Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major evidence against the hypothesis that Na+, K+-adenosine triphosphatase (Na+, K+-ATPase) inhibition is the mechanism of the positive inotropic action of digitalis is that the myocardial sodium content does not increase at the time of the inotropic response. In order to understand the relationship between sodium pump inhibition and myocardial sodium content, a computer simulation of the intracellular sodium concentration ([Na+]i) during a cycle of myocardial function was performed. The model for the computer simulation is a small compartment adjacent to the inner surface of the sarcolemma. The change in [Na+]i in this compartment is determined by the rate of sodium influx (published data utilized) and the rate of active sodium transport was estimated from the activities of partially purified dog heart Na+, K+-ATPase preparations assayed with various concentrations of sodium and ouabain. The initial rapid sodium influx results in maximal sodium pump activation, but the pump activity decreases with time as the [Na+]i decreases. Thus, the sodium pump functions at a rate close to its maximal velocity during the initial phase of each cycle but at reduced rates during the later phase. Inhibition of Na+, K+-ATPase by ouabain decreases the maximal velocity during the intiial phase of each cycle but at reduced rates during the later phase. Inhibition of Na+, K+-ATPase by ouabain decreases the maximal velocity of the sodium pump but increases the time in each cycle at which the sodium pump operates at its highest possible rate under these conditions, i.e., a rate close to the inhibited maximal velocity. A 40% inhibition of Na+, K+-ATPase activity, caused by inotropic concentrations of ouabain, increases the peak [Na+]i but fails to cause intracellular sodium accumulation since [Na+]i approaches control levels before the beginning of the next cardiac cycle. With greater enzyme inhibition, caused by arrhythmic concentrations of ouabain, [Na+]i fails to return to the precycle level and thus each subsequent cycle causes a progressive accumulation of myocardial sodium. Computer simulation predicts that a positive inotropic concentration of ouabain causes a myocardial sodium accumulation at a high heart rate but not at a lower heart rate. This was confirmed by experiments with Langendorff preparations of guinea-pig hearts. It is concluded that a moderate sodium pump inhibition by inotropic concentrations of ouabain enhances the intracellular sodium transient (a transient increase in intracellular sodium concentration associated with each membrane excitation) but does not cause a significant myocardial sodium accumulation at normal heart rates. A progressive myocardial sodium accumulation occurs only when the degree of Na+, K+-ATPase inhibition exceeds a critical magnitude.
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PMID:Cardiac Na+, K+-adenosine triphosphatase inhibition by ouabain and myocardial sodium: a computer simulation. 13 37

The bioflavonoid, quercetin, inhibited the (Na+, K+)adenosine triphosphatase purified from the electric organ of electric eel (Electrophorus electricus) or from lamb kidney. An analysis of its mode of action revealed that the formation of phosphoenzyme from Pi but not from ATP was inhibited. Quercetin increased the amount of ADP-sensitive phosphoenzyme (E1--P), indicating an inhibition of the conversion of E1--P to the ADP-insensitive form (E2--P). The rate of dephosphorylation of the phosphoenzyme formed from ATP was slowed by quercetin. These results suggest that quercetin inhibits the formation of E2--P from either Pi or E1-P as well as the hydrolysis of the phosphoenzyme. Its mode of action is therefore different from that of ouabain and other inhibitors of the Na+, K+)adenosine triphosphatase.
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PMID:Inhibition of (Na+, K+)adenosine triphosphatase and its partial reactions by quercetin. 13 69

