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At least 415 records · Page 23Linked to original sources
PubMed1985

Evidence for vagal involvement in the electrophysiologic actions of exogenous adenosine and adenosine triphosphate in the canine heart.

A closed chest canine model was used to study the electrophysiologic effects of adenosine and adenosine triphosphate (ATP) on the sino-atrial (SA) and atrioventricular (AV) nodes. Exogenous adenosine and ATP, when rapidly administered into the right atrium, caused transient negative chronotropic and dromotropic effects on the SA and AV nodes, respectively. These effects reached a maxima in 10-15 sec and dissipated in less than 120 sec. The electrophysiologic effects of ATP were more pronounced than those of adenosine. Physostigmine enhanced the chronotropic effects of adenosine and ATP and the dromotropic effects of ATP. Atropine abolished the enhancement of the electrophysiologic effects of adenosine and ATP caused by physostigmine. In the pentobarbital anaesthetized dog, ATP triggers a vagal reflex which plays a major role in mediating its electrophysiologic effects. Vagal involvement in the electrophysiologic action of adenosine is more modest, but does not appear to be mediated via reflex mechanisms.

Adenosine↗
PubMed1999

Adenosine triphosphate: established and potential clinical applications.

Adenosine 5'-triphosphate (ATP) is a purine nucleotide found in every cell of the human body. In addition to its well established role in cellular metabolism, extracellular ATP and its breakdown product adenosine, exert pronounced effects in a variety of biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation and liver glycogen metabolism. These effects are mediated by both P1 and P2 receptors. A cascade of ectonucleotidases plays a role in the effective regulation of these processes and may also have a protective function by keeping extracellular ATP and adenosine levels within physiological limits. In recent years several clinical applications of ATP and adenosine have been reported. In anaesthesia, low dose adenosine reduced neuropathic pain, hyperalgesia and ischaemic pain to a similar degree as morphine or ketamine. Postoperative opioid use was reduced. During surgery, ATP and adenosine have been used to induce hypotension. In patients with haemorrhagic shock, increased survival was observed after ATP treatment. In cardiology, ATP has been shown to be a well tolerated and effective pulmonary vasodilator in patients with pulmonary hypertension. Bolus injections of ATP and adenosine are useful in the diagnosis and treatment of paroxysmal supraventricular tachycardias. Adenosine also allowed highly accurate diagnosis of coronary artery disease. In pulmonology, nucleotides in combination with a sodium channel blocker improved mucociliary clearance from the airways to near normal in patients with cystic fibrosis. In oncology, there are indications that ATP may inhibit weight loss and tumour growth in patients with advanced lung cancer. There are also indications of potentiating effects of cytostatics and protective effects against radiation tissue damage. Further controlled clinical trials are warranted to determine the full beneficial potential of ATP, adenosine and uridine 5'-triphosphate.

Adenosine Diphosphate↗
PubMed1989

Electrophysiological effects of adenosine and adenosine triphosphate on sheep Purkinje fibres under normal and simulated ischaemic conditions.

1. The electrophysiological effects of adenosine and adenosine triphosphate (ATP) were examined in sheep Purkinje fibres, superfused in vitro with either a normal or a hypoxic, hyperkalaemic and acidotic physiological salt solution (PSS). The ability of adenosine to modify the effects of noradrenaline on action potential characteristics was also investigated. 2. The only statistically significant effects of adenosine (10(-6)-10(4) M) and of ATP (10(-6)-10(-4) M) on normal action potential characteristics were a slight dose-dependent shortening of the action potential by adenosine and a depolarization by ATP, 10(-4) M. 3. Superfusion with a hypoxic, hyperkalaemic and acidotic PSS caused marked reductions in resting membrane potential, upstroke and duration of the action potential. 4. Both adenosine and ATP attenuated the reduction in the rate of rise of the upstroke and the amplitude of the action potential caused by the modified PSS. 5. Adenosine did not alter the noradrenaline-induced effects on automaticity or on action potentials of normal or depressed Purkinje fibres. 6. Adenosine and ATP had electrophysiological effects on Purkinje fibres, exposed to conditions in vitro that mimic mild myocardial ischaemia, that were different from those observed on normally polarized fibres.

