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)

Intraperitoneal administration of a single dose (6 mg/kg body wt.) of mercuric chloride led to a rapid and irreversible inhibition of Na+/K(+)-ATPase activity in rat cerebral capillaries. The activity measured at 1 h, 18 h and 5 days after injection was, respectively, 53, 44 and 26% of the control. By contrast, Mg(2+)-ATPase activity in the capillaries remained uninhibited throughout the observation period. Mercuric chloride administration did not affect either of the two enzyme activities in nerve endings, which is consistent with the inability of the compound to penetrate the blood-brain barrier. The mercuric-chloride-induced impairment of the capillary sodium pump may contribute to disturbances of ion homeostasis in the brain and thus to the neurophysiological abnormalities accompanying this exposure. Direct treatment of the isolated cerebral capillary preparations with mercuric chloride evoked a stronger inhibitory effect on Mg(2+)-ATPase (IC50 = 0.25 microM) than on Na+/K(+)-ATPase (IC50 = 5.0 microM). This result indicates that the effect in vivo may not have resulted from direct interaction of the compound with the latter enzyme.
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PMID:Durable inhibition of rat cerebral capillary Na+/K(+)-ATPase after in vivo administration of mercuric chloride. 166 49

Triorganotins have been reported to affect heme metabolism as well as the cardiovascular system. Our recent studies indicated that these organotins inhibit cardiac sarcoplasmic reticulum Ca(2+)-transport and cAMP-stimulated phosphorylation of specific proteins involved in Ca2+ transport, suggesting their interference with cardiac adrenergic function. The present study determines the effect of three organotins--tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT)--on rat cardiac ATPases and catecholamine binding, since these phenomena are involved in cardiac function. Cardiac membrane fraction was prepared from heart ventricles of male Sprague-Dawley rats. All three organotins inhibited cardiac Na+,K(+)-ATPase, [3H]ouabain binding, K(+)-activated p-nitrophenyl phosphatase (K(+)-PNPPase) and oligomycin-sensitive (OS) and oligomycin-insensitive (OI) Mg(2+)-ATPase in a concentration-dependent manner. K(+)-PNPPase was less sensitive to these triorganotins when compared to Na+K(+)-ATPase, suggesting that triorganotins affect the Na(+)-pump activity by acting on the Na(+)-dependent phosphorylation process. OS Mg(2+)-ATPase was more sensitive to these organotins when compared to OI Mg(2+)-ATPase, confirming their potent effect on the enzymes of oxidative phosphorylation. The order of potency is TBT greater than TET greater than TMT. TET and TMT, but not TBT, inhibited [3H]norepinephrine and [3H]dopamine binding to cardiac membranes in a concentration-dependent manner, the effect being more with TET. These results suggest that triorganotins inhibit sodium pump activity as well as ATP synthesis. Since Na+,K(+)-ATPase is involved in the active transport of catecholamines, triorganotins not only inhibited the catecholamine transport but also to some extent affected catecholamine binding, thus interfering with cardiac function.
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PMID:Triorganotin inhibition of rat cardiac adenosine triphosphatases and catecholamine binding. 166 43

The activity and properties of Na,K-ATPase in erythrocytes and their membrane preparations (ghosts) from 34 subjects with borderline hypertension and 21 normotensive controls were studied. The Na,K-ATPase activity was found to be by 43% lower as compared to control group. No changes in the Na,K-ATPase activity were revealed in the ghosts of borderline subjects. This suggests that the plasma of borderline subjects contains an inhibitor of Na,K-ATPase. The plasma level of sodium pump inhibitor was measured in 21 borderline hypertensive subjects. It was found to be about 19% compared with the control group. These findings suggest presence of Na,K-ATPase inhibitor in the plasma of borderline subjects, which is likely to be involved in the development of hypertension.
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PMID:[The activity and properties of Na,K-ATPase in the erythrocytes and the Na-pump inhibitor in the plasma of subjects with borderline arterial hypertension]. 166 9

