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PubMed1975

Affinity labelling to - SH groups in adenosine - triphosphate - phosphoribosyl transferase with the dinitrophenyl group from S-dinitrophenyl-6-mercaptopurine-riboside 5'-phosphate.

Adenosine-triphosphate-phosphoribosyl transferase from Escherichia coli reacts with S-dinitrophenyl-6-mercaptopurine-riboside 5'-phosphate. In this reaction the dinitrophenyl group becomes attached to the enzyme, while the nucleotide is split off. Most aliphatic high and low-molecular-weight-SH compounds react with the thioether in the opposite way, i.e. bind the nucleotide and split off dinitrothiophenol. It appears that the dinitrophenyl moiety of the thioether interacts with the enzyme in a specific way, and that this interaction activates the bond between the dinitrophenyl group and the sulfur atom. In support of this it was found that dinitrophenol inhibits the transferase reaction with half maximal effect at 0.4 mM. The inhibition is competitive with ATP. Dinitrophenol also competes with ATP in binding studies.

ATP Phosphoribosyltransferase↗

PubMed1990

Adenosine or adenosine triphosphate for supraventricular tachycardias? Comparative double-blind randomized study in patients with spontaneous or inducible arrhythmias.

The effects of intravenous adenosine and adenosine triphosphate (ATP) were studied in a double-blind randomized study during 68 episodes of supraventricular tachycardia in 39 patients. Adenosine restored sinus rhythm in 20 patients (25 of 27 episodes) and produced atrioventricular block to reveal atrial arrhythmias in nine. ATP restored sinus rhythm in 17 patients (22 of 25 episodes) and revealed atrial tachyarrhythmias in six. In patients receiving both compounds, the effective dosage of adenosine was 3.8 mg and of ATP it was 6.6 mg (p less than 0.05), suggesting molar equipotency. Transient side effects were common, occurring in 81% of episodes with adenosine and in 94% with ATP. Symptom scores (0 to 10) were not significantly different (median score for adenosine was 5, for ATP it was 6). Adenosine and ATP were equally effective for the diagnosis and treatment of supraventricular tachycardias and the incidence and severity of side effects were similar. Adenosine has the advantage of being more stable.

Adenosine↗

PubMed1992

[Changes in myocardial blood flow and systemic hemodynamics during hypotensive anesthesia induced by adenosine triphosphate with or without dipyridamole].

The changes in myocardial blood flow and systemic hemodynamics during hypotensive anesthesia with adenosine triphosphate (ATP) or ATP with dipyridamole (0.5 mg.kg-1) were studied in 20 mongrel dogs anesthetized with 0.7% halothane in 100% oxygen. In both groups, mean arterial blood pressure (MAP) was reduced to 60 mmHg by intravenous administration of ATP. During hypotensive anesthesia, coronary blood flow, myocardial blood flow and cardiac index increased significantly in both groups. Lactic acid and uric acid increased significantly during hypotensive anesthesia in the group 1. Heart rate, MAP, systemic vascular resistance and coronary vascular resistance decreased significantly during hypotensive anesthesia in both groups. Mean pulmonary arterial pressure, pulmonary arterial wedge pressure and central venous pressure showed no significant changes in both groups. Base excess in the group 1 increased markedly compared with the group 2. We conclude that pretreatment with dipyridamole can prevent metabolic acidosis that occurs during hypotensive anesthesia induced by ATP.

Adenosine Triphosphate↗

PubMed2006

DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells.

Although autophagy enhances cell survival in nutrient-deprived cells by increasing adenosine triphosphate (ATP) production, it remains unclear if autophagy functions similarly in cells treated with cytotoxic chemotherapy agents. To address this issue, we measured both the ability of DNA damaging agents (Temozolomide, and Etoposide) to induce an autophagy-dependent production of ATP, and the effects of modulation of autophagy on drug-induced cell death. Both drugs induced an autophagy-associated increase in ATP production in multiple glioma cell lines. The drug-induced ATP surge could not be blocked by glucose starvation, but could be blocked by preincubation with the autophagy inhibitor 3-methyladenine (3-MA), an siRNA targeting beclin 1, or the mitochondrial inhibitor oligomycin. Inhibition of autophagy-induced ATP production increased non-apoptotic cell death associated with micronucleation, while restoration of the 3-MA-inhibited ATP surge by addition of pyruvate suppressed cell death. These results show that DNA damaging agents induce an autophagy-associated ATP surge that protects cells and may contribute to drug resistance.

