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)

In hypokalaemia the incidence of cardiac toxicity with digitalis is increased, possibly through changes in the affinity or capacity of the digitalis receptor in the heart. Previous studies have reported an increased ouabain binding capacity or Na+-K+ ATPase activity after hypokalaemia in human erythrocytes and rabbit and guinea pig hearts and no change or decreases in rabbit or rat skeletal muscles with no changes in ouabain affinity. The present study determined (a) the effect of potassium on 3H-ouabain binding to normokalaemic guinea pig cardiac cell membranes, (b) the effect of acute hypokalaemia induced by a potassium deficient diet for 14-18 days in guinea pigs on 3H-ouabain binding to erythrocytes and cardiac and skeletal muscle homogenates, and (c) ouabain induced inotropy in isolated contracting guinea pig left atria, right ventricular papillary muscles, and soleus muscle strips from normokalaemic and hypokalaemic guinea pigs. 3H-ouabain binds to cardiac cell membranes in the presence of magnesium and inorganic phosphate with an affinity (KD value) of 1.13 X 10(-7) mol X litre-1. Potassium decreased this affinity without changing the binding capacity. Erythrocytes and heart muscle homogenates showed the same affinity as cardiac cell membranes, whereas soleus muscle homogenates had a higher affinity for ouabain (KD 5.1 X 10(-8) mol X litre-1). After hypokalaemia, the ouabain affinity did not change in any tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovasc Res 1986 Apr
PMID:Ouabain binding and inotropy in acute potassium depletion in guinea pigs. 371 9

To investigate the effects of sodium-potassium activated adenosine triphosphatase inhibition on central cardiovascular regulation a microinjection of ouabain was given into the hypothalamus of urethane anaesthetised rats. Doses of 0.01-1.0 micrograms per rat injected into the posterior hypothalamus produced a rise in blood pressure within 1 min, the maximum rise occurring 15-20 min later in a dose dependent manner. Both heart rate and abdominal sympathetic nerve activity increased with the rise in blood pressure. Ouabain injected into either the anterior preoptic hypothalamus or the ventromedial hypothalamus produced no notable cardiovascular responses. These results suggest that an endogenous digitalis like substance produced in the hypothalamus as a result of sodium loading may participate in central cardiovascular regulation by increasing sympathetic outflow in the discrete area of the brain, as does ouabain.
Cardiovasc Res 1986 Apr
PMID:Cardiovascular and sympathetic responses to ouabain injected into the hypothalamus in rats. 371 10

The action potential duration (APD) was measured using an Ag-AgCl electrode, in open chest anaesthetised dogs (n = 8) and puppies, 4 to 6 months old (n = 8), with complete atrio-ventricular dissociation and beta-adrenergic blockade. They were paced in the control period at a frequency of 120 beats . min-1. Both adults and puppies showed maximum action potential duration at a test pulse interval of over 700 ms. Below this the adult dogs showed a progressive shortening of the action potential duration (mean APD 81.5% at 200 ms). In contrast, the puppies showed much less shortening (91% at 200 ms; p less than 0.001). Measurements of Na+, K+-ATPase activity by the Rb uptake method gave values of 13.4 +/- 1.3 (puppies, n = 4) and 6.1 +/- 1.1 (adults, n = 6). These results may be consistent with the idea of a greater influx and efflux of sodium in the myocardial cells of the puppy compared with the adult dog.
Cardiovasc Res 1985 Nov
PMID:On the change of cardiac action potential with age: a study in dogs. 407 57

The purpose of this study was to identify alterations in specific enzyme and Ca2+ binding activities in cardiac sarcolemmal fractions from UM-X7.1 myopathic Syrian hamsters during the development of cardiomyopathy. Experimental and healthy control animals were examined from 25 to 200 days of age. Sarcolemmal Na+, K+-ATPase activity was depressed in the myopathic hamsters throughout the time course of this study. Sarcolemmal ATP-independent Ca2+ binding was found to be depressed in experimental animals as early as 55 days of age. Ca2+ -stimulated, Mg2+ -dependent ATPase activity was depressed in the experimental animals by 90 days of age and this decrease in enzyme activity was accompanied by a decrease in ATP-dependent Ca2+ binding capacity of the sarcolemmal membranes. Mg2+ -ATPase and Ca2+ -ATPase activities were only affected in the latter stages of the disease (155 to 200 days old). NaF, epinephrine and Gpp(NH)p stimulation of the sarcolemmal adenylate cyclase activity was also observed to be attenuated during the latter stages of the disease. These defects in adenylate cyclase system of the sarcolemmal fraction appeared specific since basal adenylate cyclase activity was not altered at any age studied. The results demonstrate that the earliest lesions in sarcolemmal activity in myopathic hamster heart occur in Na+, K+-ATPase and ATP-independent Ca2+ binding capacity. These defects correspond temporally to the initial stages of cardiac necrotic development in this strain of myopathic hamster.
Cardiovasc Res 1984 Sep
PMID:Sarcolemmal alterations during the development of genetically determined cardiomyopathy. 614 91

