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)

Several data suggest that in species such as humans, dogs or guinea pigs, sarcomere protein changes do not explain the physiologic modifications that occur in the heart in response to chronic overload. In the guinea pig, e.g., the shortening velocity of an intact papillary muscle negatively correlates with the degree of hypertrophy while the shortening velocity of a skinned hypertrophied fiber does not correlate with heart weight. This review is an attempt to summarize quantitatively data concerning membrane proteins in chronic experimental cardiac overload. With that respect, 2 groups of proteins can be distinguished: (1) the group formed by the calcium-activated adenosine triphosphatase (Ca2(+)-ATPase) of the sarcoplasmic reticulum, the beta 1-adrenergic and muscarinic receptors and the low affinity isoform of the Na+K(+)-ATPase. The synthesis of these proteins is not activated by the process of hypertrophy and consequently their density diminished and their total number per myocyte or per ventricle is unchanged. (2) The second group is formed by the calcium channels and the high affinity isoform of the Na+K(+)-ATPase whose density, in contrast, is unchanged or even increases. Their synthesis is therefore stimulated commensurately with the degree of overload and their total number per myocyte is enhanced. These data suggest that search in the field of inotropes must take into account the fact that the keys that these drugs represent must be modeled as a function of the lock they have to fit into.
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PMID:Changes in membrane proteins in chronic mechanical overload of the heart. 213 54

Epinephrine was infused intravenously in 9 normal volunteers to plasma concentrations similar to those found after acute myocardial infarction. This study was undertaken on 3 occasions after 5 days of treatment with placebo or the beta-adrenoceptor antagonist, atenolol, which is relatively beta 1 selective, or timolol, which blocks both beta 1 and beta 2 receptors. Epinephrine increased the systolic blood pressure (BP), decreased the diastolic BP and increased the heart rate modestly. These changes were prevented by atenolol. However, after timolol the diastolic BP rose by +19 mm Hg and heart rate fell by -8 beats/min. Epinephrine caused the corrected QT interval to lengthen (0.36 +/- 0.02 to 0.41 +/- 0.06 second). No significant changes were found in the corrected QT interval when subjects were pretreated with atenolol or timolol. The serum potassium decreased from 4.06 to 3.22 mmol/liter after epinephrine. Serum potassium decreased to a lesser extent to 3.67 mmol/liter after atenolol and actually increased to 4.25 mmol/liter after timolol. In a further study with a similar design another nonselective beta blocker propranolol also increased potassium after epinephrine. While atenolol also prevented hypokalemia in this study, it did not block the beta 2-receptor mediated decrease in diastolic BP. Epinephrine-induced hypokalemia results from stimulation of a beta-adrenoceptor linked to membrane sodium/potassium adenosine triphosphatase causing potassium influx. This appears to be predominantly mediated by beta 2 receptors although beta 1 receptors may also play a part.
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PMID:Epinephrine-induced hypokalemia: the role of beta adrenoceptors. 301 Jun 93

High-affinity ouabain binding to Na+/K(+)-ATPase (sodium- and potassium-transport adenosine triphosphatase (EC 3.6.1.37)) requires phosphorylation of the alpha subunit of the enzyme either by ATP or by inorganic phosphate. For the native enzyme (alpha/beta 1), the ATP-dependent reaction proceeds about 4-fold more slowly in the absence of Na+ than when saturating concentrations of Na+ are present. Hybrid pumps were formed from either the alpha 1 or the alpha 3 subunit isoforms of Na+/K(+)-ATPase and a chimeric beta subunit containing the transmembrane segment of the Na+/K(+)-ATPase beta 1 isoform and the external domain of the gastric H+/K(+)-ATPase beta subunit (alpha/NH beta 1 complexes). In the absence of Na+, these complexes show a rate of ATP-dependent ouabain binding from approximately 75-100% of the rate seen in the presence of Na+ depending on buffer conditions. Nonhydrolyzable nucleotides or treatment of ATP with apyrase abolishes ouabain binding, demonstrating that ouabain binding to alpha/NH beta 1 complexes requires phosphorylation of the protein. Buffer ions inhibit ouabain binding by alpha/NH beta 1 in the absence of Na+ rather than promote ouabain binding, indicating that they are not substituting for sodium ions in the phosphorylation reaction. The pH dependence of ATP-dependent ouabain binding in the presence or absence of Na+ is similar, suggesting that protons are probably not substituting for Na+. Hybrid alpha/NH beta 1 pumps also show slightly higher apparent affinities (2-3-fold) for ATP, Na+, and ouabain; however, these are not sufficient to account for the increase in ouabain binding in the absence of Na+. In contrast to phosphoenzyme formation and ouabain binding by alpha/NH beta 1 complexes in the absence of Na+, ATPase activity, measured as release of phosphate from ATP, requires Na+. These data suggest that the transition from E1P to E2P during the catalytic cycle does not occur when the sodium binding sites are not occupied. Thus, the chimeric beta subunit reduces or eliminates the role of Na+ in phosphoenzyme formation from ATP, but Na+ binding or release by the enzyme is still required for ATP hydrolysis and release of phosphate.
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PMID:The influence of beta subunit structure on the interaction of Na+/K(+)-ATPase complexes with Na+. A chimeric beta subunit reduces the Na+ dependence of phosphoenzyme formation from ATP. 777 54