Adenosine Triphosphate↗

PubMed1969

Micelle formation between 5-hydroxytryptamine and adenosine triphosphate in platelet storage organelles.

As judged by analytical ultracentrifugation, 5-hydroxytryptamine and adenosine-5'-triphosphate form micelles in artificial mixtures and also in storage organelles containing 5-hydroxytryptamine of blood platelets of rabbits. Their average apparent molecular weights depend on the concentration and on the molar ratio of the two constituents. The 5-hydroxytryptamine and adenosine triphosphate of these 5-hydroxytryptamine organelles may be stored in vivo together as micelles with apparent molecular weights of several hundred thousands or more.

Adenosine Triphosphate↗

PubMed1970

Phase separation in solutions of noradrenaline and adenosine triphosphate: influence of bivalent cations and drugs.

1. From aqueous solutions of biogenic amines, such as noradrenaline plus adenosine triphosphate (ATP), a second liquid phase spontaneously separates in the presence of small amounts of bivalent cations such as calcium. This separation is reversible and temperature-dependent; the concentration of amine and ATP in the bottom phase is several times higher than in the supernatant.2. Analytical ultracentrifugation provides evidence that the second phase consists of high molecular weight aggregates of the amine and ATP.3. The separated second phase of the noradrenaline-ATP system dissolves isothermally on addition of tyramine and amphetamine which in vivo are known to liberate biogenic monoamines and which have a low tendency to aggregate with ATP. The apparent molecular weights of noradrenaline-ATP aggregates are decreased by tyramine and amphetamine. Dopamine does not diminish the second phase and it can also form aggregates of high molecular weight with ATP.4. Bivalent cations in high concentrations diminish or abolish the separation of a second phase.5. Small amounts of reserpine affect phase separation.6. It is concluded that the physico-chemical properties of aggregates of biogenic amines with ATP may be of importance for understanding the storage and release of the amines in vivo.

Adenosine Triphosphate↗

PubMed1995

Persisting in vitro actin motility at nanomolar adenosine triphosphate levels: comparison of skeletal and cardiac myosins.

We have previously demonstrated in vitro actin movement at nanomolar adenosine triphosphate (ATP) levels using heavy meromyosin from skeletal muscle. In the present work we tested whether the motility at nonomolar ATP-concentrations could be supported by cardiac myosin as well. Actomyosin (skeletal actin and bovine ventricular myosin) was pretreated in the in vitro motility assay with 1 mM ATP; subsequently, the ATP level was reduced by multiple rigor-solution washes. By the final rigor-solution wash, the ATP concentration, monitored by the luciferin-luciferase assay, dropped to the order of 100 nM. Even at this low ATP level actin-filament movement remained in evidence. This was in marked contrast to the situation where ATP concentration was gradually increased from zero; in the latter, filament movement began only as ATP levels exceeded 1-2 microM. The difference indicates that potential energy is stored during the initial ATP treatment, and utilized later as the free ATP falls below micromolar levels. Although the velocity of cardiac myosin-supported movement was only one fourth of that of skeletal myosin, both myosins supported actin movement down to similar ATP concentrations. The similarity in response of the two myosins to ATP implies a similar degree of potential energy storage. Given the significantly different specific ATPase activities, however, it appears that the mechanism of potential energy storage and release involves factors different from those involved in the release of chemical energy by the myosin ATPase.

Actins↗

PubMed1997

Effects of adenosine triphosphate on ventriculoatrial conduction--usefulness and problems in assessment of catheter ablation of accessory pathways.

The effects of adenosine triphosphate (ATP) on ventriculoatrial (VA) conduction were examined before and after accessory pathway (AP) ablation, with emphasis on assessment of the complication of dual atrioventricular (AV) node pathway. By evaluating the differences in the response to ATP of APs and other pathways, we assessed the usefulness and problems of this method. Of 59 patients who underwent AP ablation, 31 showed pre-excitation and 28 had concealed APs. A dual AV node pathway was found in 9 patients (15.3%) before ablation. After ablation, a dual AV node pathway was newly found in 9 patients. Thus, the total number of patients with a dual AV node pathway was 18 (30.5%). VA conduction over APs was not blocked in 26 of 29 patients, but the remaining 3 APs were blocked transiently by ATP. ATP caused VA block over the AV node in 15 of 16 patients and a dual AV node pathway in all 11 patients. In contrast, VA conduction over the retrograde fast pathway was blocked in 9 of 14 patients with AV node re-entrant tachycardia. ATP has little effect on APs, so observation of the response to ATP provides a more reliable and useful means of evaluating successful ablation. With this method, however, it is important to consider the possibility of the presence of ATP-sensitive APs and ATP-resistant retrograde fast pathways. The influence of ablation-induced injury has not been fully clarified. It is therefore essential to take into account various data, including the comparison between data obtained before and after ablation.

