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)

Recent studies have revealed that the action of the proton-translocating ATPase of the plasma membrane of yeast is an important determinant of several stress tolerances and affects the capacity of cells to synthesise heat shock proteins in response to heat shock [Panaretou, B. & Piper, P. W. (1990) J. Gen. Microbiol. 136, 1763-1770; Coote, P. J., Cole, M. B. & Jones, M. V. (1991) J. Gen. Microbiol. 137, 1701-1708]. This study investigated the changes to the protein composition of the Saccharomyces cerevisiae plasma membrane that result from a heat shock to dividing cultures and the entry to stationary growth caused by carbon source limitation. Plasma membranes were prepared from exponential, heat-shocked and stationary yeast cultures. The proteins of these membrane preparations were then analysed by polyacrylamide gel electrophoresis and immunoblot measurement of ATPase levels. The protein composition of plasma membranes displayed two prominent changes in response to both heat shock and the entry to stationary phase: (a) a reduction in the level of the plasma membrane ATPase; and (b) the acquisition of a previously uncharacterised 30 kDa heat-shock protein (hsp30). The ATPase decline with heat shock probably exerts an important influence over the ability of the cell to maintain ATPase activity, and therefore intracellular pH, during extended periods of stress. Through in vivo pulse-labelling of plasma membrane proteins synthesised before and during heat shock, followed by subcellular fractionation, it was shown that hsp30 is the only protein induced by the yeast heat-shock response that substantially copurifies with plasma membranes. It might therefore exert a stress-protective function specifically at this membrane.
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PMID:The plasma membrane of yeast acquires a novel heat-shock protein (hsp30) and displays a decline in proton-pumping ATPase levels in response to both heat shock and the entry to stationary phase. 153 43

1. Experiments were designed to determine the effect of inhibition of Na+, K+ ATPase by ouabain, Na(+)-free and K(+)-free solutions on the relaxations induced by nitric oxide, nitroglycerin and sodium nitroprusside in coronary smooth muscle. 2. Rings without endothelium of canine left anterior descending coronary artery were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution, in the presence of indomethacin, propranolol, and phenoxybenzamine. The rings were incubated with ouabain, Na(+)-free or K(+)-free solutions prior to contractions with prostaglandin F2 alpha. 3. Nitric oxide induced transient relaxations which were significantly depressed by ouabain but were not affected by Na(+)- or K(+)-free solutions. Thus, the inhibitory effect of ouabain on relaxations to nitric oxide is not due to inhibition of the Na+, K+ pump. 4. The relaxation induced by sodium nitroprusside was impaired both in the presence of ouabain and after incubation in Na(+)- or K(+)-free solution, suggesting that it may involve in part activation of Na+, K+ pumping. 5. Only high concentration of ouabain and Na(+)-free solution decreased the relaxation evoked by nitroglycerin, indicating that the mechanism of action of nitroglycerin on vascular smooth muscle does not involve the Na(+)-K+ pump.
Gen Pharmacol 1991
PMID:Ouabain, Na(+)-free and K(+)-free solutions and relaxations to nitric oxide and nitrovasodilators. 164 45

1. The effects of three class 1 antiarrhythmic drugs procainamide (class 1A) tocainide (class 1B) and lorcainide (class 1C) on microsomal Na(+)-K(+)-ATPase activity were compared with those of ouabain in guinea pig heart preparations. 2. All three antiarrhythmic drugs exhibited concentration-dependent inhibitory actions on the enzyme activity in a fashion similar to that of ouabain. 3. The rank order of their potencies showed the following tendency: lorcainide much greater than tocainide greater than procainamide. However, while the actions of lorcainide were comparable to those of cardiotonic steroids, those of procainamide became significant only at concentrations above 80 microM. 4. The IC50 values were 1.8 +/- 0.5 microM for ouabain, 14.6 +/- 3.4 microM for lorcainide, 2.8 +/- 0.7 mM for tocainide and 6.7 +/- 1.1 mM for procainamide. 5. The results demonstrate that these antiarrhythmic agents inhibit the ouabain-sensitive myocardial Na(+)-K(+)-ATPase activity in vitro with comparatively varying potencies. 6. These interactions may be pertinent to the proarrhythmic or arrhythmogenic effects of the class 1 type of antiarrhythmic drugs.
Gen Pharmacol 1991
PMID:Comparative effects of procainamide, tocainide and lorcainide on Na(+)-K(+)-ATPase in guinea pig heart preparations. 164 50

