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)

We investigated the "receptor-effector-coupling" in the beta-adrenoceptor- and the Na+, K(+)-ATPase-mediated systems in nonfailing hearts and terminally failing human myocardium from patients with cardiomyopathy. The density of beta-adrenoceptors in the failing human myocardium was significantly (p less than 0.01) lower as compared with nonfailing hearts, whereas the receptor density and affinity measured by [3H]ouabain binding (cardiac glycoside receptor) was not different in either group. The maximal inotropic response to isoprenaline was significantly reduced in papillary muscle strips from failing human hearts (2.1 +/- 0.5 mN) as compared with control hearts (8.0 +/- 1.0 mN; p less than 0.05). Ouabain remained effective in both groups (6.8 +/- 1.0 vs. 5.5 +/- 0.6 mN; NS). The positive inotropic response due to extracellular Ca2+ elevation (1.8-15 mM) was studied for comparison. Maximal Ca2+ effects were reduced by 30% in failing human myocardium (7.2 +/- 0.5 mN vs. 5.1 +/- 0.8 mN, p less than 0.05). Ouabain had effectiveness (95%) similar to that of Ca2+ in nonfailing and failing human cardiac muscle. It is concluded that treatment with cardiac glycosides may still be effective in end-stage heart failure with "downregulated" beta-adrenoceptors, as judged from these in vitro studies.
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PMID:Effectiveness of cardiac glycosides in human myocardium with and without "downregulated" beta-adrenoceptors. 169 27

The inotropic actions of various drugs known to increase force of contraction in isolated mammalian cardiac muscle were investigated in electrically driven (1 Hz) guinea-pig left atria under both normal [K+]o (4.7 mM) and high [K+]o (22 mM). Under normal [K+]o a concentration-dependent increase in force of contraction could be confirmed with the beta-adrenoceptor agonist, isoprenaline, the cyclase activator, forskolin, the inhibitors of the cyclic AMP-phosphodiesterase (PDE), amrinone, IBMX, and OPC 8212, the Na+ channel activators, DPI 201-106, SDZ 210-921, veratridine, and ATX II, the Na(+)-ionophore monensin, the inhibitor of Na+/K(+)-ATPase, ouabain, and the Ca2+ channel activators, Bay K 8644, CGP 28 H 392, and SDZ 202-791. Partial depolarization of the muscle preparations by increasing [K+]o in the organ bath to 22 mM completely abolished the positive inotropic action of the Na+ channel-activating drugs. In contrast, the effects of the other compounds were still present, although changes in the maximal force development were observed. The efficacy of the PDE inhibitors amrinone and IBMX were slightly increased; the maximal effects of isoprenaline, monensin, forskolin, and OPC 8212 were unchanged; the effect of ouabain decreased to about half maximal values; while the efficacy of the Ca2+ channel activators were either unchanged (CGP 28 392) or decreased (Bay K 8644 and SDZ 202-791). The results suggest that inactivation of cardiac fast Na+ channels by partially depolarizing isolated, electrically driven atria is a suitable model to distinguish between cardiotonic agents acting through activation of Na+ channels and those with other mechanisms of action.
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PMID:Identification of cardiotonic sodium channel activators by potassium depolarization in isolated guinea-pig atria. 170 Feb 27

During normal relaxation in rabbit, guinea-pig, and rat ventricular muscle, the Na-Ca exchange system competes with the SR Ca pump, with the former being responsible for about 20-30% of the Ca removal from the cytoplasm. Ca extrusion via Na-Ca exchange is Em-sensitive, whereas Ca uptake by the SR is not. Neither the sarcolemmal Ca-ATPase pump nor mitochondrial Ca uptake appear to contribute significantly to the decline of [Ca]i during relaxation. Furthermore, the diastolic efflux of Ca from cardiac muscle cells appears to be primarily attributable to Na-Ca exchange and not the sarcolemmal Ca-ATPase pump. In rabbit ventricle Ca entry via Na-Ca exchange is favored thermodynamically during much of a normal twitch contraction and Ca extrusion occurs primarily between beats. In rat ventricle Ca efflux via Na-Ca exchange occurs during the contraction and net Ca influx may occur between beats. This fundamental difference in Ca fluxes during the cardiac cycle in rat versus rabbit ventricle may be a simple consequence of the shorter action potential duration and higher aNai in rat ventricle (due to the effects of Em and [Na] and [Ca] gradients on Na-Ca exchange).
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PMID:Species differences and the role of sodium-calcium exchange in cardiac muscle relaxation. 178 64

