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 disulfonic stilbene (4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene) is found to be more potent than acetazolamide as an anion transport inhibitor in the turtle bladder, but less potent than acetazolamide as a carbonic anhydrase inhibitor. The anion-dependent (HCO-3,Cl-) moiety of the short-circuiting current is eliminated by 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene, but only after its addition to the serosal bathing fluid. Whereas 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene has no effect on Na+ transport across the bladder, it is more potent than ouabain as an inhibitor of microsomal (Na+ + K+)-ATPase of both turtle bladder and eel electric organ.
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PMID:Effects of 4-acetamido-4'-isothiocyano-2,2-disulfonic stilbene on ion transport in turtle bladders. 12 57

The rat salivary duct epithelium, which actively transports Na+, K+, and H+/HCO3- in a manner similar to renal distal tubules, was used as a model tissue to study the mechanism of action of triamterene on electrolyte transport. 10(-4) M triamterene completely blocked Na+ resorption and lowered net K+ secretion to half that of controls, whereas HCO3- accumlated in the lumen, probably due to a decrease in H+ secretion. The rates of K+ and H+/HCO3- transport in the presence of triamterene did not differ from those determined after omission of Na+ from the luminal fluid. This was considered to be evidence against a direct action of triamterene on transport of K+ and H+/HCO3-. Triamterene rapidly and reversibly reduced the transepithelial electrical potential difference. This was due to almost complete abolition of Na+ conductance of the luminal membrane at 10(-4) M triamterene, whereas K+ conductance was not altered. Triamterene, administered in vitro from the interstitial side of the isolated duct epithelium was ineffective even at the highest concentrations. The activities of the Na-K-ATPase, the Mg-ATPase and the microsomal HCO3-ATPase were influenced by 10(-4) M triameterene in a similiar fashion. These effects were clearly demonstrated only in the homogenate of the duct tissue and not in intact cells in the isolated duct preparation. Therefore they were considered unspecific. The transport studied demonstrate a primary effect of triamterene on Na+ entry from lumen to cell. Influences on net K+ and H+/HCO3 transport are secondary consequences of functional coupling between movement of Na+ and movement of K+ and H+ across the luminal cell membrane.
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PMID:On the mechanism of action of triamterene: effects on transport of Na+, K+, and H+/HCO3- -ions. 13 Feb 43

Exposure of rat brain Na+ + K+-ATPase (ATP phosphohydrolase E.C. 3.6.1.3) to concentrations of cassaine greater than 1 x 10(-4) M resulted in a poorly reversible inhibition of this enzyme. Inhibition did not require the presence of ATP and developed rapidly, but the final amount of inhibition observed was independent of time. The amount of inhibition observed at a given concentration of cassaine was reduced by increasing the concentration of membranes in the system. The inhibition of Na+ + K+-ATPase activity was associated with equivalent inhibition of the phosphorylation and (3H)-ouabain binding reactions of this enzyme, while the uninhibited enzyme was apparently kinetically normal. Concentrations of cassaine which produced this stable inhibition of Na+ + K+-ATPase had no effect on the Mg2+-activated ATPase or the NADH cytochrome-c-reductase activities of crude rat brain microsomal preparations. Cassaine inhibited the cholinesterase activity of rat brain microsomes with a Ki of about 5 x 10(-5) M, but his inhibition was fully reversible. The poorly reversible inhibitory actions of cassaine, thus, appeared specific for Na+ + K+-ATPase. Because this stable pattern of inhibition of the Na+ + K+-ATPase by cassaine required drug concentrations at least one hundred-fold greater than those which produce positive inotropic effects, it appears unlikely that this pattern of Na+ + K+-ATPase inhibition is involved in the cardiotonic actions of this drug.
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PMID:Studies on the stable inhibition of Na+ + K+-ATPase by cassaine. 13 Feb 44

