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

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty-seven isolated, blood perfused, continuously weighed canine hearts have been utilized to study the development of abnormal myocardial fluid retention during early myocardial ischemic injury. Inflatable balloon catheters were positioned around the left anterior descending coronary arteries (LAD) of 54 hearts or the proximal left circumflex coronary arteries of three hearts for study of the following intervals of coronary occlusion: a) 10 minutes followed by 20 minutes of reflow, b) 40 minutes followed by either no reflow or by 20 minutes of reflow, and c) 60 minutes without reflow. After 60 minutes of fixed coronary occlusion, histologic and ultrastructural examination revealed mild swelling of many ischemic cardiac muscle cells in the absence of interstitial edema, cardiac weight gain, and obvious structural defects in cell membrane integrity. After 40 minutes of coronary occlusion and 20 minutes of reflow, significant cardiac weight gain occurred in association with characteristic alterations in the ischemic region, including widespread interstitial edema and focal vascular congestion and hemorrhage and swelling of cardiac muscle cells. Focal structural defects in cell membrane integrity were also noted. The development of abnormal myocardial fluid retention after 40 minutes of LAD occlusion occurred in association with a significant reduction in sodium-potassium-ATPase activity in the ischemic area, but with no significant alteration in either creatine phosphokinase or citrate synthase activity in the same region. Despite the abnormal myocardial fluid retention in these hearts, it was possible pharmacologically to vasodilate coronary vessels with adenosine and nitroglycerin infusion to maintain a consistently high coronary flow following release of the coronary occlusion after 40 minutes and to even exceed initial hyperemic flow values following release of the occlusion when adenosine and nitroglycerin infusion was delayed until 15 minutes after reflow. Thus, the data indicate that impaired cell volume regulation and interstitial fluid accumulation and focal structural defects in cell membrane integrity are early manifestations of ischemic injury followed by reflow, but fail to establish a major role for the abnormal fluid retention in altering coronary blood flow prior to the development of extensive myocardial necrosis. In contrast, fixed coronary occlusion for 60 minutes results in mild intracellular swelling but no significant interstitial edema and no obvious structural defects in cell membrane integrity.
...
PMID:Abnormal myocardial fluid retention as an early manifestation of ischemic injury. 13 29

Trapymin (TM) relaxed excised renal, coronary, pulmonary, femoral and mesenteric arteries and this relaxation was not antagonized by propranolol. The dose-response curve of TM was parallel to that of nitroglycerin and papaverine and steeper than that of dipyridamol or adenosine. TM exerted inotropic and chronotropic actions on excised rat atrium. TM was also effective through the oral route and the effectiveness tended to decrease slightly after repeated use for ten days. TM was effective on vasopressin induced angina in rats and electrocoagulation-induced myocardial infarction. TM suppressed adrenaline-induced arrhythmia but not CaCl2-induced arrhythmia. TM reduced catecholamine content in brain, adrenals and heart but had no influence on monoamine oxidase or dopamine-beta-hydroxylase. TM revealed ganglion-blocking and neuron-blocking actions in cervical ganglion in cats. With propranolol, TM-induced hyperglycemia and reduction in glycogen content in liver and heart was antagonized but TM-induced rise in free fatty acid in serum was not antagonized. Na+-K+ dependent ATPase of bovine heart and P/O ratio of mitochondria of rat heart was not influenced by TM. ADP-induced aggregation of platelets was antagonized by TM. These data indicate that TM induced coronary dilation is partly due to a papaverine like action and also to ganglion-blocking, neuron-blocking and anti-adrenergic action. On the other hand, TM possessed catecholamine release and cardiotonic action as related to beta-receptors.
...
PMID:[Pharmacology of cornary dilator agent, trapymin. (2) Analysis of its mode of action]. 124 70