Possible enhancement by free fatty acids (FFA) of the arrhythmogenic actions of ouabain was studied in rabbits. The mean dose of ouabain required for inducing ventricular tachycardia or fibrillation in conscious animals was significantly lowered by intravenous injection of 5 ml of a 20% fat emulsion (Lipofundin), which significantly elevated circulating FFA. Lipofundin alone did not initiate arrhythmias in another group of animals. The transmembrane action potential duration (APD) and the maximum rate of depolarization (Vmax)recorded from rabbit papillary muscles were markedly reduced under the influence of 2 mM octanoate, a short-chain FFA. Ouabain, 10(-7M), reduced significantly only the APD measured at zero level of repolarization. In papillary muscles exposed to both octanoate and ouabain, resting potential, overshoot, APD, and Vmax were all significantly decreased below control values. The synergistic arrhythmogenic actions of FFA and ouabain might be explained by the inhibiting effect of both agents on membrane (Na+ + K+)ATPase.
J Cardiovasc Pharmacol 1980
PMID:Enhancement of ouabain arrhythmias by fatty acids. 615 30

The distribution of 3H-digoxin has been measured in a large number of tissues from the central, autonomic, and peripheral nervous system after the induction of ventricular tachycardia by infusing digoxin into anesthetized dogs. In most parts of the nervous system the tissue digoxin concentration was close to that in the cerebrospinal fluid. Digoxin accumulation in the choroid plexus probably represented a labeling of adenosine triphosphatase. There was a markedly higher concentration of digoxin in the neurohypophysis than in the adenohypophysis, and the very high levels in the neurohypophysis are hard to explain. There may be a relationship between the pituitary and the hypothalamic digoxin levels, although the concentration in the latter was unimpressive. The fornix showed a modest increase in 3H-digoxin concentration and may play a role, as its efferent discharge goes to the hypothalamus. The high concentration of digoxin in the area postrema suggests that this central nervous system structure is responsible, at least in part, for producing digoxin-induced cardiac arrhythmias. It may act as a sensing organ sensitive to blood digoxin concentration. Either it is the only central nervous structure implicated, or it is involved together with the fornix-hypothalamus-hypophysis pathways. Further proof is given for the importance of the autonomic nervous system in cardiac arrhythmias by the high digoxin levels in the superior cervical sympathetic ganglion and adrenal medulla.
J Cardiovasc Pharmacol
PMID:3H-digoxin distribution in the nervous system in ventricular tachycardia. 617 30

Ethacrynic acid (ECA) was used to study the relationship between ion transport and alpha-adrenergic activation of glycogenolysis in perfused rat livers. ECA alone enhanced glycogenolysis and produced a massive loss of K+ from the liver. These effects were partially blocked by dithioerythritol. ECA suppressed the metabolic responses to phenylephrine and the alpha-adrenergic redistribution of ions. Ouabain-sensitive and ouabain-insensitive ATPase of isolated liver plasma membranes were inhibited and binding of [3H]epinephrine to alpha-adrenergic sites was decreased by ECA. It is concluded that in liver ECA acts at three different sites by blocking SH groups: active ion transport across the plasma membrane, alpha-adrenoreceptors, and phosphorylase phosphatase.
J Cardiovasc Pharmacol 1982
PMID:Effects of ethacrynic acid on the alpha-adrenergic control ov hepatic glycogenolysis. 617 48