The activity of the Na+/H+ exchanger was studied by measuring the effects of intracellular pH (pHi) and extracellular Na+ [(Na+)o] on pHi recovery and 22Na uptake in rat adipocytes. The resting pHi was acidified from 7.30 +/- 0.02 to 6.99 +/- 0.01 with nigericin in the absence of (Na+)o. pHi recovery induced by 30 mM NaCl was blocked by 100 microM amiloride. The reversibility of the exchanger was studied by Na+ loading, which raised the pHi from 7.30 +/- 0.02 to 7.50 +/- 0.01, and by removing (Na+)o, which decreased pHi to 6.97 +/- 0.01. Both functions of the exchanger, forward and backward, were inhibited by amiloride. The Na+/H+ exchanger was inactive at pHi higher than 7.1 and became increasingly active as pHi decreased to 6.2 (22Na+ uptake, 0.029 +/- 0.003 vs. 0.155 +/- 0.009 nmol/10(5) cells.2.5 min; P < 0.001); this 5-fold stimulation was largely abolished by amiloride (0.025 +/- 0.002; P < 0.001). Na+ influx was also increased as a function of (Na+)o, with an apparent Km of 35 mM. Respective 5- and 44-fold stimulations at 5 mM (0.135 +/- 0.007) and 140 mM (Na+)o (1.228 +/- 0.046 nmol/10(5) cells.2.5 min; P < 0.001) were inhibited by ethylisopropylamiloride. Isoproterenol (Iso; 100 nM) and agents that stimulate cAMP production, such as forskolin (10 microM) and theophyline (1 mM), inhibited the activity of amiloride-sensitive 22Na+ uptake by 85%. Iso inhibited the Na+/H+ exchanger, without affecting the Na+/K(+)-adenosine triphosphatase-dependent and the Na+/K+/Cl- cotransport mechanisms. (Bu)2cAMP (1 mM), a membrane-permeant cAMP analog, mimicked the effects of Iso on the exchanger. The inhibitory effect of Iso was blocked by propranolol, but not by metoprolol, a beta 1-antagonist. In addition, the alpha-adrenergic agonists, phenylephrine (alpha 1) and clonidine (alpha 2), and the alpha-antagonists, prazocin (alpha 1) and yohimbine (alpha 2), did not prevent Iso-induced inhibition of the exchanger. In conclusion, rat adipocytes possess a reversible Na+/H+ exchange mechanism, which is activated by low pHi and normal (Na+)o and is inhibited by Iso via a beta 2-adrenergic receptor stimulation and a cAMP-dependent mechanism.
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PMID:Activation of the Na+/H+ exchanger by cellular pH and extracellular Na+ in rat adipocytes; inhibition by isoproterenol. 778 40

The effects of thyroid hormone (T3) treatment on liver Na,K-adenosine triphosphatase (Na,K-ATPase) at the levels of subunit messenger RNA (mRNA), enzymatic activity, and enzyme content were studied in euthyroid rats injected for 5 consecutive days with T3. Northern and slot blot analyses of polyadenylated mRNA revealed that T3 treatment coordinately increases the level of mRNA encoding the alpha 1- and beta 1-subunits, approximately 4- and 3-fold, respectively, above basal levels. To determine whether this increase in the subunit mRNA consequently results in an increase in the synthesis of the enzyme, a modified liver cell fractionation procedure was developed, and the subcellular fractions from control and T3-treated livers were examined biochemically. Western blot analysis and Na,K-ATPase assay demonstrated that T3 treatment resulted in a 2-fold increase in both the amount and activity of the enzyme. Furthermore, the Western blot analysis of endoglycosidase-H-treated membrane fractions revealed an increase in the amount of the precursor beta-subunit in the T3-treated liver rough microsomal fraction, suggesting that an increase in subunit synthesis contributes at least partially to the increase in the rat liver Na,K-ATPase by T3 treatment.
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PMID:The effect of thyroid hormone treatment on the gene expression and enzyme activity of rat liver sodium-potassium dependent adenosine triphosphatase. 783 97

