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)

Effect of verapamil on the organic acid transport was examined with rat kidney cortical slices. Verapamil increased the initial rate of p-aminohippurate (PAH) uptake, markedly enhanced its maximal accumulation under steady-state conditions and depressed the efflux of PAH. The accumulation of urate was also stimulated by verapamil. D600, a derivative of verapamil, showed the same effect as verapamil with regard to the stimulation of PAH accumulation. Kinetic studies revealed that verapamil resulted in an increase in the Vmax of the transport of PAH. The apparent Km remained essentially constant. The PAH accumulation was enhanced by aerobic preincubation of the slices with verapamil at 37 degrees C. On the other hand, the preincubation of the slices with verapamil at 0 degrees C did not alter the PAH accumulation. Oxygen consumption and ATP content in the slices and microsomal (Na+ + K+)adenosine triphosphatase activity were not affected by verapamil. Verapamil enhanced a Na+ gradient to some degree. however, the PAH accumulation in the presence of verapamil and ouabain was increased approximately the same amount as in the absence of these drugs regardless of the dissipation of the Na+ gradient by ouabain. These results suggest that verapamil accumulated by the slices stimulates the PAH uptake and its stimulatory action cannot be explained by the increase in the Na+ gradient and stimulation of (Na+ + K+)adenosine triphosphatase activity.
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PMID:Stimulatory action of verapamil on transport of organic acids in rat kidney cortical slices. 621 70

Thyroid status was altered by use of a low-iodine-perchlorate (PC) regimen and either reversal with NaI or injections of L-3,5,3'-triiodothyronine (T3). The PC regimen decreased renal and hepatic oxygen consumption (QO2), alpha-glycerophosphate dehydrogenase (alpha-GPDH), and Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) to comparable extents (25 vs. 23%, 26 vs. 39%, and 41 vs. 51%, respectively). Administration of T3 to hypothyroid rats elicited dose-dependent increases in hepatic and renal cortical QO2, ouabain-sensitive oxygen consumption (QO2(t)), alpha-GPDH, and Na-K-ATPase activities. The half-maximal increases in all of the response parameters in both kidney and liver were obtained at dosages of 6-32 micrograms T3/100 g body wt. The equivalences in the renal cortical vs. hepatic responses were indicated by correlation coefficients of approximately 0.97. Kidney and liver nuclei also showed similar high-affinity binding of 125I-T3-K1/2 = 29 vs. 18 micrograms T3/100 g body wt, and Nmax = 1.8 vs. 2.1 ng T3/mg DNA. The patterns of the responses plotted as a function of T3 occupancy of the high-affinity nuclear binding sites were indistinguishable in kidney and liver. These results imply similar modes of action of T3, probably initiated at the nuclear level, in both kidney and liver.
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PMID:Nuclear binding of T3 and effects of QO2, Na-K-ATPase, and alpha-GPDH in liver and kidney. 625 44

Cellular oxygen consumption was monitored during stimulation and inhibition of the Na+- and K+-dependent adenosine triphosphatase in a suspension of intact tubules isolated from the rabbit renal cortex. Respiratory rates were compared to the ADP-stimulated respiratory rate (state 3 rate) obtained in mitochondria released directly from the renal tubules by digitonin shock. At 37 degrees C, in the presence of NADH-linked substrates and fats, isolated renal cells respire at 50 to 60% of the state 3 rate. Inhibition of the (Na+,K+)-ATPase with the cardiac glycoside, ouabain, results in a decline in respiration to 25 to 30% of the state 3 rate. Stimulation of the (Na+,K+)-ATPase produced as a result of nystatin-mediated dissipation of plasma membrane Na+ and K+ gradients results in increased respiration with an oxygen consumption rate characteristic of optimal ATP synthesis (state 3). The relationship between metabolic substrate regimen, mitochondrial respiratory capacity, and cellular energy demand is examined in the context of these findings.
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PMID:Mitochondrial respiratory capacity and Na+- and K+-dependent adenosine triphosphatase-mediated ion transport in the intact renal cell. 627 Jan 7

The effects of thyroid hormone treatment on brown adipose tissue (BAT) and liver metabolism were assessed by measuring oxygen consumption, sodium-potassium adenosine triphosphatase (Na-K-ATPase), and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activities in tissues from triiodothyronine- (T3) and vehicle-injected (for 3 days) newborn and adult rabbits. In the newborns, basal BAT cellular respiration was increased [mean (%/- SE) = 119 +/- 18 vs. 65 +/- 4 microliter O2/10(6) cells-1 . h in controls (P less than 0.005)], whereas hepatic respiration was unchanged. Ouabain had no effect on basal BAT cellular respiration, but suppressed hepatic respiration by 30% in both newborn groups. T3 treatment had no effect on NE- (10(-6) M) stimulated BAT respiration, whereas adult hepatic respiration was increased almost twofold. alpha-GPD activities were increased in both newborn BAT and adult liver but not in newborn liver. Na-K-ATPase activity was significantly increased only in newborn liver. In conclusion, 1) both BAT and liver are thyroid-hormone sensitive in the newborn rabbit, but the responses to T3 treatment are different in the two tissues; 2) the failure to stimulate both hepatic alpha-GPD and respiration in the newborn appears to be a developmental phenomenon characteristic of the rabbit; 3) thyroid hormones have little effect on sodium transport-dependent respiration in either BAT of liver in the newborn rabbit.
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PMID:Thyroid hormone-sensitive brown adipose tissue respiration in the newborn rabbit. 627 13

