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)

Human red cell membrane Ca2+-stimulatable, Mg2+-dependent adenosine triphosphatase (Ca2+-ATPase) activity and its response to thyroid hormone have been studied following exposure of membranes in vitro to specific long-chain fatty acids. Basal enzyme activity (no added thyroid hormone) was significantly decreased by additions of 10(-9)-10(-4) M-stearic (18:0) and oleic (18:1 cis-9) acids. Methyl oleate and elaidic (18:1 trans-9), palmitic (16:0) and lauric (12:0) acids at 10(-6) and 10(-4) M were not inhibitory, nor were arachidonic (20:4) and linolenic (18:3) acids. Myristic acid (14:0) was inhibitory only at 10(-4) M. Thus, chain length of 18 carbon atoms and anionic charge were the principal determinants of inhibitory activity. Introduction of a cis-9 double bond (oleic acid) did not alter the inhibitory activity of the 18-carbon moiety (stearic acid), but the trans-9 elaidic acid did not cause enzyme inhibition. While the predominant effect of fatty acids on erythrocyte Ca2+-ATPase in situ is inhibition of basal activity, elaidic, linoleic (18:2) and palmitoleic (16:1) acids at 10(-6) and 10(-4) M stimulated the enzyme. Methyl elaidate was not stimulatory. These structure-activity relationships differ from those described for fatty acids and purified red cell Ca2+-ATPase reconstituted in liposomes. Thyroid hormone stimulation of Ca2+-ATPase was significantly decreased by stearic and oleic acids (10(-9)-10(-4) M), but also by elaidic, linoleic, palmitoleic and myristic acids. Arachidonic, palmitic and lauric acids were ineffective, as were the methyl esters of oleic and elaidic acids. Thus, inhibition of the iodothyronine effect on Ca2+-ATPase by fatty acids has similar, but not identical, structure-activity relationships to those for basal enzyme activity. To examine mechanisms for these fatty acid effects, we studied the action of oleic and stearic acids on responsiveness of the enzyme to purified calmodulin, the Ca2+-binding activator protein for Ca2+-ATPase. Oleic and stearic acids (10(-9)-10(-4) M) progressively inhibited, but did not abolish, enzyme stimulation by calmodulin (10(-9) M). Double-reciprocal analysis of the effect of oleic acid on calmodulin stimulation indicated noncompetitive inhibition. Addition of calmodulin to membranes in the presence of equimolar oleic acid restored basal enzyme activity. Oleic acid also reduced 125I-calmodulin binding to membranes, but had no effect on the binding of [125I]T4 by ghosts. The mechanism of the decrease by long chain fatty acids of Ca2+-ATPase activity in situ in human red cell ghosts thus is calmodulin-dependent and involves reduction in membrane binding of calmodulin.
Biochem J 1987 Dec 01
PMID:Action of long-chain fatty acids in vitro on Ca2+-stimulatable, Mg2+-dependent ATPase activity in human red cell membranes. 296 20

Forty kinds of bufotoxins and related compounds were tested for inhibition of Na+, K+ -adenosine triphosphatase from guinea pig heart, and the structure-activity relationship has been discussed. The inhibitory activities of bufotoxins were dependent upon the dicarboxylic acid and amino acid components. The compounds having both the arginine and suberic acid moieties showed the higher inhibitory activities. The sulfates and glucuronides of cardiac steroids exhibited much less potency than the parent genins. The mode of inhibition was determined by means of the Dixon and Lineweaver-Burk plots.
J Pharmacobiodyn 1985 Dec
PMID:Structure-activity relationship of bufotoxins and related compounds for the inhibition of Na+, K+ -adenosine triphosphatase. 300 74

Sodium and potassium ion-transport adenosine triphosphatase from dog kidney was incubated with 0.4-2 mM Ca2+ at 23 degrees C for more than 2 min in the absence of monovalent inorganic cations, cooled to 0 degrees C, and phosphorylated from 1 mM Pi with 2.4 mM MgCl2. The resultant phosphoenzyme resembled that obtained by incubating the enzyme with K+ in place of Ca2+ in six respects. It was concluded that Ca2+ can occupy the monovalent cation-binding center for K+. The rate constant for release of Ca2+ from the dephosphoenzyme at 0 degrees C was 0.17 s-1. The rate of release from the phosphoenzyme was at least 7-fold slower. Phosphorylation stabilized the binding of Ca2+ to the enzyme in contrast to its destabilization of the corresponding K X enzyme complex. K-sensitive phosphoenzyme did not respond to free Ca2+. Thus Ca2+ was not easily accepted by nor released from the phosphoenzyme and would not be an effective substrate for transport. A selective barrier against Ca2+ between the monovalent cation binding center and the extracellular solution is proposed. Release of calcium from the dephosphoenzyme yielded a conformation that was not phosphorylated from Pi. The enzyme changed the conformation of its center for phosphorylation before or at the same time that it changed the conformation of its center for ion transport.
J Biol Chem 1986 Dec 25
PMID:Calcium ion as a probe of the monovalent cation center of sodium, potassium ATPase. 302 76

