity (7.34 +/- 0.29 vs. 10.88 +/- 0.41 mmol/L cells/h, p less than 0.001) and increased Na+ content (4.66 +/- .08 vs. 4.16 +/- 0.11 mmol/L cells, p less than 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 +/- 0.9 vs. 12.6 +/- 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 +/- 4 mm Hg (mean +/- SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous "digitalis-like" compounds, and a partial recovery of Na+, K+-pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous "digitalis-like" compounds.
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PMID:Antihypertensive effect of canrenone in a model where endogenous ouabain-like factors are present. 245 Feb 60


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