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 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 content and the properties of (Na+, K+)-ATPase in the thick ascending limb of the loop of Henle (TAL) are related to the rate and the characteristics of the transport of NaCl which has been measured in the isolated perfused cortical portion of the TAL by Burg and Green (Am. J. Physiol, 224, 659, 1973) and in the medullary portion of the TAL by Rocha and Kokko (J. Clin. Invest. 52, 612, 1973). It is concluded that the ouabain-sensitive, active transport of NaCl across the epithelium consists of primary active transport of Na and secondary active transport of Cl and that it is driven by the sodium pump or (Na+, K+)-ATPase.
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PMID:The function of (Na+, K+)-ATPase in the thick ascending limb of Henles loop. 13

In order to differentiate whether activation of NaK-ATPase in thyroid thermogenesis is due to increased numbers of active 'sodium pump' units or due to a change in the kinetics of the enzyme, the effect of T3 on activation energy (Ea) of NaK-ATPase was determined in rat liver, kidney and brain. Injection of T3 produced significant increases in the specific activity of NaK-ATPase in liver and kidney but not in brain homogenates. T3 injections produced no significant change in the Ea of NaK-ATPase in any of the three tissues. The data are compatible with the hypothesis that thyroid stimulation of the sodium pump is brought about by an increase in the number of active pump units.
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PMID:Lack of thyroid hormone effect on activation energy of NaK-ATPase. 13 10

Various estimations of the erythrocyte sodium pump were determined in 18 female and 11 male adult subjects. In the female group, but not in the male group, the sodium concentration increased with age; the erythrocyte active transport decreased and passive transport increased with age and could account for the observed change in erythrocyte sodium concentration with age. The erythrocyte Na-K ATPase decreased with age in the females and this could account for the observed change in active transport.
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PMID:Changes in the erythrocyte sodium pump with age. 13 13

Catecholamine (CA) release was studied in rat adrenal incubated in vitro. Inhibition of (Na + K)-ATPase either by omission of K+ from the incubation medium or by addition of a high concentration of ouabain (10(-3) M) caused increased release of CA from the adrenal. Diphenylhydantoin (DPH) (10(-5) M) inhibited the spontaneous as well as the acetylcholine (10(-4) M)-induced release of CA. However, in K+-free medium or in the presence of 10(-3) M ouabain, DPH had no significant effect on CA release. A low concentration of ouabain (10(-10) M) caused a significant inhibition of spontaneous and of acetylcholine-induced release of CA. In a K+-free medium ouabain (10(-10) M) had no effect on CA release. DPH (10(-5) M) and a low concentration of ouabain (10(-10) M) caused a significant activation of (Na + K)-ATPase in a membrane fraction of the adrenal medulla. It is suggested that DPH and low ouabain concentrations inhibit CA release from the adrenal by activation of the sodium pump. The possible mechanism involved is discussed.
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PMID:Mechanism of inhibition of catecholamine release from adrenal medulla by diphenylhydantoin and by low concentration of ouabain (10(-10) M). 13 99

Inside-out membrane vesicles of human red cells, prepared according to the method of Steck et al. (1970) Science 168, 255-257) have sufficiently low cation permeability to allow the examination of the side-specific interactions of ligands with the asymmetric sodium pump complex. In accordance with the known properties of the pump in intact cells the following results were observed: (a) ATP-dependent sodium influx and (b) maximal (sodium, potassium)-ATPase with K+ present inside the vesicles with larger than or equal to 20 micronM ATP. With much lower [ATP], K+ inhibited sodium-activated ATPase. K+ was inhibitory at either surface. Inhibition was different on the two sides since cytoplasmic (extravesicular) Na+ counteracted inhibition by cytoplasmic (extravesicular) K+ but not inhibition by K+ at the plasma or external membrane surface, i.e. intravesicular K+. A decrease in the steady state level of the phosphenzyme intermediate of sodium-activated ATPase was caused also by K+ at either surface. The effect of cytoplasmic K+ is compatible with its competitive inhibition of activation of phosphorylation of the enzyme by cytoplasmic Na+. At 37 degrees, the inhibitory effect of external K+ is due to interaction with the phosphoenzyme to form a stable complex of K+ with the dephosphenzyme resulting in a decreased overall reaction rate but increased turnover of the phosphoenzyme (E-P + K leads to EK + Pi). At 0 degree, external K+ inhibits by interacting with the unphosphorylated enzyme to form an occluded enzyme-K complex. This results in a decreased overall rate but relatively small change in apparent turnover of the phosphoenzyme. At 0 degree, but not at 37 degrees, external Na+ counteracted the inhibitory effects of external K+.
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PMID:Sidedness of (sodium, potassium)-adenosine triphosphate of inside-out red cell membrane vesicles. Interactions with potassium. 14 Jan 67