The sarcoplasmic reticulum (SR) ryanodine receptor was studied in SR vesicles isolated from the vastus intermedius skeletal muscle and cardiac muscle of malignant hyperthermia-susceptible (MHS) and normal pigs. MHS and normal heavy SR preparations isolated from the vastus intermedius muscle had similar yields, polyacrylamide gel electrophoretic patterns, Ca2(+)-ATPase activities, mitochondrial enzyme activities, calsequestrin contents, and maximal [3H]ryanodine-binding activities. However, while half-maximal calcium concentrations (Ca0.5) for stimulation of MHS and normal vastus intermedius SR [3H]ryanodine binding were not significantly different, the Ca0.5 for inhibition of [3H]ryanodine binding to MHS vastus intermedius SR (76 +/- 17 microM) was significantly greater than to normal SR (16 +/- 9 microM). MHS vastus intermedius SR also exhibited a significantly lower Kd value (62 +/- 15 nM) for [3H]ryanodine binding compared with normal SR (Kd = 284 +/- 102 nM). These values for MHS and normal vastus intermedius SR are similar to those reported using SR isolated from a muscle composed of predominantly fast-twitch fibers, indicating the similarity of the ryanodine receptor in fast- and slow-twitch skeletal muscles. In contrast, there were no differences in the properties of the ryanodine receptor of porcine cardiac SR isolated from MHS and normal pigs. We therefore conclude that there is a defect in the SR ryanodine receptor of both slow- and fast-twitch skeletal muscle fiber types but not in cardiac muscle of MHS individuals.
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PMID:Ryanodine receptor in different malignant hyperthermia-susceptible porcine muscles. 182 8

1. Female Wistar rats were randomly assigned to control (C) or exercising (T) groups and subsequently portioned into 1, 3, 5 and 10 day T and C groups. The T groups completed a progressive endurance running program. Biochemical indices of adaptation were measured in cardiac muscle and in plantaris and soleus muscles of C and T animals after their last exercise bout. 2. In cardiac muscle, myofibrillar ATPase activity was significantly elevated in the 3T (0.241 +/- 0.031) and 5T (0.242 +/- 0.013) groups (P less than or equal to 0.05) compared to their respective controls (3C = 0.187 +/- 0.015 and 5C = 0.190 +/- 0.007). 3. After 10 days of training cardiac myofibrillar ATPase activity was elevated by 17% but this was not significant (P greater than or equal to 0.05). 4. No changes in myofibrillar ATPase activity were seen in skeletal muscle (P greater than or equal to 0.05), however, hexokinase activity progressively increased and was significantly elevated in the 3T, 5T and 10T soleus and plantaris muscles of rats over controls (P less than or equal to 0.05). 5. Minimal nonsignificant changes were noted in the hexokinase activity of the hearts of all T groups (P greater than or equal to 0.05). 6. These results indicate that metabolic adaptation of the heart and skeletal muscles takes place after as little as three training sessions. 7. Although the adaptation of the skeletal muscles continually progresses, the adaptation of the heart appears to be transitory.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical adaptation of cardiac and skeletal muscle to physical activity. 182 40

Xestoquinone (XQN), a novel cardiotonic principle from the sea sponge Xestospongia sapra, enhanced Ca+(+)-induced tension development of chemically skinned fibers from guinea pig cardiac muscle, even at both free Ca++ concentrations as low as -log molar free Ca++ (pCa) 9 to 8. In skinned fibers from guinea pig skeletal muscle, XQN (10 microM) also increased developed tension with a similar Ca++ dependence to that for cardiac fibers. In contrast to the unique Ca+(+)-dependence of XQN effects, the reference drug sulmazole enhanced Ca+(+)-induced tension development of skinned cardiac fibers at pCa 6.6 but did not affect it at pCa 8. In natural actomyosin from canine cardiac muscle, as well as in that from rabbit skeletal muscle, XQN (1-30 microM) enhanced the rate and extent of superprecipitation. Moreover, XQN produced a concentration-dependent increase in the myofibrillar ATPase activity of canine cardiac muscle, even at very low free Ca++ concentrations below the normal threshold for ATPase activation (pCa 9-8). The natural actomyosin ATPase activity of chicken smooth muscle was not influenced by XQN (up to 30 microM). In cardiac myofibrils, no significant difference was observed between the bound 45Ca+(+)-pCa relationship curves in the presence and absence of XQN (10 microM). Furthermore, XQN (30 microM) did not cause or potentiate Ca+(+)-induced Ca++ release from cardiac sarcoplasmic reticulum vesicles. These observations suggest that XQN directly activates actomyosin ATPase activity of cardiac and skeletal myofibrils, thus producing an enhanced superprecipitation activity as well as an increase in skinned fiber contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Xestoquinone, a novel cardiotonic agent activates actomyosin ATPase to enhance contractility of skinned cardiac or skeletal muscle fibers. 182 30