Human leucocyte sodium pump activity was studied in normal fasting subjects by measuring the ouabain-sensitive 22Na+ efflux rate constants. This 22Na+ efflux rate constant was inversely related to the fasting plasma non-esterified fatty acid level (rs = -0.73, P less than 0.0001). An oral glucose load (40 g/m2 surface area) led to an increase in the leucocyte ouabain-sensitive 22Na+ efflux rate constant after 2 h (1.97 +/- 0.25 to 2.44 +/- 0.19 h-1, P less than 0.0001, n = 11). There was a concomitant fall in the plasma non-esterified fatty acid level. Incubation of leucocytes in vitro with 100 mumol/l linoleic acid inhibited the leucocyte ouabain-sensitive 22Na+ efflux rate constant (1.52 +/- 0.27 vs 0.84 +/- 0.24 h-1, P less than 0.001, n = 8). The leucocyte Na+,K+-dependent adenosine triphosphatase (Na+,K+-ATPase) activity was inhibited in vitro by long chain non-esterified fatty acids, especially when unsaturated. Non-esterified fatty acids may account for some of the Na+,K+-ATPase inhibitory activity of plasma.
Clin Sci (Lond) 1986 Dec
PMID:Non-esterified fatty acids may regulate human leucocyte sodium pump activity. 302

Total injury in ischemic skeletal muscle is a function of ischemic damage and reperfusion injury. In an attempt to decrease reperfusion injury, we gave the oxygen-derived free radical scavengers allopurinol, superoxide dismutase, or mannitol during reperfusion of canine gracilis muscle made ischemic for 4 hours. We measured muscle O2 consumption (MVO2), and tissue calcium, water, and adenosine triphosphatase (ATP) before ischemia, after ischemia, and at 5 minutes and 60 minutes of reperfusion. The results at 60 minutes showed no improvement in MVO2 or ATP. In fact, ATP was significantly depressed with allopurinol and superoxide dismutase treatment, and tissue edema did not decrease in any of the groups. We conclude that the simple addition of oxygen-derived free radical scavengers during the initial reperfusion of totally ischemic skeletal muscle does not attenuate reperfusion injury.
Am Surg 1988 Dec
PMID:Oxygen-derived free radical scavengers and skeletal muscle ischemic/reperfusion injury. 314 90

Of all tissues of the extremities, muscle is the least tolerant of ischemia. Hypothermia of tissue is considered beneficial for the maintenance of viability of muscle in amputated limbs before surgical replantation, but it has never been established that conventional cooling in an ice bath or its equivalent (temperature of tissue, approximately 1 degree Celsius) is the optimum level of hypothermia for minimizing metabolic derangement in ischemic muscle. In this study, we first defined the time course and level of metabolic derangement of muscle in twenty-eight ischemic hind limbs in cats at 22, 15, 10, 5, and 1 degree Celsius. The levels of adenosine triphosphate and phosphocreatine and the mean intracellular pH of the muscles in the lateral aspect of the thigh in each limb were monitored with phosphorus nuclear magnetic-resonance spectroscopy over time. The excised muscles from six freshly amputated legs of live humans were then similarly studied to determine whether muscles from cats and from humans exhibit comparable bioenergetic responses to hypothermic ischemia. A final series of ten ischemic hind limbs from cats was studied by nuclear magnetic resonance and muscle biopsy for direct biochemical assay of tissue energy metabolites to compare the metabolic benefits of two different methods of preserving limbs: continuous cooling in an ice bath, and a newly devised protocol for the rapid induction and maintenance of so-called intermediate (10 +/- 5 degrees Celsius) hypothermia of tissue. Ischemic skeletal muscle in cats exhibited a paradoxical metabolic response to extreme cold (1 degree Celsius). The rate of metabolic deterioration progressively declined with decreasing temperature of tissue to 10 degrees Celsius. However, at 5 degrees Celsius, no additional benefit was detected, and at 1 degree Celsius, there was a significant acceleration in the rates of degradation of adenosine triphosphate and phosphocreatine and in the production of lactate. The rate of degradation of adenosine triphosphate in human ischemic muscle was also faster at 1 degree Celsius than at 10 degrees Celsius. This paradoxical response is apparently due to a severe inhibition of the calcium pump of the sarcoplasmic reticulum of the muscle cell at temperatures of less than 5 degrees Celsius. The inhibition permits an efflux of calcium to the myofibrils, which stimulates both glycolysis and the degradation of adenosine triphosphate by myofibrillar adenosine triphosphatase.
J Bone Joint Surg Am 1988 Dec
PMID:The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia. 319 76