Experiments were performed to investigate whether the inhibitory effect of ethanol on intestinal glucose transport is related to its action on the brush border or on the ATPase-dependent sodium pump of the basolateral membrane of the enterocyte. We compared the effect of ethanol on glucose and water transport when it was added either to the mucosal or to the serosal solution of an in vitro preparation of hamster jejunum. The purpose of the addition of ethanol to the serosal solution was to mimic a situation similar to that produced when ouabain is placed on the serosal side to inhibit the ATPase-dependent sodium pump at the basolateral membrane. The presence of 450 mM ethanol (2.07%) in the mucosal solution depressed glucose and water transport by 40 and 63%, respectively, but the presence of the same concentration of ethanol on the serosal side had no effect on glucose and water absorption. These findings seem to indicate that the depressing effect of ethanol on intestinal glucose and water transport cannot be ascribed to the inhibition of the Na+, K+-sensitive ATPase-dependent sodium pump located at the basolateral membrane.
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PMID:On the mechanism of the inhibitory effect of ethanol on intestinal glucose and water absorption. 14 Dec 6

The effects of iontophoretically applied Na+-, K+-dependent adenosinetriphosphatase (Na+,K+-ATPase) (EC 3.6.1.3) inhibitors (ouabain, digitoxin, digitoxigenin, strophanthin K, strophanthidin, thevetin A and B, ethacrynate, and harmaline) on the depression of rat cerebral cortical neurones by noradrenaline, 5-hydroxytryptamine, and histamine have been studied. The inhibitors antagonized depressions of spontaneously active neurones evoked by these amines, but not those evoked by gamma-aminobutyric acid, adenosine, adenosine 5'-monophosphate, or calcium. The antagonistic potencies of the various inhibitors appeared to be proportional to their known potencies as inhibitors of Na+, K+-ATPase. The data therefore support the hypothesis that amines depress central neurones by activating an electrogenic sodium pump.
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PMID:Antagonism of biogenic amine-induced depression of cerebral cortical neurones by Na+, K+-ATPase in inhibitors. 14 20

The amines noradrenaline, dopamine, 5-hydroxytryptamine, and histamine (0.01-0.5 mM) enhanced the activity of Na-K-ATPase (EC 3.6.1.3) in rat cerebral cortical synaptosomal fractions. The activities of Mg-ATPase and Ca-Mg-ATPase were not significantly affected. No stimulation of Na-K-ATPase occurred in the presence of chelating agents (0.5 mM EGTA or EDTA) unless 0.5 mM calcium had also been added to the incubation medium. These results are consistent with the hypothesis that amines depress cerebral cortical neurones by activation of an electrogenic sodium pump. Calcium ions appear to be involved in this process.
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PMID:Stimulation of cerebral cortical synaptosomal Na-K-ATPase by biogenic amines. 14 37

1. The activation by Na ions and the effect of the anti-L antibody on the sodium pump of low-potassium type (LK) erythrocytes, have been studied by measuring ouabain-sensitive ATPase activity of red cell membranes of LK goats. The experimental data were first corrected for incomplete occupation of the external K sites of the pump, using a saturation function obtained from influx experiments.2. Double-reciprocal plots of the corrected rates against Na concentration at various fixed K concentrations, yield a pattern of competitive K inhibition when it is assumed that three equivalent sodium sites take part in the internal activation of LK-(Na+K)-ATPase. The dissociation constant of Na at each site (K(m)) lies between 10 and 20 mM and that of K as competitive inhibitor (K(i)), between 1.5 and 4.5 mM.3. The maximal rate of hydrolysis of LK goat (Na + K)-ATPase is not different from those usually obtained with the high-potassium type (HK) red cell enzyme. Then, the low pumping rate of LK erythrocytes in physiological conditions is only reflecting the poor Na affinity, both absolute and relative, at the internal Na sites of their sodium pumps.4. The stimulation of the ouabain-sensitive ATPase activity by sensitization of the membranes with anti-L serum, is mediated by a threefold reduction of the K(m)/K(i) ratio at each site. K(m) decreases by a factor of 10, but there is also a smaller diminution of K(i). The maximal rate of hydrolysis, however, is unchanged by the anti-L treatment. The least-squares fitting of the pooled data by the rate equation, converges better with less than three and more than two equivalent sodium sites.5. The affinity sequence at two external K sites of the LK goat erythrocyte sodium pump, determined in the presence of 100 mM external Na, is Rb > K > Cs. It is obtained from the concentration dependence in influx experiments, and is the same as reported for human red cells.6. Cubic-root Dixon plots of the corrected ouabain-sensitive ATPase activity against the concentration of K and its congeners, show the sequence Tl > K > Rb > Na > Cs for the affinities at the internal cation sites of the LK sodium pump. Anti-L treatment decreases the relative magnitude of Na and Cs selectivities, it being not certain whether a Rb-Na transition then occurs.7. The results are discussed in terms of possible mechanisms whereby the sodium pump of LK and HK red cells may adjust the properties of their cation sites upon translocation of monovalent cations.
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PMID:The interaction of monovalent cations with the sodium pump of low-potassium goat erythrocytes. 14 81


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