The role of ATP-dependent calcium uptake into intracellular storage compartments is an essential feature of hormonally induced calcium signaling. Thapsigargin, a non-phorboid tumor promoter, increasingly is being used to manipulate calcium stores because it induces a hormone-like elevation of cytosolic calcium. It has been suggested that thapsigargin acts through inhibition of the endoplasmic reticulum calcium pump. We have directly tested the specificity of thapsigargin on all of the known intracellular-type calcium pumps (referred to as the sarcoplasmic or endoplasmic reticulum Ca-ATPase family (SERCA]. Full-length cDNA clones encoding SERCA1, SERCA2a, SERCA2b, and SERCA3 enzymes were expressed in COS cells, and both calcium uptake and calcium-dependent ATPase activity were assayed in microsomes isolated from them. Thapsigargin inhibited all of the SERCA isozymes with equal potency. Furthermore, similar doses of thapsigargin abolished the calcium uptake and ATPase activity of sarcoplasmic reticulum isolated from fast twitch and cardiac muscle but had no influence on either the plasma membrane Ca-ATPase or Na,K-ATPase. The interaction of thapsigargin with the SERCA isoforms is rapid, stoichiometric, and essentially irreversible. These properties demonstrate that thapsigargin interacts with a recognition site found in, and only in, all members of the endoplasmic and sarcoplasmic reticulum calcium pump family.
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PMID:Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps. 183 68

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

The rate of calcium uptake and the level of calcium accumulation was measured in cardiac muscle SR from hibernating and nonhibernating Richardson's ground squirrels. In whole heart homogenates, the rate of calcium uptake was higher (P less than 0.05) in hibernating animals than it was in active animals. Further purification of homogenates into sacroplasmic reticulum (SR) preparations showed that the hibernating animals had the highest rate of calcium uptake and the greatest level of calcium accumulation. These results could not be explained by variations in non-SR membrane contaminants nor by changes in the maximal activity or total amount of a SR marker enzyme, the Ca(2+)-ATPase. The addition of ryanodine to the calcium uptake medium increased the level of calcium accumulation in all groups by a similar amount. It is concluded that the high rate of calcium uptake by isolated cardiac SR vesicles from hibernating ground squirrels reflects the activity of the organelle in vivo, and that the ability of the ryanodine-insensitive population of SR vesicles to accumulate calcium is affected by hibernation.
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PMID:Seasonal variations in the rate and capacity of cardiac SR calcium accumulation in a hibernating species. 183 35

Several studies have demonstrated that physiological aging significantly affects cardiovascular function. Experimental researches, conducted on cardiac muscle of senescent animals, have shown a prolongation of both contraction and relaxation times. This phenomenon was explained by a reduced Ca(++)-stimulated ATPase pump activity, responsible for the reduced sarcoplasmic reticulum Ca++ uptake rate. The myofilament response to Ca++ in the aging heart is normal as are peak contractile force production and post-extrasystolic twitch potentiation during continual paired stimulation. On the other hand, the inotropic response to cardiac glycosides and beta-adrenoceptor stimulation is diminished in senescent compared to adult myocardium. This decreased contractility could result mainly from mechanisms controlling Ca++ reuptake from sarcoplasmic reticulum and relaxation time (diastolic phase) rather than those determining force generation and contraction time (systolic phase). Age-related physiologic structural changes are not associated with significant variations in left ventricular diastolic and systolic sizes, but they seem a direct consequence of the rising systolic blood pressure observed in these age decades. Myocardial hypertrophy should not be considered a specific marker of the senescent heart, but rather an adaptive response to increased afterload conditions. As regard the relationship between age and diastole, it is important to underline that the alterations in aging cardiac muscle function primarily involve the isovolumic relaxation time and diastolic phase. With age, the early diastolic phase declines while the contribution of atrial contraction to ventricular diastolic filling increases as well as the isovolumic relaxation time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Aging and left ventricular diastolic function]. 184 77


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