Effect of neurotoxins veratrine (100 micrograms/ml) and tetrodotoxin (1 microM) on the binding of 3H-ouabain (10(-8) M) with Na,K-ATPase of intact synaptosomes and isolated synaptic membranes was studied. The persistent opening of sodium channels in synaptosomes by veratrine results in an increase of specific binding of the labeled ligand by 20%. A similar effect was caused by Na/H exchanger monensin. Destruction of microtubules with vinblastine and colchicine has no influence on veratrine action, while depolymerization of microfilaments with cytochalasin B reverses the neurotoxin effect. In isolated synaptic membranes veratrine and tetrodotoxin stimulate ouabain binding, the absolute veratrine-induced increment being several times higher in the presence of ATP than in its absence. Since the closed vesicles of any type are not permeable to ATP and ouabain, it means that in the isolated membranes an interaction between sodium channels and Na,K-ATPase molecules takes place. In intact nerve endings such a mechanism may be operative along with the known ways of control of sodium pump and its ouabain-binding site.
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PMID:[The coupling of Na,K-ATPase with the sodium channels in the plasma membranes of the brain synaptosomes of rats]. 166 53

Natriuretic hormone is a digoxin-like substance that inhibits Na-K-ATPase, membraneous sodium pump, leads to storage of sodium in the cells, increases their tone which plays a key role in the increase of peripheral resistance of the blood vessels and progression of hypertensive disease. Results indicate that the level of natriuretic hormone was increased at all stages of hypertensive disease, positively correlated with aldosterone and kallikrein and negatively--with the plasma renin activity that confirms its pressor action.
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PMID:[The role of the natriuretic hormone in neurohumoral regulation in hypertension]. 168 83

The expression of the (Na+ + K+)-ATPase in cultured chicken skeletal muscle can be altered by varying the demand for ion transport. Veratridine, an activator of voltage-sensitive Na+ channels, causes a specific transient increase in biosynthesis of the sodium pump that accounts for the doubling of the number of (Na+ + K+)-ATPase molecules in the sarcolemma (Wolitzky, B.A., and Fambrough, D.M. (1986) J. Biol. Chem. 261, 9990-9999). Here we report a study of veratridine-induced up-regulation, focusing upon alpha- and beta-mRNA levels and transcription rates. Myotubes normally express the alpha 1-isoform mRNA and the beta-mRNA at a molar ratio of 0.6 +/- 0.1 (S.D.). In the presence of veratridine, the beta-mRNA is transiently up-regulated approximately 3-fold. The kinetics of this increase parallel the rate of beta-subunit protein synthesis. The increase in beta-mRNA during up-regulation is accomplished by an increase in the transcription rate of the beta gene. The veratridine-induced increase in beta-mRNA is not blocked by cycloheximide. The alpha-mRNA also increases during exposure to veratridine, but this increase is very modest and occurs very late in the up-regulation process. The increased beta-mRNA results in over-production of beta-subunits, which we postulate drives more efficient assembly of alpha beta complexes, i.e. sodium pump molecules. As the up-regulated state is achieved the level of beta-mRNA falls abruptly, reflecting a marked decrease in beta-mRNA stability. Treatment of up-regulated myotubes with tetrodotoxin, a veratridine antagonist, results in rapid down-regulation of the sodium pump, while having little or no effect on the levels of alpha 1- and beta-mRNAs.
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PMID:Pre-translational regulation of the (Na+ + K+)-ATPase in response to demand for ion transport in cultured chicken skeletal muscle. 168 13

Inactivation of Na+/K(+)-ATPase activity by the MgPO4 complex analogue Co(NH3)4PO4 leads, in everted red blood cell vesicles, to the parallel inactivation of 22Na+/K+ flux and 86Rb/Rb+ exchange, but leaves the 22Na+/Na(+)-exchange activity and the uncoupled ATP-supported 22Na+ transport unaffected. Furthermore, inactivation of purified Na+/K(+)-ATPase by Co(NH3)4PO4 leads to a parallel decrease of the capacity of the [3H]ouabain receptor site, when binding was studied by the Mg2+/Pi-supported pathway (ouabain-enzyme complex II) but the capacity of the ouabain receptor site was unaltered, when the Na+/Mg2+/ATP-supported pathway (ouabain-enzyme complex I) was used. No change in the dissociation constants of either ouabain receptor complex was observed following inactivation of Na+/K(+)-ATPase. When eosin was used as a marker for the high-affinity ATP-binding site of the E1 conformation, formation of stable E'2.Co(NH3)4PO4 complex led to a shift in the high-affinity ATP-binding site towards the sodium form. This led to an increase in the dissociation constant of the enzyme complex with K+, from 1.4 mM with the unmodified enzyme to 280 mM with the Co(NH3)4PO4-inactivated enzyme. It was concluded, that the effects of Co(NH3)4PO4 on the partial activities of the sodium pump are difficult to reconcile with an alpha, beta-protomeric enzyme working according the Albers-Post scheme. The data are consistent with an alpha 2, beta 2 diprotomeric enzyme of interacting catalytic subunits working with a modified version of the Albers-Post model.
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PMID:Blocking of Na+/K+ transport by the MgPO4 complex analogue Co(NH3)4PO4 leaves the Na+/Na(+)-exchange reaction of the sodium pump unaltered and shifts its high-affinity ATP-binding site to a Na(+)-like form. 169 57

