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 rats were given potassium bichromate (K2Cr2O7) in dose of 2 and 5 mg/kg of body weight and magnesium chloride (MgCl2) in dose of 500 mg/kg for a period of 30 days. The two compounds were also given conjointly (K2Cr2O7-5 mg+MgCl2-500 mg). There were carried out histopathological as well as histochemical examinations of acid phosphatase activity, alkaline phosphatase activity and adenosine triphosphatase activity in the liver. With small doses (2 mg) of potassium bichromate no changes have been stated. With larger doses (5 mg) of potassium bichromate an increase of histochemical reaction to acid phosphatase as well as forming of histopathological changes such as parenchymatous degeneration, steatosis of hepatocytes and their necrobiosis have been observed. There has not been found any protective action of magnesium chloride on the cytotoxic activity of potassium bichromate on the liver cell.
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PMID:[Histopathologic and histochemical examination of rat liver after prolonged experimental application of potassium bichromate]. 136 4

Bepridil is an antianginal agent with multiple therapeutic actions. It decreases calcium influx through potential-dependent and receptor-operated sarcolemmic calcium channels and acts intracellularly as a calmodulin antagonist and calcium sensitizer. Thus, in cardiac muscle it enhances the sensitivity of troponin C to calcium, stimulates myofibrillar adenosine triphosphatase activity, removes calmodulin's inhibitory effect on sarcoplasmic reticulum calcium release, and inhibits sodium-calcium exchange--actions that tend to offset the effects of calcium influx blockade on cardiac contractile force. However, in vascular smooth muscle where the calcium-calmodulin complex promotes muscle contraction by activating myosin light-chain kinase phosphorylation of contractile proteins, calmodulin antagonism, coupled with bepridil's blockade of calcium influx, leads to vasorelaxation. In animal models of ischemia, bepridil and other calmodulin inhibitors show antiarrhythmic efficacy following reperfusion. Additionally, interfering with calmodulin's role in sympathetic nerve terminal function may help to limit the ischemia-induced catecholamine release that contributes to arrhythmogenesis. Bepridil shows a lidocaine-like fast kinetic block of inward sodium current (as distinct from the slow or intermediate kinetic inhibition expressed by encainide or quinidine, respectively). This inhibition is pH-dependent; activity is expressed to a greater degree at lower pH levels. This, this potentially antiarrhythmic mechanism is activated by conditions of ischemia. Bepridil's blockade of outward potassium currents and its inhibition of sodium-calcium exchange increase action potential duration and ventricular refractoriness, prolong the QT interval, and form the basis for a class III antiarrhythmic mechanism. Because hypokalemia also prolongs the QT interval, the addition of bepridil in the presence of hypokalemia can lead to excessive prolongation. Bepridil both increases myocardial oxygen supply through coronary vasodilation and decreases myocardial oxygen demand through mild heart rate and afterload reduction, and shows potential antiarrhythmic activity through class IB, III, and IV mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacology of bepridil. 137 85

Acquired resistance to cisplatin (cis-diamminedichloroplatinum (II)) has been generated in vitro in the 41M human ovarian carcinoma cell line, established from a previously untreated patient. Three cisplatin-resistant variants were selected at approximately 2, 4 and 6-fold resistance (in terms of 50% inhibitory concentrations), in order to study the underlying mechanisms of acquired cisplatin resistance. Compared to the parent line, platinum accumulation following exposure to equimolar concentrations of cisplatin was on average (across the entire concentration range) 2.9, 3.6 and 4.8-fold lower in the 41McisR2, 41McisR4 and 41McisR6 cell lines, respectively. Thus the difference in uptake corresponded closely with their resistance factor in the three resistant variants. Moreover, a significant reduction in platinum accumulation was observed as early as 5 min after exposure to cisplatin in the 41M vs 41McisR6 cell lines. Platinum accumulation was similar in all cell lines following exposure to equitoxic concentrations (2 h IC50) of cisplatin. Enhanced efflux of drug was not observed between the 41M and 41McisR6 cells. In addition, there was no difference in intracellular glutathione (GSH) levels. Our previous studies have shown no indication of metallothionein involvement and the decrease in cisplatin uptake in the 41McisR6 cells was reflected by a similar reduction in DNA interstrand cross-links (ISC) formation. These results suggest that the mechanism of acquired resistance to cisplatin in the 41McisR6 cell line may be predominantly due to reduced drug uptake. The 41McisR6 cells were not found to be cross-resistant to ouabain, a postulated specific inhibitor of sodium-potassium adenosine triphosphatase (Na+, K(+)-ATPase), suggesting that decreased cisplatin accumulation in these cells is probably not regulated by alterations in their Na+, K(+)-ATPase levels, and Na+ potential across the plasma membrane. Cellular accumulation of a novel class of platinum (IV) ammine/cyclohexylamine dicarboxylates, which exhibit enhanced cytotoxicity over cisplatin and completely circumvent resistance to cisplatin in the 41McisR line, was also examined. The data suggests that increased accumulation of these compounds, as a result of their enhanced lipophilicity, could account for the dramatic increase in their potency over cisplatin.
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PMID:Reduced drug accumulation as a major mechanism of acquired resistance to cisplatin in a human ovarian carcinoma cell line: circumvention studies using novel platinum (II) and (IV) ammine/amine complexes. 145 52