Cumulative addition of vanadate or ouabain to rat liver perfusions giving perfusate concentrations up to about 500 microM revealed that both liver hemodynamics and bile production are influenced by these substances, but their ways of action differed markedly. Vanadate increased hepatic vascular resistance in a dose-dependent manner with an apparent Km of 30 microM. Not until vanadate concentrations in perfusate reached 60 to 70 microM did the hepatic oxygen consumption decrease significantly together with a decrease in bile flow. Ouabain at perfusate concentrations up to nearly 300 microM caused only a slight fall in perfusate flow, a dose-dependent slight fall in oxygen uptake and a dose-dependent, marked increase in bile flow. Further addition of even small amounts of ouabain initiated a marked fall in perfusate flow, oxygen uptake and bile production and appeared to induce maldistribution of intrahepatic perfusate flow. The vasoconstrictive effect of vanadate was not influenced by alpha or beta blockers, atropine or blockers of Ca++-transport, whereas the effect of ouabain could be strongly reduced by phenoxybenzamine or verapamil. Vanadate-induced vasoconstriction may be caused by an inhibition of smooth muscle Ca++-adenosine triphosphatase and ouabain may induce vasoconstriction by inhibiton of smooth muscle Na, K-adenosine triphosphatase. The hepatic uptake and excretion of ouabain may explain the choleresis observed at small perfusate concentrations of ouabain. Inhibition of bile production at higher concentrations of ouabain and vanadate could be secondary to simultaneous changes in liver hemodynamics.
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PMID:Comparison of vanadate and ouabain effects on liver hemodynamics and bile production in the perfused rat liver. 627 35

The effect of both exogenous and endogenous changes in thyroid status on in vitro tissue respiration and thermogenic enzymes (sodium-potassium-adenosine triphosphatase and alpha-glycerophosphate dehydrogenase) was studied in fetal and newborn sheep. Oxygen consumption of liver and brain increased from 25 +/- 4.1 and 58.5 +/- 2.8 microliters O2 X 100 mg-1 X h-1, respectively, in tissues from unthyroidectomized fetal animals at 136-140 days gestation to 60 +/- 4.2 and 72 +/- 1.5 microliters O2 X 100 mg-1 X h-1 in tissues from unthyroidectomized newborn lambs between birth and 7 days of age. The physiological changes in thyroid function that normally occur at birth resulted in a mean (+/- SE) plasma triiodothyronine (T3) concentration of 563 +/- 39 ng/dl in the newborn lambs compared with 39 +/- 8 ng/dl in the fetal animals. Kidney respiration and thermogenic enzyme activities in the several tissues studied did not change. Liver, kidney, and brain respiration and thermogenic enzymes from T3-treated thyroidectomized fetal and newborn lambs were not increased (compared with untreated thyroidectomized animals) despite a marked increase in plasma T3 concentrations. Conclusions are that 1) liver, kidney cortex, and frontal brain cortex in the fetal and newborn lamb are relatively insensitive to the calorigenic effect of thyroid hormones, and 2) a perinatal increase in hepatic and cerebral respiration occurs in newborn animals (compared with fetal animals) but is probably not due solely to perinatal increases in thyroid hormones.
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PMID:Effect of changes in thyroid status on tissue respiration in fetal and newborn sheep. 630 3

The effect of timolol on the active transport system in the iris root-ciliary body of rabbits was studied to elucidate the action mechanism of timolol. Neither Na+-K+-adenosine triphosphatase (ATPase) nor Mg++-ATPase was inhibited by timolol at 1 X 10(-4) M concentration. None of the energy production parameters (oxygen consumption, glucose metabolism, and lactic acid formation) was inhibited by timolol either. Further, the biosynthesis of prostaglandins E2 and F2 alpha was not affected by timolol at 1 X 10(-3) M. The blood flow to the eye was measured with a 85Sr-microsphere method. It was found that the blood flow in the iris root-ciliary body and choroid was significantly reduced by a topical application of 0.25% timolol. The dopamine concentration in the iris root-ciliary body was reduced by timolol at 1 X 10(-5) M concentration. Neither epinephrine nor norepinephrine concentration was altered by timolol. The results indicate that timolol reduces the rate of aqueous humor formation through reduction of blood flow to the ciliary process rather than via the inhibition of the active transport system or that of prostaglandin biosynthesis.
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PMID:Action mechanism of timolol to lower the intraocular pressure in rabbits. 631 18

