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)

Anthopleurin-A (AP-A), a polypeptide with MW ca. 5500 (53 amino acids), isolated from the sea anemone, Anthopleura xanthogrammica (Brandt), elicited a potent positive inotropic effect but without an accompanying chronotropic effect on the isolated cardiac muscles of rat, rabbit, guinea pig and cat. Similarly in dogs and cats in situ, i.p. injections of AP-A increased the contractile force without effect on heart rate or blood pressure. The cardiotonic potency for AP-A was equivalent to that of isoproterenol but much greater than that for ouabain or glucagon on the isolated cardiac muscle. AP-A increased the contractile force (cardiac output) and decreased atrial pressure in dog heart during pentobarbital-induced failure. This inotropic effect was not inhibited by propranolol pretreatment. The Ca++ requirement to restore the contractile force was less in AP-A-treated than in ouabain or isoproterenol-treated tissues. After AP-A treatment, the cardiac contractility was more resistant to hypoxia and to low or high temperature stress than ouabain-treated or control preparations. AP-A at 5 10(-9) M increased the duration of the action potential, its mean rate of rise and conduction in the guinea-pig atria and ventricles. At the maximum effective concentration, AP-A did not inhibit Na+, K+-activated adenosine triphosphatase, phosphodiesterase (high Km and low Km) and cyclic 3',5'-adenosine monophosphate content of guinea-pig heart. AP-A (5 X 10(-8) to 5 X 10(-7) M) neither contracted nor relaxed the isolated vascular smooth muscle. The results suggest that AP-A may be useful in the clinical management of cardiac failure and as an experimental tool to study the pharmacology and physiology of cardiac muscle.
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PMID:A polypeptide (AP-A) from sea anemone (Anthopleura xanthogrammica) with potent positive inotropic action. 1 Apr 26

1. Guanylate cyclase of every fraction studied showed an absolute requirement for Mn2+ ions for optimal activity; with Mg2+ or Ca2+ reaction was barely detectable. Triton X-100 stimulated the particulate enzyme much more than the supernatant enzyme and solubilized the particulate-enzyme activity. 2. Substantial amounts of guanylate cyclase were recovered with the washed particulate fractions of cardiac muscle (63-98%), skeletal muscle (77-93%), cerebral cortex (62-88%) and liver (60-75%) of various species. The supernatants of these tissues contained 7-38% of total activities. In frog heart, the bulk of guanylate cyclase was present in the supernatant fluid. 3. Plasma-membrane fractions contained 26, 21, 22 and 40% respectively of the total homogenate guanylate cyclase activities present in skeletal muscle (rabbit), cardiac muscle (guinea pig), liver (rat) and cerebral cortex (rat). In each case, the specific activity of this enzyme in plasma membranes showed a five- to ten-fold enrichment when compared with homogenate specific activity. 4. These results suggest that guanylate cyclase, like adenylate cyclase, and ouabain-sensitive Na+ + K+-dependent ATPase (adenosine triphosphatase), is associated with the surface membranes of cardiac muscle, skeletal muscle, liver and cerebral cortex; however, considerable activities are also present in the supernatant fractions of these tissues which contain very little adenylate cyclase or ouabain-sensitive Na+ + K+-dependent ATPase activities.
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PMID:Guanylate cyclase. Subcellular distribution in cardiac muscle, skeletal muscle, cerebral cortex and liver. 1 Aug 90

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

Ca(++)-activated adenosine triphosphatase (Ca(++)-ATPase) was investigated in the rat cardiac muscle at neutral pH using tricine buffer. Reaction products indicating Ca(++)-ATPase activity were localized on the myocardial sarcolemma, sarcoplasmic reticulum, myofilaments, luminal and abluminal surfaces of capillary endothelium plasmatic membrane. The verification of the main enzymatic characteristics of Ca(++)-ATPase localization activity using this cytochemical procedure is under discussion.
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PMID:Ultracytochemical demonstration of Ca(++)-ATPase activity in the rat cardiac muscle. 138 15