We have compared the response of proton and water transport to oxytocin treatment in isolated frog skin and urinary bladder epithelia to provide further insights into the nature of water flow and H+ flux across individual apical and basolateral cell membranes. In isolated spontaneous sodium-transporting frog skin epithelia, lowering the pH of the apical solution from 7.4 to 6.4, 5.5, or 4.5 produced a fall in pHi in principal cells which was completely blocked by amiloride (50 microM), indicating that apical Na+ channels are permeable to protons. When sodium transport was blocked by amiloride, the H+ permeability of the apical membranes of principal cells was negligible but increased dramatically after treatment with antidiuretic hormone (ADH). In the latter condition, lowering the pH of the apical solution caused a voltage-dependent intracellular acidification, accompanied by membrane depolarization, and an increase in membrane conductance and transepithelial current. These effects were inhibited by adding Hg2+ (100 microM) or dicyclohexylcarbodiimide (DCCD, 10(-5) M) to the apical bath. Net titratable H+ flux across frog skin was increased from 30 +/- 8 to 115 +/- 18 neq.h-1.cm-2 (n = 8) after oxytocin treatment (at apical pH 5.5 and serosal pH 7.4) and was completely inhibited by DCCD (10(-5) M). The basolateral membranes of the principal cells in frog skin epithelium were found to be spontaneously permeable to H+ and passive electrogenic H+ transport across this membrane was not affected by oxytocin. Lowering the pH of the basolateral bathing solution (pHb) produced an intracellular acidification and membrane depolarization (and an increase in conductance when the normal dominant K+ conductance of this membrane was abolished by Ba2+ 1 mM). These effects of low pHb were blocked by micromolar concentrations of heavy metals (Zn2+, Ni2+, Co2+, Cd2+, and Hg2+). Lowering pHb in the presence of oxytocin (50 mU/ml) produced a transepithelial current (3 microA.cm-2 at pHb 5.5) which was blocked by 100 microM of Hg2+, Zn2+, or Ni2+ at the basolateral side, and by DCCD (10(-5) M) or Hg2+ (100 microM) from the apical side. The net hydroosmotic water flux (JH2O) induced by oxytocin in frog bladder sacs was blocked by inhibitors of H(+)-adenosine triphosphatase (ATPase). Diethylstilbestrol (DES 10(-5) M), oligomycin (10(-8) M), and DCCD (10(-5) M) prevented JH2O when present in the lumen. These effects cannot be attributed to inhibition of metabolism since cyanide (10(-4) M), or 2-deoxyglucose (10(-3) M) had no effect on JH2O.(ABSTRACT TRUNCATED AT 400 WORDS)
J Gen Physiol 1991 Apr
PMID:Common channels for water and protons at apical and basolateral cell membranes of frog skin and urinary bladder epithelia. Effects of oxytocin, heavy metals, and inhibitors of H(+)-adenosine triphosphatase. 164 38