Adenosine Triphosphate↗

PubMed2004

Adenosine triphosphate (ATP) enhances the antitumor effect of etoposide (VP16) in lung cancer cells.

We have previously reported that adenosine triphosphate (ATP) enhances the cytotoxic effects of 4-hydroperoxycyclophosphamide (4HC) on leukemia cells without affecting the normal hematopoietic stem cells. Increased cell membrane permeability induced by ATP may cause high incorporation of 4HC into leukemia cells, ultimately leading to cell death. In the present study, we show that ATP has cytotoxicity against PC14, a lung adenocarcinoma cell line. When PC14 cells were cultured with 1, 3, and 5 mM ATP, colony number significantly decreased to 91.0, 48.8, and 2.3% respectively, compared to untreated controls. Additionally, ATP enhanced the antitumor effects of etoposide (VP16) in PC14 and another lung adenocarcinoma cell line, A549. With 5, 25, and 50 mM VP16, the percentage of colony numbers compared to control was 95.5, 75.8, and 61.3% in PC14 and 86.0, 65.0, and 57.1% in A549 cells, respectively. In the presence of 3 mM ATP, however, the colony number of PC14 was further limited to 49.6, 34.1, and 24.4% of the untreated level in 5, 25, and 50 mM VP16, respectively. When A549 cells were incubated with 1 mM ATP, the proportion of clonogeneic cells significantly fell to 62.5, 41.7, and 31.7% in 5, 25, and 50 mM VP16, respectively. With 3 and 5 mM of ATP, uptake of [3H]VP16 in PC14 cells increased respectively to 8.9- and 14.1-fold of the negative controls. These results suggest that ATP itself has antitumor effects on lung cancer cells and enhances the cytotoxicity of VP16 through the increased uptake of VP16 into the cells. The combined use of ATP and antitumor agents such as VP16 may have the potential to improve the therapeutic index in human lung carcinoma.

Adenocarcinoma↗

PubMed1992

Effect of adenosine triphosphate on the postischemic left ventricular function of the immature myocardium.

In this study, the effect of exogenous adenosine triphosphate (ATP) on the immature myocardium was evaluated. Isolated working neonatal rabbit hearts were perfused aerobically for 15 min with Krebs-Henseleit buffer (KHB) at 37 degrees C, and then arrested with St. Thomas solution (STS) in group 1 and STS containing 500 mumol/L of ATP in group 2 at 4 degrees to 6 degrees C and maintained at 10 degrees to 14 degrees C for 60 min. Hearts were reperfused with KHB aerobically at 37 degrees C for 15 min. Each heart served as its own control before and after arrest. Systolic function was significantly depressed in group 1 compared with group 2. There was a significant decrease in the peak left ventricular (LV) systolic pressure in group 1 (preischemia mean [PIM] 54 mm Hg to postischemia mean [PoIM] 42 mm Hg, Student's t test p = 0.007) than in group 2 (PIM 66 to PoIM 62 mm Hg, p = 0.5). The LV pulse pressure decreased in group 1 (PIM 72 to PoIM 54 mm Hg, p = 0.02) but not in group 2 (PIM 84 to PoIM 86 mm Hg, p = 0.9) and the rate of rise of LV pressure (dP/dT) in group 2 improved (PIM 5718 to PoIM 6926 mm Hg, p = 0.4) compared with group 1 (PIM 7021 to PoIM 4125 mm Hg, p = 0.008). The PoIM LV flow (LVF) was greater in group 2 than group 1 (LVF group 1 = 2.7 ml/min, group 2 = 4.5 ml/min). Diastolic pressures were not significantly different in the two groups. Our findings suggest that the incorporation of ATP in STS has a significant effect in improving postischemic LV systolic function in neonatal rabbit hearts.

Adenosine Triphosphate↗

PubMed2002

Purging in autologous hematopoietic stem cell transplantation using adenosine triphosphate (ATP) and 4-hydroperoxycyclophosphamide (4-HC).