Previous studies from our laboratory have indicated that chlordecone (Kepone CD), an organochlorine insecticide, inhibited cardiac sodium pump activity and catecholamine uptake suggesting that CD may interfere with cardiac function. Sarcoplasmic reticulum (SR) calcium pump has an important role in myocardial contraction and relaxation, besides Na+ transport. Since CD interferes with cardiac Na+ ion translocases, we have studied CD effects on cardiac SR calcium pump activity. Experiments were carried out both in vitro and in vivo. SR was isolated from heart ventricles of male Sprague-Dawley rats. Cardiac SR Ca2(+)-ATPase. 45Ca-uptake and cAMP as well as calmodulin (CaM) dependent protein phosphorylation were measured. Ca2(+)-ATPase was differentiated into low affinity and high affinity forms by measuring the activity using 50 and 0.7 microM free Ca2(+)-respectively. CD in vitro inhibited 45Ca-uptake by SR in a concentration dependent manner with an IC50 value of 7 microM and SR 45Ca-uptake was totally inhibited at 20-30 microM CD. In agreement with this, both high affinity and low affinity Ca2(+)-ATPases, which are involved in Ca2+ transport across membranes, were also inhibited by CD in a concentration dependent manner with IC50 values of 0.7 and 3.2 microM respectively. Both Ca2(+)-ATPase and 45Ca-uptake by cardiac SR were significantly lower in rats treated with CD (25, 50 or 75 mg/kg) when compared to control rats. cAMP as well as CaM significantly elevated the 32P-binding to SR proteins in vitro to about 70-80%. In the presence of CD, this 32P-binding was reduced, however, not concentration dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of chlordecone (Kepone) on calcium transport mechanisms in rat heart sarcoplasmic reticulum. 170 52

Chick pineal cells in static culture display a persistent photosensitive circadian rhythm of melatonin production and release. Pulses of white light or darkness, in otherwise constant red light, induce phase shifts in subsequent cycles whose magnitude and direction depend on the phase at which the pulse is given. Such "phase-dependent phase shifts" are mediated by effects on the underlying pacemaker. We reported previously that inhibiting the Na-K-ATPase with ouabain or salt solutions lacking potassium evokes phase shifts with the same phase dependence as those induced by pulses of darkness. One of the consequences of inhibiting the sodium pump is cell swelling. To test the relevance of this effect, we exposed chick pineal cells to pulses of medium containing reduced concentrations of NaCl, which should cause cell swelling. These hypotonic solutions induced phase shifts in the melatonin rhythm with the same phase dependence as those caused by pulses of ouabain or darkness. The size of the phase shifts varied with degree of dilution, and phase shifting was prevented by replacement of NaCl. In view of previous results showing that hypertonic media mimicked the phase-shifting effects of light, these results suggest that cell swelling may mediate the darklike effects of ouabain on the circadian pacemaker in chick pineal cells.
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PMID:Low salt mimics effects of dark pulses on circadian pacemaker in cultured chick pineal cells. 175 May 67

Cardiac Na+,K(+)-ATPase, the receptor molecule for digitalis glycosides, have isoforms with different intrinsic affinities for the glycosides. Expression of these isoforms are under developmental and hormonal regulation. Switching in isoforms to those with lower intrinsic affinity may decrease digitalis sensitivity of the heart. In addition to the intrinsic affinity of the cardiac Na+,K(+)-ATPase for the glycoside, increases in the rate of Na+ influx and decreases in extracellular K+ concentrations increase glycoside sensitivity of the heart and also reduces the margin of safety by reducing reserve capacity of the sodium pump. Reserve capacity of the sodium pump is also reduced by pathological conditions or aging, resulting in reduced margin of safety for the glycoside. Events that follow sodium pump inhibition also affect sensitivity of the heart to digitalis toxicity. These are hypercalcemia and magnesium depletion. It is now feasible to predict digitalis sensitivity of the heart, not empirically but based on the understanding of the mechanisms responsible for the positive inotropic and toxic actions of the glycoside.
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PMID:Digitalis sensitivity of Na+,K(+)-ATPase, myocytes and the heart. 184 28


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