1. Experiments were designed to determine the effect of inhibition of Na+, K+ ATPase by ouabain, Na(+)-free and K(+)-free solutions on the relaxations induced by nitric oxide, nitroglycerin and sodium nitroprusside in coronary smooth muscle. 2. Rings without endothelium of canine left anterior descending coronary artery were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution, in the presence of indomethacin, propranolol, and phenoxybenzamine. The rings were incubated with ouabain, Na(+)-free or K(+)-free solutions prior to contractions with prostaglandin F2 alpha. 3. Nitric oxide induced transient relaxations which were significantly depressed by ouabain but were not affected by Na(+)- or K(+)-free solutions. Thus, the inhibitory effect of ouabain on relaxations to nitric oxide is not due to inhibition of the Na+, K+ pump. 4. The relaxation induced by sodium nitroprusside was impaired both in the presence of ouabain and after incubation in Na(+)- or K(+)-free solution, suggesting that it may involve in part activation of Na+, K+ pumping. 5. Only high concentration of ouabain and Na(+)-free solution decreased the relaxation evoked by nitroglycerin, indicating that the mechanism of action of nitroglycerin on vascular smooth muscle does not involve the Na(+)-K+ pump.
...
PMID:Ouabain, Na(+)-free and K(+)-free solutions and relaxations to nitric oxide and nitrovasodilators. 164 45

The reflex control of the circulation is clearly abnormal in heart failure. It has been known for many years that the baroreflex control of heart rate is depressed in both humans and animals with heart failure. The mechanisms for these abnormalities have not been well worked out. We have carried out experiments to determine the relative roles of the various components involved in the arterial baroreflex arc which may be abnormal in chronic heart failure. An experimental model of chronic heart failure was used which involved continuous ventricular pacing in dogs for periods of up to 6 weeks. This model is characterized by progressive increases in left atrial and left ventricular enddiastolic pressure with increases in resting heart rate and decreases in mean arterial pressure. The dogs become edematous, showing both pulmonary and peripheral edema and ascites. Exercise tolerance is also reduced. Three sets of experiments are described. In the first study, the activity from arterial baroreceptors was recorded in normal dogs and in dogs with heart failure. Carotid sinus pressure-receptor discharge curves were constructed along with pressure-diameter curves. Increasing carotid sinus pressure using either static or pulsatile pressure steps from below threshold to saturation levels caused an increase in discharge at each step. The curves generated in each group of dogs showed that the baroreceptor discharge sensitivity was significantly depressed in the dogs with heart failure. The peak slope of the curves as well as the threshold were significantly different from the normal dogs. There were no differences in carotid sinus compliance curves between the two groups of dogs. Perfusion of the carotid sinus with a dose of ouabain which did not constrict the carotid sinus (0.01 micrograms/ml) caused a shift in the pressure-discharge curve back to that seen in normal dogs. This dose of ouabain did not affect discharge sensitivity in normal dogs. These data suggest that an augmentation of Na-K ATPase in baroreceptor nerve endings in heart failure contributes to the poor discharge sensitivity. In the second series of experiments, the baroreflex control of heart rate was evaluated in dogs before and after heart failure had been induced. Both reflex tachycardia (in response to nitroglycerin) and reflex bradycardia (in response to phenylephrine) were depressed in dogs with heart failure. The use of cholinergic and beta adrenergic blocking drugs indicated that both arms of the autonomic control of the heart were partly responsible for this depressed chronotropic response.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Modulation of baroreflex and baroreceptor function in experimental heart failure. 178 63

First, we will briefly describe how our study on the mechanisms of relaxant effects of nitroglycerin and related compounds (NG) on the vascular smooth muscle developed to a study on the sarcolemmal (SL) Ca(2+)-ATPase. These compounds were found to have no effects on the voltage-dependent Ca2+ channel and Ca(2+)-induced Ca2+ release from the sarcoplasmic reticulum (SR) and Na(+)-Ca2+ exchange mechanism has been shown not to play an important role in the vascular smooth muscle. Furthermore, when we initiated our study, the idea of receptor-operated Ca2+ channels and Ca2+ release from the SR by inositol triphosphates were not known. A major part of this review is devoted to a description of the characteristic features of SL Ca(2+)-ATPase and its regulation by various protein kinases. References to SR enzyme are made when necessary. Brief mention is made of the putative molecular structure and its possible variations as envisaged by genetic engineering techniques. However, particular attention is directed to the regulation by cyclic GMP-dependent protein kinase as this seems to be most important as regards the mechanisms of vascular smooth muscle relaxation by NG.
...
PMID:[Studies on plasmalemmal Ca(2+)-pump ATPase--for a better understanding of the mechanisms of relaxation of smooth muscle]. 183 35