Denervated fast-twitch rabbit muscles were progressively losing their fresh weight and the yield of sarcotubular protein was increasing. The activity of Ca(2+)-ATPase was affected but very slightly, the basal Mg(2+)-ATPase and the Mg(2+)-ATPase/Ca(2+)-ATPase ratio however increased together with a simultaneous depression of the membrane-bound acetylcholinesterase activity. We did not observe any differences in density properties of sarcotubular fractions between control and denervated muscle. However, a relative enrichment in SM and H fraction could be seen after denervation with small changes in the content of the Ca(2+)-pump protein, increased levels of calsequestrin and cholesterol, mostly in the heavy and the SM fraction. After denervation the binding sites for 3H-PN-200-110 did not show any changes in receptor affinity, but the number of putative Ca(2+)-channels increased twice along with a depression of 3H-ouabain binding sites. We suggest that the denervation of fast-twitch muscle leads to the hypertrophy of the junctional sarcoplasmic reticulum and the T-system. Changes in the cholesterol content, in the number of putative Ca(2+)-channels and in Na+, K(+)-ATPase can affect the muscle contraction.
Gen Physiol Biophys 1991 Apr
PMID:Effects of denervation on the contents of cholesterol and membrane systems involved in muscle contraction in rabbit fast-twitch sarcotubular system. 165 Jul 29

The membrane potential responsiveness of human myeloid leukemia cells (ML-1 line) was studied with the voltage sensitive fluorescent dye diS-C3-(5). The experimental procedure used in this study enabled us to assess the magnitude of the membrane potential change in cells treated with ouabain, 12-0-tetradecanoylphorbol-13-acetate (TPA) and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), relative to the membrane potential in the untreated control. Inhibition of the Na, K-ATPase by ouabain was followed by a (20 +/- 4) mV depolarization. In undifferentiated homogeneous cell population TPA caused a (19.4 +/- 4.4) mV depolarization while FMLP had virtually no effect. Cells in which granulocytic or monocytic differentiation was induced by retinoic acid or 1,25-dihydroxyvitamin D3 exhibited under the effect of TPA a (57.8 +/- 7.1) mV and (34.8 +/- 10.9) mV depolarization, respectively. A very small transient depolarization was also observed up on treating of the cells with FMLP. The changes in the membrane potential responsiveness in the induced cells are obviously connected with the cell differentiation.
Gen Physiol Biophys 1991 Feb
PMID:Membrane potential in human myeloid leukemia cell line ML-1: responsiveness of granulocytic and monocytic differentiated cells. 165 Dec 72

The present article is concerned with the oligomeric structure and function of the Na,K-pump (Na,K-ATPase). The questions we have addressed, using radiation inactivation and target size analysis as well as ligand binding, are whether the minimal structural unit and the functional unit have more than one molecule of the catalytic subunit, alpha. We first discuss the fundamentals of the radiation inactivation method and emphasize the necessity for rigorous internal standardization with enzymes of known molecular mass. We then demonstrate that the radiation inactivation of Na,K-ATPase is a stepwise process which leads to intermediary fragments of the alpha-subunit with partial catalytic activity. From the target size analysis it is most likely that the membrane-bound Na,K-ATPase is structurally organized as a diprotomer containing two alpha-subunits. Determination of ADP- and ouabain-binding site stoichiometry favors a theory with one substrate site per (alpha beta)2.
Soc Gen Physiol Ser 1991
PMID:Functional significance of the oligomeric structure of the Na,K-pump from radiation inactivation and ligand binding. 165 78