Thyroid hormone (T3) increases the transcription of the sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) gene (SERCA 2) through three thyroid hormone response elements. The existence of repetitive cis elements with different configurations is likely to serve specific functions such as interactions with nuclear transcription factors. In addition, the presence of different T3 receptor isoforms (T3Rs) may contribute to another level of complexity in providing specificity for T3 action. In this study, we investigated T3R alpha 1-vs. T3R beta 1-specific interactions with the myocyte enhancer-specific factor-2 (MEF-2) on the expression of the SERCA 2 gene in transient transfection assays in embryonal heart-derived H9c2 cells. MEF-2a in combination with either T3R alpha 1 or T3R beta 1 isoforms resulted in a 2.5-fold increase in SERCA 2 transgene expression in the absence of T3. Addition of T3 did not induce any further increase in SERCA 2 expression when T3R alpha 1 and MEF-2a expression vectors were cotransfected. In contrast, in the presence of T3R beta 1 and MEF-2, the addition of T3 increased chlorampenicol acetyltransferase activity by an additional 2.2-fold to a total 5.5-fold increase. The interaction between MEF-2a and T3R is transcription factor specific because another factor that binds to MEF-2 consensus sites (heart factor 1b) was not able to interact with T3R. In addition, MEF-2a failed to interact with other nuclear factors (cAMP response element-binding protein and Egr-1) that stimulate SERCA 2 gene transcription. In addition, we found that a single homologous thyroid hormone response element is not able to mediate the interactions between MEF-2a and T3Rs to increase SERCA 2 gene transcription. Our findings point to T3R isoform-specific interactions with a cell type-specific transcription factor (MEF-2) in the regulation of SERCA 2 gene expression.
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PMID:Transcription of the rat sarcoplasmic reticulum Ca2+ adenosine triphosphatase gene is increased by 3,5,3'-triiodothyronine receptor isoform-specific interactions with the myocyte-specific enhancer factor-2a. 897 81

Multiple cyst formation with fluid retention is a characteristic structural abnormality in polycystic kidney disease (PKD). Na/K adenosine triphosphatase (ATPase) is a major transporting membrane protein that is ubiquitous in the epithelial cell, which has been thought to be involved in cystogenesis. We have investigated the molecular and histologic basis of Na/K ATPase activity in experimental PKD in vivo. Rats were treated with diphenylthiazole (100 mg/100 gm body weight), and cyst formation was examined histologically. Na/K ATPase activity was measured enzymatically by using a fluorometric method, and reverse transcription-competitive polymerase chain reaction (RT-PCR) analysis was used to quantitate mRNA levels in the isolated single nephron segment. Kidneys were immunostained with subunit-specific antibodies to determine the localization of Na/K ATPase in the epithelial cell. The enzyme activity increased in the cortical collecting duct from 25.9 +/- 3.5 mmol/Lpmol/mm/min to 72.9 +/- 6.8 pmol/mm/min and in the outer medullary collecting duct from 13.0 +/- 3.9 mmol/Lpmol/mm/min to 58.5 +/- 9.8 pmol/mm/min (n = 6, p < 0.01); however, all other segments showed no significant changes. No significant alternation in alpha 1- and beta 1-subunits of Na/K ATPase mRNA levels was observed by competitive PCR assay in either segment. The enzyme was stained at the basolateral membrane even in the cystic tubules. Na/K ATPase activity was up-regulated in the cyst-formed kidney, but this was not accompanied with transcriptional up-regulation. Increased Na/K ATPase activity at normal locations may play a role in abnormal net fluid transport in the development and progression of experimental PKD.
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PMID:A role for Na/K adenosine triphosphatase in the pathogenesis of cyst formation in experimental polycystic kidney disease. 914 48