The effects of ischemia on the canine myocardial (Na+ + K+)-ATPase complex were examined in terms of alterations in cardiac glycoside binding and enzymatic activity. Ability of the myocardial cell to bind tritiated ouabain in vivo was assessed after 1, 2, and 6 h of coronary occlusion followed by 45 min of reperfusion, and correlated with measurements of in vitro (Na+ + K+)-ATPase activity and in vitro [3H]ouabain binding after similar periods of ischemia. Regional blood flow alterations during occlusion and reperfusion were simultaneously determined utilizing 15 mum radioactive microspheres to determine the degree to which altered binding of ouabain might be flow related. Anterior wall infarction was produced in 34 dogs by snaring of confluent branches of the left coronary system. Epicardial electrograms delineated ischemic and border zone areas. Coronary reperfusion after 2 and 6 h of occlusion was associated with impaired reflow of blood and markedly impaired uptake of [3H]ouabain in ischemic myocardium. In both groups, in vivo [3H]ouabain binding by ischemic tissue was reduced out of proportion to the reduction in flow. Despite near-complete restoration of flow in seven dogs occluded for 1 h and reperfused, [3H]ouabain remained significantly reduced to 58 +/- 9% of nonischemic uptake in subendocardial layers of the central zone of ischemia. Thus, when coronary flow was restored to areas of myocardium rendered acutely ischemia for 1 or more hours, ischemic zones demonstrated progressively diminished ability to bind ouabain. To determine whether ischemia-induced alteration in myocardial (Na+ + K+)-ATPase might underlie these changes, (Na+ + K+)-ATPase activity and [3H]ouabain binding were measured in microsomal fractions from ischemic myocardium after 1, 2, and 6 h of coronary occlusion. In animals occluded for 6 h, (Na+ + K+)-ATPase activity was significantly reduced by 40% in epicardial and by 35% in endocardial layers compared with nonischemic myocardium. Comparable reductions in in vitro [3H]ouabain binding were also demonstrated. Reperfusion for 45 min after occlusion for 6 h resulted in no significant restoration of enzyme activity when compared to the nonreperfused animals. In six animals occluded for 2 h, a time at which myocardial creatine phosphokinase activity remains unchanged, (Na+ + K+)-ATPase activity was reduced by 25% compared with nonischemic enzyme activity. In five dogs occluded for 1 h, (Na+ + K+)-ATPase activity in ischemic myocardium was unchanged from control levels. We conclude that reduced regional myocardial blood flow, local alterations in cellular milieu, and altered glycoside-binding properties of (Na+ + K+)-ATPase all participate in the reduction of cardiac glycoside binding observed after reperfusion of ischemic myocardium. In addition, after 2 or more hours of severe ischemia, myocardial (Na+ + K+)-ATPase catalytic activity is significantly reduced despite incubation in the presence of optimal substrate concentrations.
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PMID:Ischemia-induced alterations in myocardial (Na+ + K+)-ATPase and cardiac glycoside binding. 13 Mar 83

The effect of thyroid status on QO2, QO2 (t) and NaK-ATPase activity was examined in rat skeletal muscle. QO2(t) (i.e. Na+-transport-dependent respiration) was estimated with ouabain or Na+-free media supplemented with K+. In contrast to the effects of ouabain on ion composition, intracellular K+ was maintained at about 125 meq/liter, and intracellular Na+ was almost nil in the Na+-free media. The estimates of QO2(t) were independent of the considerable differences in tissue ion concentrations. The increase in QO2(t) account for 47% of the increase in QO2 in the transition from the hypothyroid to the euthyroid state and 84% of the increase in the transition from the euthyroid to the hyperthyroid state. Surgical thyroidectomy lowered NaK-ATPase activity of the microsomal fraction (expressed per milligram protein) 32%; injections of triodothyronine (T3) increased this activity 75% in initially hypothyroid rats and 26% in initially euthyroid rats. Thyroidectomy was attended by significant falls in serum Ca and Pi concentrations. Administration of T3 resulted in further declines in serum Ca and marked increases in serum Ps concentrations. Similar effects were seen in 131I-treated rats, but the magnitude of the declines in serum Ca were less. The effects of T3 on QO2, QO2(t), and NaK-ATPase activity of skeletal muscle were indistinguishable in the 131I-ablated and surgically thyroidectomized rats. In thyroidectomized or euthyroid rats given repeated doses of T3, QO2(t) and NaA-ATPase activity increased proportionately. In thyroidectomized rats injected with single doses of T3, either 10, 50, or 250 mug/100 g body wt, QO2(t) increased linearly with NaK-ATPase activity. The kinetics of the NaK-ATPase activity was assessed with an ATP-generating system. T3 elicited a significant increase in Vmax with no change in Km for ATP.
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PMID:Thyroid thermogenesis. Relationships between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in rat skeletal muscle. 13 Mar 85