Sarcoplasmic reticulum (SR) vesicles were incubated with azido derivatives of Cascade blue (ACB), Lucifer yellow (ALY), 2,7-naphthalene-disulfonic acid (ANDS), and fluorescein (AF) for 0.1-24 h at 2 degrees C. All four dyes gave intense reaction with the cytoplasmic domain of the Ca(2+)-ATPase on photoactivation after brief incubation. The penetration of the dyes into the luminal space of the SR was determined after centrifugation through Sephadex microcolumns to remove the external dye, followed by photolabeling and gel electrophoresis of the photolabeled proteins. The reaction of ACB and ANDS with the Ca(2+)-ATPase and with calsequestrin increased progressively during incubation up to 24 h indicating their slow accumulation in the luminal space, while ALY and AF did not show significant penetration into the vesicles. The distribution of the covalently attached ACB in the Ca(2+)-ATPase was tested by tryptic proteolysis after labeling exclusively from the outside (OS), from the inside (IS) or from both sides (BS). In all cases intense ACB fluorescence was seen in the A fragment with inhibition of ATPase activity. In the OS preparations the A1, while in IS the A2 fragment was more intensely labeled. There was no significant incorporation of ACB into the region of B fragment identified by FITC fluorescence. The crystallization of the Ca(2+)-ATPase by EGTA + decavanadate was completely inhibited in the BS samples after labeling either in the Ca2E1 or E2V conformation. There was no inhibition of crystallization in the OS preparations. In the IS preparations labeled in the Ca2E1 state the crystallization was impaired, while in the E2V state there was only slight disorganization of the crystals. The total amount of ACB photoincorporated into SR proteins after incubation for 24 h was 1.75 nmol/mg protein; 2/3 of this labeling occurred from the outside and 1/3 from the inside. Similar level of labeling was obtained in media that stabilize the E1 or the E2 conformation of the Ca(2+)-ATPase.
...
PMID:Covalent labeling of the cytoplasmic or luminal domains of the sarcoplasmic reticulum Ca(2+)-ATPase with fluorescent azido dyes. 183 61

A Ca2(+)-ATPase with a high affinity for free Ca2+ (apparent Km of 0.13 microM) was found and characterized in membrane fractions from porcine aortic and coronary artery smooth muscles in comparison with the plasma membrane Ca2(+)-pump ATPase purified from porcine aorta by calmodulin affinity chromatography. The activity of the high-affinity Ca2(+)-ATPase became enriched in a plasma membrane-enriched fraction, suggesting its localization in the plasma membrane. The enzyme was fully active in the absence of exogenously added Mg2+, but required a minute amount of Mg2+ for its activity as evidenced by the findings that it was fully active in the presence of 0.1 microM free Mg2+ but lost the activity in a reaction mixture containing trans-cyclohexane-1,2-diamine-N,N,N',N'-tetraacetic acid as a divalent cation chelator which has, unlike EGTA, high affinities for both Ca2+ and Mg2+. It was able to utilize a variety of nucleoside di- and triphosphates as substrates, such as ADP, GDP, ATP, GTP, CTP, and UTP, showing a broad substrate specificity. The activity of the enzyme was not modified by calmodulin (5, 10 micrograms/ml). Trifluoperazine, a calmodulin antagonist, had a partial inhibitory effect on the activity at 30 to 240 microM, but this inhibition could not be reproduced by a more specific calmodulin antagonist, W-7, indicating that this inhibition by trifluoperazine was not specific. Furthermore, the high-affinity Ca2(+)-ATPase activity was not modified either by low concentrations (0.5-9 microM) of vanadate or by 1-100 microM p-chloromercuribenzoic acid. Cyclic GMP, nitroglycerin, and nicorandil did not have any effect on the enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:A Ca2(+)-activated, Mg2(+)-dependent ATPase with high affinities for both Ca2+ and Mg2+ in vascular smooth muscle microsomes: comparison with plasma membrane Ca2(+)-pump ATPase. 196 53