The concept of a hypermetabolic state to explain metabolic tolerance to ethanol grew from the recognition that the rate of alcohol metabolism is, in general, limited by the rate at which mitochondria can reoxidize reducing equivalents and thus by the rate at which oxygen can be consumed by the liver. This relationship appears to be most important in conditions in which the alcohol dehydrogenase (ADH)/QO2 ratio is high and is not in conflict with observations suggesting that ADH can, under certain conditions, constitute a rate-determining step for ethanol metabolism in rodents. Liver preparations from animals fed alcohol chronically, in which an increase in ethanol metabolism is shown, consume oxygen at higher rates. This effect, concerning which there is discrepancy among investigators, depends on the type of preparation. Thyroid hormones play a permissive role in the development of the hypermetabolic state, while increased circulating levels of these hormones are not required. Antithyroid drugs inhibit both metabolic tolerance in vivo and the hypermetabolic state. While the hypermetabolic state requires an increased ATP utilization in the form of an adenosine triphosphatase, or an inhibition of ATP synthesis, the different mechanisms proposed for such an effect do not quantitatively account for the increases in oxygen consumption. In humans and animals chronically exposed to ethanol, but withdrawn, oxygen tensions in blood leaving the liver are significantly reduced. In some situations, low oxygen tensions in zone 3 of the hepatic acinus can reach critical hypoxic levels and may lead to cell necrosis. Studies in which the effectiveness of propylthiouracil is tested in human alcoholic hepatitis are discussed.
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PMID:Hypermetabolic state and hypoxic liver damage. 632 88

The bioflavinoid quercetin was found to exert at least three separate effects on human polymorphonuclear leukocytes. (1) Concentrations of approximately 100 microM inhibited the membrane-associated magnesium adenosine triphosphatase by 60%-80% in either broken cell preparations or intact cells. Lineweaver-Burk plots showed the inhibition to be uncompetitive in nature. (2) Similar concentrations of quercetin inhibited respiratory burst activity of the cells as measured by oxygen consumption, glucose oxidation, or iodination of protein. All inhibitions were dose-dependent and were observed with either opsonized zymosan or phorbol myristate acetate as stimulus. (3) Quercetin likewise inhibited the transport of the nonmetabolizable hexose, 3H-2-deoxyglucose. These observations are most consistent with the hypothesis that quercetin exerts a generalized effect at the level of the cell membrane of the neutrophil.
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PMID:Effects of quercetin on magnesium-dependent adenosine triphosphatase and the metabolism of human polymorphonuclear leukocytes. 645 Jun 23

An initial event in gram-negative bacteremia is activation of the complement cascade with production of C5a. C5a, in turn, acts as a chemotactic stimulus for leukocytic aggregation and, in conjunction with bacterial products, stimulates the release of oxygen free radicals from leukocytes. We have hypothesized that these oxygen free radicals (.O2-, superoxide anion; .OH, hydroxyl radical; H2O2, hydrogen peroxide) contribute to the characteristic myocardial dysfunction of endotoxin shock, Isolated canine cardiac sarcoplasmic reticulum (SR) was used as a subcellular determinant of mechanical function. SR was incubated for 20 min at 37 degrees C in the presence of phorbol myristate acetate activated leukocytes (A-L) and calcium uptake and Ca2+-adenosine triphosphatase (ATPase) activities were measured. Activated leukocytes significantly depressed SR Ca2+ uptake rates (C = 1.12 +/- 0.05 mumol CA2+/mg-min; A-L = 0.73 +/- 0.05). The addition of catalase (CAT; 10 micrograms/ml) or superoxide dismutase (SOD: 10 micrograms/ml) plus CAT reversed the inhibition of SR Ca2+ uptake. SOD further depressed SR Ca2+ uptake (+SOD = 0.55 +/0 0.04 mumol Ca2+/mg-min). Mannitol had no effect. SR ATPase activity was inhibited with A-L (C = 1.41 +/- 0.04 mumol Pi/mg-min; A-L = 0.84 +/- 0.09). Neither mannitol, nor SOD nor CAT alone had any effect on the depression of SR ATPase activity. SOD plus CAT reversed the ATPase depression induced by A-L. It is concluded that phorbol myristate acetate activated leukocytes via free radical-mediated mechanisms can directly affect function and activity of the excitation-contraction coupling system of cardiac muscle. Free radical scavengers identified hydrogen peroxide as a major mediator of depressed Ca2+ uptake rates. In conjunction with the superoxide anion, hydrogen peroxide contributes to the depressed ATPase activity.
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PMID:Interaction of oxygen free radicals and cardiac sarcoplasmic reticulum: proposed role in the pathogenesis of endotoxin shock. 685 Oct 3


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