In this study, we show potent in vitro purging induced by adenosine triphosphate (ATP) for leukemic cells. The treatment of murine L1210 leukemic cells with 2mM of ATP in vitro for 3h was able to reduce the number of leukemic clonogenic cells by about one order of magnitude presumably by changing the permeability of the leukemic cell membrane. Furthermore, the incubation of L1210 cells with ATP (2mM) and low dose 4-hydroperoxycyclophosphamide (4-HC, 2 microg/ml) for 3h resulted in at least a four-log reduction of clonogenic L1210 cells. Only a slight degree of toxicity to pluripotent hematopoietic stem cells (CFU-S) was observed in both treatment protocols. To determine the efficacy of pharmacological purging by ATP, we designed a murine system to mimic the conditions expected in the clinical setting of autologous transplantation using simulated partial remission marrow (SPRM) which was prepared by mixing normal marrow cells and L1210 cells at a ratio of 9:1. After the SPRM cells were incubated in vitro at a concentration of 1 x 10(6)/ml with both ATP (2mM) and low dose 4-HC (2 microg/ml) for 3h, 5 x 10(4) of the cells were then injected into lethally irradiated 9 weeks male BDF1 mice. All the mice given untreated-SPRM died of leukemia by day 27, whereas none of the recipients transplanted treated-grafts had died by day 70, thus suggesting that the combination use of ATP and 4-HC may be a potentially effective way to purge leukemic cells in autologous stem cell transplantation. The mechanism of the selective killing of leukemic cells is assumed that 4-HC is effectively incorporated into leukemic cells by increasing the permeability of the cell membrane by ATP. Taken together, this simple and rapid procedure is able to purge leukemic cells from autologous bone marrow grafts.

Adenosine Triphosphate↗

PubMed1990

[Different sensitivity of sinus node and atrioventricular node to adenosine triphosphate].

We showed that higher concentration of adenosine 5'-triphosphate (ATP) was required to prolong the spontaneous cycle length of the sinus node (SN) than that required to prolong the spontaneous cycle length of the atrioventricular node (AVN). Spontaneously beating preparations of SN and AVN of rabbit (n = 8) were superfused with Tyrode solution containing 10(-8)-10(-3)M ATP, and action potential was recorded. The negative chronotropic action of ATP was dependent on the concentration. The required concentration of ATP to prolong spontaneous cycle length significantly (p less than 0.01) was 10(-5)M in SN and 10(-6)M in AVN, respectively. At concentrations higher than 10(-6)M, the degree of prolongation was greater in AVN than in SN (p less than 0.01). 10(-7)M dipyridamole enhanced this effect of ATP, while 10(-4)M theophylline reduced it. Action potential duration of 50% repolarization was not changed significantly in either SN or AVN at concentrations up to 10(-3)M. Maximum diastolic potential (MDP) was hyperpolarized from 10(-8)M to 10(-4) M. Hyperpolarization of MDP induced by ATP was greater in AVN than in SN but it was not statistically significant. MDP was depolarized by 10(-3) M ATP in both SN and AVN. The maximum velocity of depolarization was slightly larger in both SN and AVN as the concentration of ATP was increased in the perfusate. However, it was not statistically significant. 10(-3) M ATP decreased the maximum velocity of depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1985

Effect of adenosine triphosphate on the sensitivity of the nicotinic acetylcholine-receptor in the bullfrog sympathetic ganglion cell.

The effects of adenosine triphosphate (ATP) and related compounds on the sensitivity of the nicotinic acetylcholine (ACh)-receptor of bullfrog sympathetic ganglion cells were analysed electro-physiologically. ATP in concentrations between 0.05 and 2 mM increased the amplitudes of the potentials and currents induced by ACh, and carbachol-induced currents. Compared with ATP, ADP was less potent in producing augmentation of the carbachol-induced current by one order of magnitude. AMP, cyclic AMP and adenosine had no appreciable effect. Analysis of this ATP effect, based on Michaelis-Menten type kinetics, revealed that ATP increased the maximum response (Vmax) of the dose-response curve of ACh currents without an appreciable effect on the affinity (Km) of ACh for its receptor. It is suggested that ATP increased the receptor sensitivity by acting on an allosteric site of the nicotinic ACh receptor-ionic channel complex which, thus, may be linked to an ATP receptor, probably of the P2-receptor type (Burnstock, 1981).

Acetylcholine↗

PubMed1975

Nicotinamide adenine dinucleotide phosphate-converting enzymes and adenosine triphosphate citrate lyase in some tissues and organs of New Zealand obese mice with special reference to the enzyme pattern of the pancreatic islets.