When sarcoplasmic reticulum vesicles are exposed to trypsin for 1 min the adenosine triphosphatase (Mr = 102,000) is cleaved to fragments of Mr = 45,000 and 55,000. The purified ATPase, containing both fragments, transports Ca2+ when incorporated into vesicles containing excess phospholipid. The two fragments can only be dissociated in solutions containing 1% sodium dodecyl sulfate (SDS). Ca2+ transport activity is restored in SDS-dissociated preparations in a series of steps involving dilution with 5 volumes of 5% phospholipids in 0.75% sodium cholate, incubation in ice for 30 min, and passage through an anion exchange column. Vesicles formed in this procedure regain high Ca2+ transport activity if they are incubated in SDS solution at 24 degrees for less than 20 min. However, the extent of renaturation diminishes if the vesicles are incubated for longer periods and little acitivity is recovered in vesicles incubated longer than 60 min at 24 degrees.
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PMID:Restoration of calcium transport in the trypsin-treated (Ca+ + Mg2+)-dependent adenosine triphosphatase of sarcoplasmic reticulum exposed th sodium dodecyl sulfate. 13 48

The kinetics of K+ release from an in vitro system of rat submaxillary gland slices were studied after stimulation with parasympathomimetic secretagogues. The slices were incubated at 37degreesC in an oxygenated, enriched Krebs-Ringer bicarbonate medium in the presence and in the absence of Ca++ and of ouabain and, in some experiments, in the presence of the specific antagonists atropine (5 x 10(-6) and 2 x 10(-5) M), phentolamine (2 x 10(-5) M) or propranolol (2 x 10(-5) M. K+ release was elicited by the addition of acetylcholine (2 x 10(-5) M), pilocarpine (2 x 10(-5) M) and carbamylcholine (10(-9) to 2 x 10(-5) M). The results demonstrate that: 1) The selective stimulation of cholinergic receptors induces a rapid net release of K+ from the slices. After 10 minutes of incubation, the percent K+ released after a 2 x 10(-5) M dose of each of the three secretagogues was, respectively, 20.8%, 15.5%, and 19%. 2) The response to carbamylcholine does not occur when Ca++ is absent from the medium and is blocked by atropine but not by phentolamine or by propranolol. Atropine (5 x 10(-6) M) causes a 17-fold shift to the right on the dose-response curve to carbamylcholine. 3) The magnitude of K+ release is the ratio of two opposing mechanisms, a passive efflux and an active reuptake. The latter depends on the activity of the ouabain-sensitive Na+-K+-adenosine triphosphatase. 4) The sensitivity of the slice system to carbamylcholine seems to be greater than that to norepinephrine in terms of net K+ release after equimolar doses of 2 x 10(-5) M and also in terms of the dose required to induce a half maximal passive K+ efflux. However, the maximal passive K+ efflux is similar after both types of secretagogue and amounts of approximately 45% of the K+ present in the slices.
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PMID:Potassium release from the rat submaxillary gland in vitro. II. Induction by parasympathomimetic secretagogues. 13 10

We have examined slow changes in the rate of ATP hydrolysis for purified dog kidney Na+ and K+ stimulated adenosine triphosphatase [(Na-K)ATPase] at various concentrations of free Mg2+, Mg-ATP, K+, and Na+. The effect of these ligands on the rate of ATP hydrolysis is explained by a rapid binding step determining the initial rate of turnover followed by a slow conformational change. Inactivation of enzyme stored in the presence of ethylenediaminetetraacetic acid occurs upon adding free Mg2+, Mg-ATP, and K+; reactivation may be achieved if the concentration of these ligands is reduced. Because of the slow conformational change, the affinities for ligands affecting inactivation are time dependent. A model is presented to explain the effects of free Mg2+ and Ma-ATP on (Na-K)ATPase activity.
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PMID:A slow interconversion between active and inactive states of the (Na-K)ATPase. 13 80