Action Potentials↗
PubMed1966

Adenosine triphosphate: protection against radiation-indued chromosome loss in Drosophila.

Injection of 5 milligrams of adenosine triphosphate per milliliter into adult Drosophila melanogaster X(e2) yB/sc(8) y(+) 4 to 8 hours old either immediately before or after administration of 2000 roentgens of x-rays protected those cells in spermatogenesis which were in or near meiosis from the loss of the ring X or the y(+) portion of Y chromosome. The loss of the chromosomes was determined by appearance of exceptional XO males in the offspring.

Adenosine Triphosphate↗
PubMed1975

Evidence for enhanced uptake of adenosine triphosphate by muscle of animals in shock.

Although it has been shown that infusion of adenosine triphosphate (ATP)-magnesium chloride (MgCl2) proved beneficial in the treatment of shock, it is not known whether this effect is due to improvement in the microcirculation or to direct provision of energy. In searching for the mechanism of this, we have now examined the in vitro uptake of ATP by soleus muscle of animals in shock. Rats were bled to a mean arterial pressure of 40 mm. Hg and so maintained for 2 hours. Following death the two soleus muscles from each animal were removed and incubated in Krebs-HCO3 buffer containing 10 mM. of glucose, 5 mM. (8--14C) of ATP, 5 mM. (8--14C) of ADP, or 0.5 mM. (8--14C) of adenosine, and 5 mM. of MgCl2 for 1 hour under an atmosphere of 95 percent O2 to 5 percent CO2. Following homogenization and centrifugation, samples of the muscle extract and the medium were subjected to electrophoresis to separate the various nucleotides. The concentrations of the several nucleotides in medium and muscle were calculated from the radioactivity observed in each fraction. The uptake of 14-C-ATP by muscles from animals in shock was three times greater than was the uptake by control muscles. This leads us to conclude that the beneficial effect of ATP-MgCl2 to animals in shock could be due to provision of energy directly to tissues in which ATP levels were lowered.

Achilles Tendon↗
PubMedDate not supplied

Cellular and biophysical evidence for interactions between adenosine triphosphate and P-glycoprotein substrates: functional implications for adenosine triphosphate/drug cotransport in P-glycoprotein overexpressing tumor cells and in P-glycoprotein low-level expressing erythrocytes.

P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated with the expression of Pgp are in any way coupled. We have measured the stoichiometry of transport coupling between drug and ATP release. The drug and ATP transport that is inhibitable by the sulfonylurea compound, glyburide (P. E. Golstein, A. Boom, J. van Geffel, P. Jacobs, B. Masereel, and R. Beauwens, Pfluger's Arch. 437, 652, 1999), permits determination of the transport coupling ratio, which is close to 1:1. In view of this result, we asked whether ATP interacts directly with Pgp substrates. We show by measuring the movement of Pgp substrates in electric fields that ATP and drug movement are coupled. The results are compatible with the view that substrates for Pgp efflux are driven by the movement of ATP through electrostatic interaction and effective ATP-drug complex formation with net anionic character. This mechanism not only pertains to drug efflux from tumor cells overexpressing Pgp, but also provides a framework for understanding the role of erythrocytes in drug resistance. The erythrocyte consists of a membrane surrounding a millimolar pool of ATP. Mammalian RBCs have no nucleus or DNA drug/toxin targets. From the perspective of drug/ATP complex formation, the RBC serves as an important electrochemical sink for toxins. The presence in the erythrocyte membrane of approximately 100 Pgp copies per RBC provides a mechanism for eventual toxin clearance. The RBC transport of toxins permits their removal from sensitive structures and ultimate clearance from the organism via the liver and/or kidneys.

ATP Binding Cassette Transporter, Subfamily B, Mem↗