An electron microscopic study of the guinea pig myocardial cell was conducted. By the use of LaC13, two morphologically distinct tubular systems could be demonstrated. The larger one represents the transverse tubular system which originates from the plasma membrane and is continous with the extracellular space (ECS). In the heart muscle cell it forms a three-dimensional network and it closely apposed to the myofilaments at the level of the Z and I bands. A comparatively small and sparsely developed tubular system which is not accessible from the ECS represents the sarcoplasmic reticulum (SR). By means of sucrose-density centrifugation in a discontinuous gradient two main microsomal fractions were obtained (F1 and F3). The pre-existing structure of F1 could be identified as the transverse tubular system, whereas F3 originates from the SR. The morphological features (e. g., an enclosed basement membrane) and the fact that after perfusion of hearts with [3H] inulin and preparation of microsomes the ECS marker is almost completely retained in F1 indicate that upon fractionation and vesiculation inside-out vesicles are formed which trap the former extracellular fluid. Moreover, the former extracellular surface is hidden and no longer accessible for membrane-impermeable compounds. After perfusion of hearts with [3H] ouabain and fractionation and centrifugation the radioactive material was found to accumulate in F1, the kinetics being identical with that of binding to the intact tissue and with the time course of the inotropic action of ouabain. The inside-out vesicles derived from the plasma membrane are characterized by the presence of a (Na+-K+)-ATPase activity, an outward Ca pump, a high binding capacity for Ca, and a low Ca pereability. Since the (Na+-K+)-ATPase is known to react with cardiac glycosides (CG) at the outer cell surface it was not surprising to find a complete lack of inhibition of the enzyme by the membrane-impermeable CG ouabain if administered to the intact sarcolemmal microsome. After disruption of the microsomes, however, a considerable inhibition of the (Na+-K+)-ATPase became demonstrable. Similarly, the Ca permeability of the plasma membranes could only be enhanced by CG if interacting with the former outside. Although ouabain again failed to exert any action, the membrane permeable digoxin increased the Ca pereability of the intact vesicular membrane. The rate of Ca transport as an indicator of the Ca pump activity remained unaffected by CG provided from either side of the membrane. The passive Ca binding to the plasma membrane, which results in a concentration up to 5 mM in this structure, is thought to represent the Ca pool essential for excitation-contraction coupling. The CG are thought to alter the Ca binding in this pool, thus rendering depolarization more effective in releasing Ca++.
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PMID:On the sarcolemmal site of action of cardiac glycosides. 13 Jun 60