In thyroidectomized rats, a single injection of L-2,,5,2'-triiodothyronine (T3) (50mug/100 g body weight) elicited at 45% increase in (Na+ + k+)-dependent adenosine triphosphatase (NaK-ATPase) activity of the membrane-rich fraction of renal cortex at the optimal time of response, 48 h after injection. Three successive doses of T3 (50 mug/100 g body weight), given on alternate days, increased NaK-ATPase by 67% in the renal cortex but had no significant effect on the outer medulla or the papilla. Moreover, T3 had no effect on Mg2+-dependent adenosine trisphatase (MgATPase) in cortex, cedulla, or papilla. Three doses of T3 (50 mug/100 g body weight) given on alternate days to thyroidectomized rats elecited a 134, 79, and 46% increase in Vmax for ATP, Na4, and K+, respectively. There were no changes in the Km for ATP or the K1/2 values for Na+ and K+. Two methods were used to estimate the effect of T3 on the number of NaK-ATPase units (assumed to represent the number of Na+ pump sites); rat renal plasma membrane fractions were incubated with [gamma-32P]ATP, Mg2+, and Na+; the 32P-labeled membrane protein yeild was quantitatively dependent on Na+ and was hydrolyzed on addition of K+. There was a linear correlation between the specific activity of NaK-ATPase (Vmax) and the amount of phosphorylated intermediate formed, in renal cortical membrane fractions from thyroidectomized rats given T3 or the diluent. There was also a linear correlation between the specific activity of NaK-ATPase (Vmax) and the amount of [3H]ouabain specifically bound (Na+-, Mg2+-, APT-dependent) to the NaK-ATPase preparation. Injection of T3 resulted in a 70% increase in NaK-ATPase activity, a 79% increase in formation of the phosphorylated intermediate, and a 65% increase in the [H]ouabain specifically bound to the NaK-ATPase system. The T3-dependent increases in Vmax for ATP, Na+, and K+ and the proportionate increases in the phosphorylated intermediate and in the amount of [3H]ouabain bound indicate that T3 increases the number of NaK-ATPase units and that this increase accounts for the increase in NaK-ATPase activity.
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PMID:Dependence of renal (Na+ + k+)-adenosine triphosphatase activity on thyroid status. 13 42

The present studies concern the roles of synthesis and degradation of the large subunit of (Na+ + k+)-adenosine triphosphatase (NaK-ATPase) in the response to triiodothyronin (T3). Single doses of either the diluent of T3 (50 mug/100 g body weight) were given to two pairs of surgically thyroidectomized rats. Twenty hours after injection, the rats received 3H- or 35S-labeled methionine administered as a constant injusion into the tail vein for 1 h. The kidneys were removed either 8 h or 20 h after infusion and the eight kidneys were divided into pairs, as follows. I, 3H (diluent)/35S (T3); II, 35S (diluent)/3H (T3); III, 3H (diluent)/35S (diluent); IV, 3H (T3)/35S (T3). Partially purified NaK-ATPase was prepared from the pooled homogenates and prepared from the pooled homogenates and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAG-electrophoresis). The large subunit of NaK-ATPase was identified by (Na+ + mg2+)-dependent and K+-sensitive incorpotation of 32P from [gamma-32P]ATP. This component had an estimated molecular weight of 92,000 and migrated as a single peptide in gels of varying total carylamide concentration, with respect to: (1) Coomassie blue staining, (b) (Na+ + Mg2+)-dependent, K+-sensitive incorporation of 32P from [gamma-32-P]ATP, and (c) T3-dependent enhanced incorporation of labeled methionine. T3 augmented incorporation of labeled methionine into the large subunit by 44% 8 h after infusion of the amino acid and by 61% 20 h after infusion. Incorporation of methionine into two adjacent polypeptides in the SDS gels was unaffected by thyroid status. The effect otical NaK-ATPase was assessed by a double label technique. Pairs of thyroidectomized rats were injected with either the diluent or 50 mug of T3/100 g body weight at 48-h after the first injection (diluent or T3, i.e. Day "zero"). Kidney cortices were processed on either Day 4 or Day 6; the partially purified NaK-ATPase fraction was prepared, labeled with [gamma-32P]ATP, and analyzed by SDS-PAG-electrophoresis. The degredation rate constants of the large subunit were similar; 0.145 and 0.124 day-1 for the hypothyroid and T3-treated groups, respectively. Thus, the T2-dependent increase in incorporation of labeled methionine into the large subunit appears to result from enhanced synthesis and this increase is sufficient to account for the entire increase in both the number of the activity of the NaK-ATPase units.
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PMID:Effect of triiodothyronine on the synthesis and degradation of renal cortical (Na+ + k+)-adenosine triphosphatase. 13 43