Measurements of ion transport across isolated lingual epithelium of rat were correlated with electrophysiological recordings from taste nerves. At hyperosmotic concentrations of NaCl, sodium ions enter the mucosal membrane of the isolated epithelium partially through an amiloride-inhibitable pathway and exit the serosal membrane through a Na+-K+-ATPase. At hyposmotic concentrations of KCl, potassium ions enter the mucosal membrane through a K+ pathway that is inhibited by 4-aminopyridine and exit at the serosal membrane through a K+ pathway that is inhibited by BaCl2. The inhibition of sodium transport by amiloride and potassium transport by 4-aminopyridine is consistent with previously published electrophysiological recordings from the chorda tympani nerve bundle (CT) and recordings from nucleus of the solitary tract (NST) obtained here. The responses to NaCl are greater than the responses to KCl at equimolar concentrations over the entire concentration range both in epithelial and neural measurements. At hyposmotic concentrations of NaCl the epithelial responses include inward sodium and outward chloride components. Isolated rat tongue is only slightly stimulated by D-glucose or sucrose as are the CT and NTS responses. These data suggest that events in taste transduction can be understood, in part, by measuring the epithelial responses of isolated rat tongue.
...
PMID:Transport pathways in rat lingual epithelium. 283 49

The effects of the antianginal drugs nitroglycerin, nicorandil, diltiazem, verapamil and nicardipine on the activity of calcium-stimulated magnesium-dependent ATPase (Ca2+-ATPase) were investigated in the microsomal fraction from porcine coronary artery smooth muscle cells. Two discrete Ca2+-dependent ATPase components were observed: [1] a high affinity component, which was a specific Ca2+-ATPase, [with a half saturation constant for Ca2+ (Km) of 0.44 microM, and maximum velocity (Vmax) of 124.3 pmol of phosphate (Pi) released/micrograms of protein/30 min]: [2] a low affinity component in which Ca2+ could be replaced by Mg2+ without loss of its activity. Nitroglycerin and nicorandil (1 microM and 10 microM) both stimulated the activity of the Ca2+-ATPase significantly [142 +/- 12 (mean +/- standard error), and 137 +/- 10% of the control with nitroglycerin, and 152 +/- 17 and 135 +/- 20% with nicorandil] at a Ca2+ concentration of 0.3 microM. Diltiazem, verapamil and nicardipine did not cause significant stimulation. Nitroglycerin and nicorandil (1 microM), significantly decreased the Km for Ca2+ from the control value of 0.44 +/- 0.06 microM to 0.26 +/- 0.03 and 0.22 +/- 0.03 microM, respectively. Nitroglycerin and nicorandil may dilate coronary arteries by stimulating this Ca2+ extrusion pump enzyme through reduction of intracellular Ca2+ in smooth muscle cells.
...
PMID:Effects of nitrates and calcium channel blockers on Ca2+-ATPase in the microsomal fraction of porcine coronary artery smooth muscle cells. 296 38

The amount of phosphoric acid liberated from ATP by Ca2+ (Mg2+)-ATPase in microsomal fraction of guinea-pig thoracic aorta decreased with decreasing concentrations of calcium ions from 20.0 to 2.5 mM in the mixture of the enzyme and substrate. When CaCl2 (2.5 mM) and MgCl2 (5.0 mM) were present in the substrate, both nitroglycerin (0.1 to 1.0 mM) and SIN-1 A (a molsidomine derivative, 0.05 to 1.0 mM) increased the liberated phosphoric acid in a concentration-dependent manner. The contractile tension of smooth muscle prepared from guinea-pig thoracic aorta, which was previously increased by the pretreatment with prostaglandin F2 alpha (5.0 microM), was relaxed by both nitroglycerin and SIN-1 A (0.01 to 100 microM each) in a concentration-dependent manner. From the results, it is assumed that the stimulation of Ca2+ (Mg2+)-ATPase [Ca2+-pump ATPase] activity induced by nitroglycerin and SIN-1 A in the microsome of thoracic aorta takes part in the relaxation of contractile tension in the tissue.
...
PMID:Increase in Ca2+ (Mg2+)-ATPase activity induced by a molsidomine derivative (SIN-1 A) and nitroglycerin in microsomal fraction of guinea-pig thoracic aorta. 614 24


1 2 3 Next >>

---