Sarcolemmal Ca++-ATPase, Mg++-ATPase, and (Na+-K+)-ATPase activities were increased in late stages of heart failure in myopathic hamsters (BIO 14.6) without any changes in the adenylate cyclase activity. On the other hand, these hamsters at early and moderate stages of heart failure showed depressions in mitochondrial calcium binding and uptake and microsomal calcium binding. Sarcolemmal (Na+-K+)-ATPase was decreased in failing hearts because of substrate lack, oxygen lack, and perfusion with Ca++-free, Na+-free, or K+-free medium. Both Mg++-ATPase and Ca++-ATPase activities of sarcolemma did not change on perfusing the hearts with substrate-free, hypoxic, Na+-free, or K+-free medium. Adenylate cyclase activity decreased on substrate-free or Ca++-free perfusion. Intracellular calcium overload produced by perfusing the hearts with medium containing calcium after Ca++-free perfusion was associated with decrease in all the sarcolemmal-bound enzyme activities. All types of failing hearts employed in this study showed a dramatic shift in the electrolyte composition. Failure of the cardiac muscle to generate contractile force on treatment with trypsin was associated with defects in the functions of sarcolemma, mitochondria, and sarcoplasmic reticulum, whereas such an effect on treatment with phospholipase C was limited to alterations in the activities of sarcolemma. The data suggest that abnormality at the level of sarcolemma plays an important role in the pathogenesis of heart dysfunction; however, the degree and direction of alterations in the sarcolemmal functions seem to be dependent upon the type of heart failure.
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PMID:Role of sarcolemmal changes in cardiac pathophysiology. 13 Jun 63

Different antiarrhythmic agents such as quinidine, procaine amide, and lodocaine at 1 mM concentrations were found to depress the ability of an isolated perfused rat heart to generate contractile force. Quinidine, but not procaine amide or lidocaine, decreased calcium uptake by both mitochondrial and microsomal fractions at different concentrations of calcium. The mitochondrial phosphorylation rate, respiratory control index, and state 3 oxygen consumption, but not ADP:O ratio and state 4 oxygen consumption, were depressed by only quinidine. None of these agents had any effect on myofibrillar Mg2+-ATPase or Ca2+-stimulated ATPase activities. On the other hand, sarcolemmal Mg2+-ATPase and Ca2+-ATPase activities, but not Na+-K+-ATPase activity, were increased by all these drugs. The sarcolemmal adenylate cyclase (EC 4.6.1.1) activity was decreased by quinidine only. These results suggest some similarities and differences in the sites of action of quinidine, procaine amide, and lidocaine within the myocardium.
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PMID:Subcellular and functional effects of quinidine, procaine amide, and lidocaine on rat myocardium. 13 Sep 65

The behavior of a Mg2+-dependent microsomal ATPase, which may be activated by Na+ and K+, was investigated in the myocardium of Guinea pigs after local irradiation. The part which can be activated by Na+ and K+ (transport-ATPase) is already slightly inhibited thirty minutes after a dose of 250 R; the inhibition rate with 1500 R amounts to about 60%, the maximal inhibition effect with a dose of 3000 R was about 70%. Four hours after a local irradiation with 1500 R, a restitution of the inhibition effect occurs with overshoot reaction; 15 and 24 hours following irradiation, a significant inhibition of the transport-ATPase activity can again be verified. The k-strophanthidine and digitoxin are inhibiting within the concentration ranges analyzed (2 X 10(-5), 2.5 X 10(-7), 5 X 10(-7) M) the activity of the transport-ATPase. The above-mentioned radiation-induced inhibition effect upon the ATPase activated by Na+ and K+ is additively increased by adding k-strophanthidine (2 X 10(-5) M) and digitoxin (2.5 X 10(-7) M).
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PMID:[Influence of roentgen rays on electrolyte changes and metabolism of the myocardium. VII. Radiation-induced inhibition of the sodium- and potassium--activated microscomal-trasport ATPase]. 13 89

A rapid mixing technique was used to follow the intermediate formation of phosphorylated enzyme and liberation of inorganic phosphate by a microsomal preparation of (Na+ + K+)-ATPase. In the presence of 100 mM Na+,but without added K+, phosphorylation reaches a constant level at a rate which is dependent on ATP concentration. Inorganic phosphate production lags during the inital phase of phosphorylation and then accumulates at a constant rate. These observations favor a scheme in which Pi is liberated as the result of turnover of the phosphorylated enzyme. In the presence of 100 mM Na+ and 2.5 mM K+ phosphate production was resolved into two phases consisting of an initial 'burst' and late steady state phase...
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PMID:Evidence for a new intermediate state in the mechanism of (Na+ + K+)-adenosine triphosphatase. 13


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