Rapid advances in the molecular genetics of Duchenne muscular dystrophy (DMD) and the discovery and localization of the gene product dystrophin has brought new hope that successful treatment for this disease may not be too far away. Dystrophin has been postulated to have a mechanical function, helping to resist stress associated with muscle contraction. The presence of dystrophin in low concentrations in muscle cells, its expression in nervous tissue and the observation that hypercontraction of the sarcomeres precedes membrane rupture make the hypothesis unlikely. On the basis of an analogy with a cytoskeletal protein ankyrin, which is associated with the sodium/potassium adenosine triphosphatase (ATPase) in the kidney, it is possible that dystrophin deficiency leads initially to an increased but inefficient calcium-ATPase activity, which pumps calcium out of the cell. Partial failure of the pump would result in intracellular accumulation of calcium, hypercontractions of the sarcomeres, rupture of the cell membrane, massive influx of calcium and cell necrosis.
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PMID:Pathogenesis of Duchenne muscular dystrophy: the calcium hypothesis revisited. 149 54

Methyl isocyanate (MIC) interaction with the rabbit erythrocyte membrane increased the fluidity of the membrane and decreased the osmotic fragility of erythrocytes both in vitro and in vivo in rabbits intoxicated with MIC subcutaneously. MIC inhibited both acetylcholinesterase (AChE) and adenosine triphosphatase (ATPase) activities of erythrocytes dose-dependently in vitro, while in vivo a decreased trend in ATPase activity with unaltered AChE activity was observed. MIC also caused significant decrease in plasma sodium level with corresponding increase in potassium level in rabbits. The observed effects are due to MIC, per se, as the hydrolysis products of MIC, methylamine and N,N'-dimethylurea did not affect the erythrocyte fluidity and enzymes activities both in vitro and in vivo while they increased the osmotic fragility of erythrocytes in vivo in rabbits administered subcutaneously in equimolar concentration to MIC dosage. Inhibition of Na(+)-K(+)-dependent ATPase with altered permeability to cations and also probably water transport of plasma membrane due to MIC interaction are envisaged.
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PMID:Acute toxicity of methyl isocyanate in rabbit: in vitro and in vivo effects on rabbit erythrocyte membrane. 153 91

Omeprazole is a new hydrogen-potassium adenosine triphosphatase antagonist with indications for severe reflux esophagitis and Zollinger-Ellison syndrome. Side effects involving the liver have consisted of minimal elevations of hepatocellular enzymes with higher dosages. We present what we believe is the first reported case of fulminant hepatic failure related to omeprazole.
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PMID:Fulminant hepatic failure related to omeprazole. 155 42

Basolateral membranes from rabbit proximal colon were prepared from isolated colonocytes throughout postnatal maturation, using a modification of published techniques. In suckling (14-20 day) and post-weaning/mature (35-49 day) animals, membranes were purified approx. 10-fold, based upon the enrichment of ouabain-sensitive, sodium-potassium dependent adenosine triphosphatase activity. Membrane lipid analyses demonstrated age-dependent increases in total cholesterol and the cholesterol/phospholipid molar ratio, as well as decreases in phosphatidylethanolamine content and the fatty acid unsaturation index. Fluidity of basolateral membranes and membrane liposomes, determined from fluorescence anisotropy measurements using the lipid probes 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, demonstrated significant, ontogenic decreases in fluidity; and, additional studies showed that fluidity changes occurred early in the weaning period (by day 24 postnatally). Arrhenius plots of liposome anisotropies suggested a bilayer lipid thermotropic transition temperature of 22 degrees C in sucklings 26 degrees C in mature rabbits. These findings demonstrate that ontogeny of colonic basolateral membranes is associated with significant modulations in lipid composition and fluidity.
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PMID:Ontogeny of proximal colon basolateral membrane lipid composition and fluidity in the rabbit. 161 27