The basic polypeptide ATX II (MW 4,770) isolated from the sea anemone Anemonia sulcata evokes a pronounced and dose-dependent positive inotropic effect in different mammalian heart preparations. The mechanism of this effect is so far unknown. (a) Investigations on isolated guinea pig atria indicate that changes of the steady state cellular Na, K and Ca concentrations cannot account for the positive inotropic effect. (b) An increase of the surface pressure of phospholipid monolayers was observed only at cardiotoxic ATX II concentrations. However, the 45Ca binding to phosphatidylserine, as the essential Ca-binding phospholipid, was not changed even at cardiotoxic ATX II concentrations. (c) Neither the enzymatic activity nor the ouabain inhibition kinetic of an isolated Na/K-ATPase preparation was affected by ATX II. (d) In intact electrically stimulated (1 Hz) guinea pig atria the binding of [3H]ouabain increases by about 50% at a positive inotropic ATX II concentration. The results suggest that the positive inotropic effect of ATX II is not caused by an unspecific membrane damaging action or by a direct interaction with the Na/K-ATPase. The increased binding of [3H]ouabain to intact heart muscles indirectly reflects an increased pump activity of the Na/K-ATPase, which is caused by an elevated Na transient due to the electrophysiologically well-established mechanism of the ATX II action on fast Na channel, i.e., delayed inactivation of the fast Na flux. However, the exact mechanism of the ATX II induced positive inotropic effect remains unknown.
J Cardiovasc Pharmacol
PMID:Studies on the mechanism of the positive inotropic effect of ATX II (Anemonia sulcata) on isolated guinea pig atria. 617 2

MDL 17,043 (1,3-dihydro-4-methyl-5-[4-(methylthio)-benzoyl]-2H-imidazol-2-one) is a new drug with cardiotonic properties. Its effects on several biochemical systems considered to be important in myocardial contraction were investigated and compared with those produced by amrinone and theophylline. Dog cardiac phosphodiesterases (PDEs) were separated into three major forms and labeled PDE I, II, and III according to the order of elution during isolation by column chromatography. PDE I and II, considered to be "high-Km" enzymes for cyclic AMP, were not inhibited by MDL 17,043, amrinone, or theophylline in concentrations of 50 microM. PDE III, a "low-Km" enzyme, was strongly inhibited by MDL 17,043. Kinetic studies showed the inhibition to be characteristic of partial competitive inhibition. At 0.25 microM cyclic AMP, 1.3 microM MDL 17,043 caused 50% inhibition of PDE III (I50), while the I50 for amrinone and theophylline were estimated to be 19.5 microM and 119 microM, respectively. Dog kidney Na+, K+-ATPase was inhibited 54% by 100 microM MDL 17,043 while amrinone caused an 18% inhibition at the same concentration. Ca2+-ATPase and Ca2+ uptake by dog sarcoplasmic reticulum vesicles were unchanged by MDL 17,043 concentrations up to 300 microM and 100 microM, respectively. It is suggested that the inhibition of PDE III is related to the cardiotonic effects produced by MDL 17,043 and amrinone, although inhibition of Na+, K+-ATPase may also play a role at high concentrations of these drugs.
J Cardiovasc Pharmacol
PMID:Biochemical studies on the mechanism of cardiotonic activity of MDL 17,043. 617 50

Several Ca channel blockers--verapamil, nifedipine, nimodipine (Bay e 9736), and nitrendipine (Bay e 5009)--had different effects on Ca transport by sarcoplasmic reticulum vesicles from either skeletal or cardiac muscle. Both nimodipine and nitrendipine (1 X 10(-4) M) stimulated Ca sequestration in the absence of a Ca-precipitating anion by either cardiac or skeletal sarcoplasmic reticulum (SR), with nitrendipine being the more potent stimulator. Nifedipine (1 X 10(-4)M) had no significant effect, whereas at higher concentrations (3 X 10(-3) M) verapamil inhibited the Ca sequestration reaction. Nitrendipine stimulated Ca ATPase and Ca sequestration to a similar extent. Stimulation of Ca sequestration by nitrendipine was dependent on drug/membrane phospholipid mole ratios of between 1:4 and 3:1, as well as absolute drug concentration thus suggesting an interaction of the drug with membrane phospholipids. Nifedipine, nitrendipine, nimodipine, and verapamil (1 X 10(-4)M) had no effect on phosphate-supported Ca uptake by skeletal SR, whereas higher concentrations of verapamil (3 X 10(-3)M) inhibited this reaction by either cardiac or skeletal SR. The results of this study suggest that (a) Ca channel blockers have complex and variable effects on SR membranes, (b) these effects are similar in cardiac and skeletal SR, and (c) the effects are in part mediated through an interaction with membrane phospholipids or hydrophobic portions of the Ca ATPase.
J Cardiovasc Pharmacol
PMID:Effects of Ca channel blockers on Ca transport and Ca ATPase in skeletal and cardiac sarcoplasmic reticulum vesicles. 618 85


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