The purpose of this study was to measure uptake of tritiated digoxin by neoplastic tissues known to have differential contents of sodium-potassium adenosine triphosphatase (Na + K + ATPase), the presumed receptor for digoxin. Tumor samples were removed at the time of craniotomy in seven patients with meningiomas (Group 1) and seven patients with more malignant central nervous system tumors (Group 2) (three astrocytomas, three glioblastomas, one meduloblastoma). Patients with meningiomas were found to have a significantly higher digoxin uptake (21.8 +/- 7.3 ng/gm tumor versus 5.7 +/- 5.2 ng/gm tumor; (p less than 0.01) and a significantly greater tissue/serum ratio (13.9 +/- 11.7 versus 3.26 +/- 3.7, p less than 0.0). This study provides the first demonstration of increased uptake of digoxin by noncardiac pathologic tissues. The results are most likely due to differences in the number of digoxin receptor sites.
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PMID:Differential uptake of tritiated digoxin in benign and malignant central nervous system neoplasms. 13 73

Adenosine triphosphate (ATP) hydrolysis catalyzed by the plasma membrane (Na+,K+)ATPase isolated from several sources was inhibited by Mg+, provided that K+ and ATP were also present. Phosphorylation of the adenosine triphosphatase (ATPase) by ATP and by inorganic phosphate was also inhibited, as was p-nitrophenyl phosphatase activity. (Ethylenedinitrilo)tetraacetic acid (EDTA) and catecholamines protected from and reversed the inhibition of ATP hydrolysis by Mg2+, K+ and ATP. EDTA was protected by chelation of Mg2+ but catecholamines acted by some other mechanism. The specificities of various nucleotides as inhibitors (in conjunction with Mg2+ and K+) and as substrates for the (Na+, K+) ATPase were strikingly different. ATP, ADP, beta,gamma-CH2-ATP and alpha,beta-CH2-ADP were active as inhibitors, whereas inosine, cytidine, uridine, and guanosine triphosphates (ITP, CTP, UTP, and GTP) and adenosine monophosphate (AMP) were not. On the other hand, ATP and CTP were substrates and beta,gamma-NH-ATP was a competitive inhibitor of ATP hydrolysis, but not an inhibitor in conjunction with Mg2+ and K+. The Ca2+-ATPase from sarcoplasmic reticulum and F1, the Mg2+-ATPase from the inner mitochondrial membrane, were also inhibited by Mg2+. Catecholamines reversed inhibition of the Ca2+-ATPase, but not that of F1.
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PMID:Reversible inhibition of (Na+, K+) ATPase by Mg2+, adenosine triphosphate, and K+. 13 42

As enterocytes migrate from crypts to villi they differentiate and mature. To examine the effect of epithelial differentiation on ion transport we studied 22Na+ efflux and (Na+--K+)-adenosine triphosphatase activity in suspensions of epithelial cells selectively isolated from different regions of the villus to compare crypt cells with villous tip cells. Enterocytes were isolated from rat jejunum by a dilation-vibration technique. Thymidine kinase, sucrase, and alkaline phosphatase activities were measured as markers of specific cell populations. Compared to villous cells, cells from the crypt region demonstrated lower (Na"--K+)-adenosine triphosphatase activity, lower total and passive Na+ efflux rate constants, and failure of Na+ transport to respond to an actively transported nonelectrolyte.
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PMID:Na+ transport in jejunal crypt cells. 13 28


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