The contractile properties, morphology, and the distribution of striated muscle fiber types of the external and sphincter (EAS) were determined using axial force measurements, fiber size cross-sectional area measurements, and histochemistry. Electrical stimulation of motor axons in pudendal nerve at supramaximal intensities (10 V, 0.05 ms duration) elicited twitch contractions of EAS. The time to peak force after a single pulse ranged from 37 to 42 ms. The time for relaxation to half-maximal twitch force ranged from 20 to 29 ms. Repetitive stimulation of motor axons (0.1-3.0 Hz) produced potentiation and fatigue of single twitch contractile force, suggesting that the EAS of the cat is comprised predominantly of fast-twitch muscle fibers. Confirmation of skeletal muscle fiber types was determined by histochemistry. Frozen serial cross sections of EAS were incubated to demonstrate succinic dehydrogenase (SDH) and myosin adenosine triphosphatase after alkaline preincubation (pH 10.4). Based on these reactions, muscle fibers were classified as fast glycolytic (FG) (high ATPase, low SDH), fast oxidative-glycolytic (FOG) (high ATPase, high SDH), and slow oxidative (SO) (low ATPase, high SDH). The mean percentage +/- SE of each histochemical type was the following: FG, 73.5 +/- 3.9; FOG, 22.8 +/- 3.7; and SO, 3.7 +/- 0.6. These results indicate that the predominant fiber type for the EAS is FG. The EAS of the cat is considered a nominally fast-twitch muscle.
Am J Physiol 1988 Dec
PMID:Physiological, morphological, and histochemical properties of cat external anal sphincter. 320 71

Quinidine is known to inhibit the renal clearance of digoxin without affecting glomerular filtration rate. The renal interaction between these drugs was investigated by a combination of in vivo and in vitro methods. The uptake of digoxin by brush border membrane vesicles was not affected by quinidine. Similarly, digoxin did not inhibit the uptake of the cation N-methylnicotinamide by these vesicles and did not alter the binding kinetics of digoxin to the Na+, K+-adenosine triphosphatase by the antiluminal membrane vesicles. By using the in vivo multiple indicator dilution technique transtubular transport of digoxin was documented; renal-artery infusion of quinidine did not affect the recovery of digoxin in the renal vein or urine. Clearance studies documented that the decrease in the renal clearance of digoxin is paralleled by a significant fall in renal blood flow evidenced by a decrease in p-aminohippuric acid clearance. It is concluded that quinidine inhibits the renal excretion of digoxin not by competition at the tubular cell membrane level, but rather by decreasing renal blood flow. A parallel decrease in biliary clearance of digoxin is documented and may suggest a similar mechanism.
J Pharmacol Exp Ther 1988 Dec
PMID:Effects of quinidine on the renal tubular and biliary transport of digoxin: in vivo and in vitro studies in the dog. 320 14

The effect of triiodothyronine (T3) on the resting membrane potential was measured in primary cultured rat submandibular gland cells. The resting membrane potential was 29.5 +/- 0.71 mV. The hormone T3, at concentrations of 10(-9) M or greater, hyperpolarized the cells 5.8 mV (p less than 0.05). Hyperpolarization was complete within 24 hours. Ouabain (1 mM) depolarized the cells 5.9 mV. Cells exposed to T3 and ouabain had the same membrane potential as cells treated with ouabain alone. These data suggest that the hyperpolarization observed can be, in part, attributed to triiodothyronine-induced synthesis of (Na-K)-adenosine triphosphatase.
Cell Biol Int Rep 1988 Dec
PMID:Effects of triiodothyronine on resting membrane potential of primary cultured rat submandibular gland cells. 322 76

To establish normal histologic and histochemical data and to determine reference values for fiber type proportions (percentages, mean fiber diameters, atrophy and hypertrophy factors, and variability coefficients), a histochemical study was carried out on intrinsic muscles of the larynx (cricothyroid, cricoarytenoid lateralis, cricoarytenoid dorsalis, and thyroarytenoid muscles) of clinically normal dogs. Using myosin adenosine triphosphatase stain under acidic preincubation (pH 4.3) conditions, 3 histochemical fiber types--1, 2A, and 2C--were recognized. The percentage of type-2C fibers varied from 1 to 2% in thyroarytenoid muscles to approximately 10% in cricoarytenoid lateralis muscles. There was no significant difference in mean diameter between left- and right-side specimens of each muscle for type 1 vs type 2. The largest fibers (mean +/- SD) of both types were observed in the cricothyroid muscles (type 1, 38.19 +/- 7.76 microns; type 2, 43.25 +/- 8.66 microns), and the smallest fibers were found in the thyroarytenoid muscles (type 1, 29.38 +/- 5.12 microns; type 2, 33.84 +/- 6.20 microns). Respective mean diameters of fiber types from cricoarytenoid dorsalis (type 1, 32.05 +/- 5.69 microns; type 2, 38.95 +/- 7.75 microns) and cricoarytenoid lateralis (type 1, 33.75 +/- 5.98 microns; type 2, 37.09 +/- 7.01 microns) muscles were similar. The histographic distribution of fiber type diameters was unimodal in all muscles. In each muscle, the mean fiber diameter of type-2 fibers was greater than that of type-1 fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Vet Res 1988 Dec
PMID:Morphologic and morphometric studies of the intrinsic laryngeal muscles in clinically normal adult dogs. 323 48


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