Kinetic investigations carried out in a number of laboratories have accumulated evidence favoring modification of the Albers-Post mechanism. The results of the rapid mixing studies involving the eel enzyme indicate that the complex kinetic behavior is confined to the Na(+)-activated reaction pathway (Na-ATPase). The main conceptual problem in interpreting the dephosphorylation experiments involves the intermediate component, which turns over too slowly to account for the overall velocity of Pi production in the presence of Na+ and K+ and exhibits behavior compatible with an ADP-insensitive phosphoenzyme. Attempts to simulate the dephosphorylation reaction using schemes in which the intermediate component represents a precursor to the K(+)-sensitive phosphoenzyme, E2P, were unsuccessful in reproducing both the pre-steady-state and steady-state time dependence. When Na+ and K+ were both present during phosphorylation, the time course of dephosphorylation showed no evidence of an intermediate decay component, implying that K+ either prevents its formation or accelerates its turnover. Complex kinetic behavior was also observed in the phosphorylation reaction under conditions where the reaction was initiated by the simultaneous addition of ATP, Na+, and Mg2+. Preincubation with Na+ eliminated the biexponential pattern of accumulation so that only the fast phase was seen. The proportion of EP in the slow phase of phosphorylation was approximately equal to the fraction of EP in the intermediate phase of dephosphorylation (roughly one-third of the sites), suggesting that the two may be related to the same catalytic activity. To try to explain these observations using recent modifications to the Albers-Post mechanism is difficult without invoking additional complex effects of the transported ions. We propose that a series model for phosphorylation is inadequate and that further modification of the mechanism is required. The alternative to a consecutive mechanism is a parallel pathway scheme: [sequence: see text] In this model the enzyme exists in two distinct forms which are distributed in the upper and lower pathways in a ratio of 2:1. In the lower pathway the rates of phosphorylation and E2P hydrolysis are controlled by the kinetics of ligand binding because of a structural constraint (ion channel?) imposed by the transport protein. When phosphorylation is carried out in the presence of Na+ alone, E2P and E2P' accumulates rapidly and give rise to the fast and intermediate components of dephosphorylation, respectively. Preincubation with Na+ and K+ eliminates the functional differences between these pathways by removing the kinetic dependence of ligand binding, resulting in behavior that conforms to the Albers-Post mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)
Soc Gen Physiol Ser 1991
PMID:The partial reactions of the Na(+)- and Na(+) + K(+)-activated adenosine triphosphatases. 165 82

The pioneering work on the Na,K-ATPase was dominated by the concept that this enzyme was essentially the same in all tissues and organisms. Now, with the development of new molecular and immunological techniques, the Na,K-ATPase is found to be composed of several clearly different subunit types. This brief update focuses on the identification of subunits and recent ideas about their functional differences.
Soc Gen Physiol Ser 1991
PMID:Overview: subunit diversity in the Na,K-ATPase. 165 94

Vectorial function of polarized transporting epithelia requires the establishment and maintenance of a nonrandom distribution of Na,K-ATPase on the cell surface. In many epithelia, the Na,K-ATPase is located at the basal-lateral domain of the plasma membrane. The mechanisms involved in the spatial organization of the Na,K-ATPase in these cells are poorly understood. We have been investigating the roles of regulated cell-cell contacts and assembly of the membrane-cytoskeleton in the development of the cell surface polarity of Na,K-ATPase. We have shown that the Na,K-ATPase colocalizes with distinct components of the membrane-cytoskeleton in polarized Madin-Darby canine kidney (MDCK) epithelial cells. Significantly, we showed directly that Na,K-ATPase is a high affinity binding site for the membrane-cytoskeletal proteins ankyrin and fodrin, and that all three proteins exist in a high molecular weight protein complex that also contains the cell adhesion molecule (CAM) uvomorulin. We have proposed that these interactions are important in the assembly at sites of cell-cell contact of the membrane-cytoskeleton, which in turn initiates the development of the nonrandom distribution of the Na,K-ATPase. To directly investigate the functional significance of these protein-protein interactions in the spatial organization of the Na,K-ATPase, we analyzed the distribution of the Na,K-ATPase in fibroblasts transfected with a cDNA encoding the epithelial CAM, uvomorulin. Our results showed that expression of uvomorulin is sufficient to induce a redistribution of Na,K-ATPase from an unrestricted distribution over the entire cell surface in nontransfected cells to a restricted distribution at sites of uvomorulin-mediated cell-cell contacts in the transfected cells; this distribution is similar to that in polarized epithelial cells. This restricted distribution of the Na,K-ATPase occurred in the absence of tight junctions, but coincided with the reorganization of the membrane-cytoskeleton. These results support a model in which the epithelial CAM uvomorulin functions as an inducer of cell surface polarity of Na,K-ATPase through cytoplasmic linkage to the membrane-cytoskeleton.
Soc Gen Physiol Ser 1991
PMID:Role of the membrane-cytoskeleton in the spatial organization of the Na,K-ATPase in polarized epithelial cells. 165 95


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