The purpose of this study was to determine whether cardiac biochemical adaptations are induced by chronic exercise training (ET) of miniature swine. Female Yucatan miniature swine were trained on a treadmill or were cage confined (C) for 16-22 wk. After training, the ET pigs had increased exercise tolerance, lower heart rates during exercise at submaximal intensities, moderate cardiac hypertrophy, increased coronary blood flow capacity, and increased oxidative capacity of skeletal muscle. Myosin from both the C and ET hearts was 100% of the V3 isozyme, and there were no differences between the myosin adenosine triphosphatase (ATPase) or myofibrillar ATPase activities of C and ET hearts. Also, the sarcoplasmic reticulum Ca(2+)-ATPase activity and Na(+)-Ca2+ exchange activity of sarcolemmal vesicles were the same in cardiac muscle of C and ET hearts. Finally, the glycolytic and oxidative capacity of ET cardiac muscle was not different from control, since phosphofructokinase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase activities were the same in cardiac tissue from ET and C pigs. We conclude that endurance exercise training does not provide sufficient stress on the heart of a large mammal to induce changes in any of the three major cardiac biochemical systems of the porcine myocardium: the contractile system, the Ca2+ regulatory systems, or the metabolic system.
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PMID:Biochemical characterization of exercise-trained porcine myocardium. 183 67

As a series of studies on postmortem changes in the fine structure of porcine muscle, activity of two mitochondrial marker enzymes, succinate dehydrogenase (SDH) and magnesium dependent adenosine triphosphatase (Mg-ATPase), was measured and localized in cardiac, red and white muscles stored at 4 degrees C, -18 degrees C or -80 degrees C. The postmortem loss of SDH activity was most remarkable in cardiac muscle. The variation of SDH activity was proportional to the amount of absolute activity. The postmortem change of Mg-ATPase was more variable than SFH, though the activity was well preserved up to 15 weeks in all three types of porcine muscle stored at -80 degrees C. The loss of Mg-ATPase was most remarkable in red muscle stored at -18 degrees C or -80 degrees C. Cytochemical localization of SDH was between the outer and the inner mitochondrial membranes while that of Mg-ATPase was on the inner surface or matrix side of the inner membrane. Those localization was not altered by the difference in temperature and the duration of storage.
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PMID:Post-mortem changes in cytochemical localization and enzymological measurement of marker enzymes of the mitochondria, SDH and Mg-ATPase, of porcine muscle stored at 4 degrees C, -18 degrees C, or -80 degrees C. 213 22

There is evidence to suggest that increased nonenzymatic glycosylation (NEG) occurs in hyperglycemic states such as seen in diabetes mellitus. In order to examine the hypothesis that the development of cardiomyopathy in diabetes results from an increased nonenzymatic glycosylation of cardiac sarcolemmal proteins, rats were made diabetic by an intravenous (IV) injection of streptozotocin (65 mg/kg). Twelve weeks after the induction of diabetes, animal showed significantly lower heart rate, left ventricular systolic pressure, rate of contraction (+dp/dt), and rate of relaxation (-dp/dt), whereas left ventricular diastolic pressure was markedly increased. Furthermore, cardiac sarcolemmal Na+, K+ adenosine triphosphatase (ATPase) activity was significantly decreased in diabetic rats. When examined in cardiac crude membranes, as well as in purified sarcolemmal membranes prepared by two different procedures, the levels of NEG did not differ between control and diabetic animals; however, NEG levels were increased in kidney and skeletal muscle. These results indicate that chronic diabetes is associated with functional and biochemical alterations in cardiac muscle and suggest that NEG of cardiac sarcolemma may not play any role in the development of diabetic cardiomyopathy.
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PMID:Evidence against the involvement of nonenzymatic glycosylation in diabetic cardiomyopathy. 216 31