In order to obtain a quantitative estimate of the capacity of the pancreatic islets for provision of cytoplasmic acetyl-coenzyme A and for the turnover of nicotinamide adenine dinucleotide phosphate and its reduced form (NADP+/NADPH), the following enzymes were assayed in islets taken from New Zealand Obese mice: adenosine triphosphate citrate lyase (EC 4.1.3.8), malate dehydrogenase (decarboxylating) (NADP+) (EC 1.1.1.40), glutathione reductase (EC 1.6.4.2) and isocitrate dehydrogenase (NADP+) (EC 1.1.1.42). In addition, the activity of isocitrate dehydrogenase (NAD+) (EC 1.1.1.41) was determined. For comparative purposes the activities in exocrine pancreas, liver, heart muscle, kidney cortex and skeletal muscle were also determined. Specimens of pancreatic islets and the other tissues were microdissected from freeze-dried sections. In comparison with the other tissues, adenosine triphosphate citrate lyase was particularly active in the islets. The NADP+/NAPH-converting enzymes had activities, which suggested a rapid turnover of the islet NADP+/NADPH pool.

ATP Citrate (pro-S)-Lyase↗

PubMed1976

The adenosine triphosphate (ATP) depletion test: comparison with the caffeine contracture test as a method of diagnosing malignant hyperthermia susceptibility.

The adenosine triphosphate (ATP depletion ratio, which is the ratio [ATP] in skeletal muscle equilibrated with carbogen and 4% halothane for 30 minutes divided by [ATP] in skeletal muscle equilibrated with carbogen alone for 30 minutes is less than normal in most but not in all rigid MHS patients. The ratio is normal in non-rigid MHS patients. This diagnostic tool is, therefore, useful in the diagnosis of rigid MH. It is not, however, such a sensitive diagnostic parameter as the caffeine contracture test.

Adenosine Triphosphate↗

PubMed1979

Adenosine triphosphate levels during anaphylactic histamine release in rat mast cells in vitro. Effects of glycolytic and respiratory inhibitors.

The adenosine triphosphate (ATP) content of rat mast cells was studied during and after anaphylactic histamine release. The almost identical time course of ATP decrease from mast cells treated with either glycolytic or respiratory inhibitors supports the view that the ATP depletion was largely related to the histamine release process and not to an uncoupling of oxidative phosphorylation by an increased concentration of cytosol Ca2+. The ATP content of the cells was not restored within the 2 h of observation. No inhibition of lactate production from mast cells exposed to antigen in the presence of respiratory inhibitors and glucose was observed. Based on the lactate production from mast cells, the turnover time of ATP was calculated to be about 3/4 min.

Adenosine Triphosphate↗

PubMed1980

Determination of intracellular adenosine triphosphate for detecting anti-HLA antibody-mediated cytolysis. Introduction to a new method for HLA typing.

Intracellular adenosine triphosphate (ATP) determination appears to be a rapid, and reliable technique for the detection of complement-dependent cytolysis mediated by cytotoxic anti-HLA sera. Only a few minutes after the addition of complement to anti-HLA-coated target lymphocytes, a striking loss of intracellular ATP is observed. The technique can be easily performed with minute amounts of cells, serum, and complement, and exactly following the technical conditions of the standard HLA typing microcytotoxicity test (MCT). One of its main advantages over MCT is that the reading of results can be performed automatically. Since in most tissue typing laboratories all steps preceding the reading of MCT results have already been automated, this method could be of great interest, with a view to permitting the complete automation of HLA typing.

Adenosine Triphosphate↗

PubMedDate not supplied

Adenosine triphosphate stimulates thymidine incorporation but does not promote cell growth in primary cultures of renal proximal tubule cells.

Acute addition of adenosine triphosphate (ATP) stimulated thymidine incorporation in confluent, quiescent primary cultures of rabbit renal proximal tubule cells in a dose-responsive manner. Similar increases in thymidine incorporation was observed with adenosine diphosphate and adenosine monophosphate but not with adenosine. The effect of chronic administration of ATP, however, suppressed cell growth. This suppression appears to be due to an effect of ATP to cause detachment of cells from culture plates, resulting in an increase in thymidine incorporation acutely but in suppression of cell growth chronically. ATP is, therefore, not a direct growth promoter of renal proximal tubule cells in primary culture.

Adenosine↗