The role of the mammalian mesonephric kidney is not completely understood. It has been established that outpouchings of the mesonephric excretory ducts give origin to parts of the urogenital system of the adult. It is also known that mammalian mesonephric urine is formed as an ultrafiltrate. The mesonephric renal tubules have Na+/K+ adenosine triphosphatase (Na+/K+ pump), secrete phenol red, and reabsorb protein. Prior to this work, the possibility of epithelial transport of ions and metabolic substrates across mammalian mesonephric tubules had not been directly evaluated. Proximal mesonephric tubules obtained from 17 to 18-days-old rabbit embryos were isolated and perfused in vitro. Continuous intracellular electrical recordings were obtained with Ling-Gerard-type microelectrodes and a high input impedance electrometer. In tubules perfused and bathed in standard mammalian Ringer's solutions, the average transmembrane electrical cell potential difference (PD) was -43 +/- 0.5 mV (76 cells). The cellular PD decreased by 30 percent when the temperature of the bath was cooled from 37 degrees C to 30 degrees C. The cells also depolarized by 25 percent in the first five minutes of exposure to 0.1 mM ouabain. In addition, the cell PD decreased by 40 and 60 percent when the extracellular potassium concentration was raised from five to 25 and 50 mM, respectively. The uptake of glucose and alanine was similarly electrogenic (delta:1 mV/mM). The cell PD, the K+ conductance, and the electrogenicity induced by luminal exposure to 5 mM glucose or alanine are significantly lower in the mesonephric as compared to the metanephric proximal tubules of the rabbit. These observations suggest that sodium-coupled transepithelial transport mechanisms, driven by the Na+/K+ pump, are already present in the mammalian mesonephric proximal tubule. Increases in the number of Na+/K+ pumps, conductive K+ channels, and sodium-substrate cotransporters seem to be at the core of proximal tubular ontogeny.
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PMID:Renal ontogeny: epithelial transport in the mammalian mesonephric proximal tubule. 164 30

Murine autoimmune gastritis, induced by neonatal thymectomy, bears a striking similarity in pathology to the human autoimmune disease, pernicious anemia. Autoantibodies to parietal cells are found in both murine and human diseases. Monoclonal immunoglobulin G autoantibodies, obtained from neonatally thymectomized mice, have previously been shown to recognize two groups of gastric parietal cell antigens. In the present study, it is shown that two of these monoclonal autoantibodies, designated 1H9 and 2B6, are directed against the alpha subunit and beta subunit, respectively, of the gastric hydrogen-potassium-stimulated adenosine triphosphatase (H+,K(+)-ATPase; proton pump). Monoclonal antibody 1H9 showed reactivity by immunoblotting with a 95-kilodalton component of dog gastric tubulovesicular membranes and with a fusion protein containing the hydrophilic domain of the alpha subunit of the H+,K(+)-ATPase. Monoclonal antibody 2B6 reacted by immunoblotting with the 60-90-kilodalton glycoprotein (beta subunit) of the tomato lectin-purified dog H+,K(+)-ATPase and with the 60-90-kilodalton autoantigen purified with human parietal cell autoantibodies. Monoclonal antibody 2B6 also reacted with the deglycosylated 35-kilodalton core protein of the tomato lectin-purified 60-90-kilodalton beta subunit and of the purified 60-90-kilodalton autoantigen. Parietal cell autoantibody-positive sera from 20 mice with experimentally induced gastritis showed reactivity predominantly with the alpha and/or beta subunit of the gastric H+,K(+)-ATPase. Therefore, it is concluded that the major molecules targeted by parietal cell autoantibodies from mice with neonatal thymectomy-induced murine autoimmune gastritis and from humans with pernicious anemia are identical.
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PMID:The parietal cell autoantigens recognized in neonatal thymectomy-induced murine gastritis are the alpha and beta subunits of the gastric proton pump [corrected]. 164 25

Ciliary epithelium was isolated from the rabbit eye and used as a source of plasma membrane material for sodium, potassium-adenosine triphosphatase (Na,K-ATPase) measurements. In the presence of 12(R)-hydroxyeicosatetraenoic acid [12(R)HETE], Na,K-ATPase (ouabain-sensitive ATPase) activity was reduced from 22.5 to 16.3 microM phosphate released/mg protein/hr. Ouabain-insensitive ATPase activity was not altered by 12(R)HETE. No changes in ciliary epithelium ATPase activity were observed in the presence of 12(S)HETE. In parallel studies with conscious rabbits, 12(R)HETE applied topically to the eye was found to lower intraocular pressure (IOP). It is possible that the IOP-lowering effect of 12(R)HETE may be, in part, associated with its ability to suppress the Na,K-ATPase activity of the ciliary epithelium.
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PMID:The influence of 12(R)-hydroxyeicosatetraenoic acid on ciliary epithelial sodium, potassium-adenosine triphosphatase activity and intraocular pressure in the rabbit. 165 Dec 97


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