In response to increasing demand, the cardiac muscle has developed several adaptational mechanisms. Gene expression is modified in a quantitative and a qualitative way since the heart hypertrophies and since its structure changes to improve the efficiency of the contraction. The sarcomere modifications are both species- and tissue-specific. An isoenzymic shift of myosin from high adenosine triphosphatase (ATPase) activity form V-1 to low activity form V-3 occurs in all conditions in which V-1 is initially predominant, i.e., in rat (and also rabbit) ventricles and the atria of other species, including humans. It was not observed in conditions in which V-3 was predominant, as in human ventricles (and also in those of cats and pigs). Another shift from creatine kinase (CK) monomer M to CK B, the form that predominates in the fetal heart, is also observed. The sarcolemma is also modified, at least in rats. The digitalis receptor was characterized by studying the inotropic effect of the drug on an isolated heart preparation and on a purified preparation of sarcolemma with a high Na+,K(+)-ATPase activity by binding [3H]ouabain and ouabain-induced inhibition of the enzymatic activity. In hypertrophied heart, both the recovery of normal contractility after ouabain infusion and the release of previously bound ouabain infusion and the release of previously bound ouabain were slowed, as for fetal hearts. Changes in other inotropic receptors have also been reported. From a practical point of view, this means that screening of new inotropic agents has to be done on hypertrophied hearts and not, as usual, on normal tissue.
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PMID:Adaptational changes of sarcomere and sarcolemma during chronic cardiac overloading in rats and in humans. 248 18

Although insulin is known to elicit a positive inotropic effect in cardiac muscle preparations, very little is known concerning the mechanism of this action. In view of the crucial role played by the sarcoplasmic reticular (SR) calcium transport in cardiac contractile events, the effects of insulin on the pig heart SR were investigated. Insulin activated the SR Ca++-stimulated adenosine triphosphatase (ATPase) in a concentration-dependent manner (0.1 mU to 1 U/ml); maximal activation (125%) was seen at 0.1 to 1 U/ml of insulin. Kinetic studies revealed that the insulin-induced activation was due to an increase in the apparent Vmax of Ca++-stimulated ATPase without any alteration in the Km. Insulin was found to bind with SR membranes in a specific manner and this binding was rapid, saturable and displacable. The dose-related increase in the activation of Ca++-stimulated ATPase was related linearly (r = 0.98) to binding of insulin with SR membranes; 50% activation of Ca++-stimulated ATPase was found to occur at 13.5 fmol of insulin binding per mg of SR protein. When insulin was allowed to dissociate by a 100-fold dilution of the insulin-receptor complex, the activity of SR Ca++-stimulated ATPase also declined gradually. Furthermore, proteolytic digestion on the membrane with trypsin (3 micrograms/mg of protein) decreased both insulin binding as well as the increase in Ca++-stimulated ATPase activity by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of heart sarcoplasmic reticulum Ca++-stimulated adenosine triphosphatase by insulin. 252 88

This study examined effects of extracellular magnesium (Mg++0) on the positive inotropic and toxic actions of cardiotonic steroids in cardiac muscle isolated from guinea pig heart. Increasing concentrations of Mg++0 produced a negative inotropic effect in electrically paced, left atrial muscle and decreased the sensitivity to arrhythmogenic actions of digoxin without affecting the maximum developed tension observed before dysrhythmic activity. Other signs of toxicity such as contracture were less sensitive to the antagonistic effects of Mg++0. Estimates of fractional occupancy suggested that the increased tolerance to digoxin-induced arrhythmias was mediated by an altered responsiveness to given levels of receptor binding. Experiments in partially purified membrane preparations demonstrated that elevations in Mg++ increased affinity for [3H]ouabain without affecting binding site density. Na+,K+-adenosine triphosphatase activity in these membrane preparations was also enhanced by Mg++; however, increases in buffer Mg++ concentration had no effect on the Na+-pump in intact tissue. In summary, these results indicate that elevations in Mg++0 act directly on myocardium to diminish the sensitivity to cardiotonic steroid-induced arrhythmias. Furthermore, data suggest that this antagonistic action of Mg++0 is not mediated by alterations in receptor binding or Na+-pump reserve capacity.
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PMID:Extracellular magnesium and cardiotonic steroid toxicity in isolated myocardial preparations. 253 49


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