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ATP plays a role in neurite stimulation with activated mast cells.: J Neuroimmunol, Vol. 192, No. 1-2. (December 2007), pp. 49-56.Previous ly, we showed that nerve-mast cell cross-talk can occur bidirectionall y and that substance P is a mediator to activate mast cells. Here, we have studied the mediators to activate nerves cocultured with mast cells. Addition of antigen to the cocultures of superior cervical ganglia (SCG) and rat basophilic leukemia cells (RBLs) elicited Ca(2+) response in RBLs and after a lag period induced Ca(2+) signal in SCG neurites. Pyridoxalphosp hate-6-azophen yl-2',4'-disul fonic acid (purinergic receptor antagonist) or apyrase (ATP-hydrolyzi ng enzyme) reduced the Ca(2+) signals in neurites, indicating that ATP released from activated mast cells was one of important mediators to activate nerves.R Suzuki, T Furuno, K Okamoto, R Teshima, M Nakanishi

Source: J Neuroimmunol, Vol. 192, No. 1-2. (December 2007), pp. 49-56.
Adenosine and Adenosine Receptors in the Pathomechanism and Treatment of Respiratory Diseases.: Current medicinal chemistry, Vol. 15, No. 9. (2008), pp. 917-922.It has been known for a long time that inhaled adenosine-mono phosphate (AMP) induces airway obstruction in asthmatic patients, but not in healthy subjects. The mechanism of AMP is indirect and occurs via its decay product, adenosine. It stimulates mast cells through its low-affinity receptor A2B to release histamine, which ultimately leads to smooth muscle contraction. This feature of adenosine reveals its pro-inflammato ry function, which may play important role in asthma. Indeed, mice lacking adenosine deaminase (ADA), an enzyme which decomposes adenosine, develop asthma-like disorder with elevated IgE, eosinophilia and airway hyperresponsiv eness. Human studies showed elevated adenosine levels in bronchoalveola r lavage and exhaled breath condensate of asthmatics as compared to healthy people. Furthermore, certain human ADA phenotypes are associated with prevalence of asthma. These data suggest a protective role for ADA and a pro-inflammato ry function for adenosine in asthma. The role of adenosine in inflammatory processes, however, is not unequivocal. Some in vitro studies showed that adenosine binding to its high-affinity receptor A2A results in inhibition of leukotriene synthesis or function of adhesion molecules. It is possible that the concentration of adenosine in lung tissues determines whether it promotes or reduces inflammation. Adenosine has also been associated with other respiratory diseases such as fibrosis, sarcoidosis, cystic fibrosis or tuberculosis. Identification of adenosine receptor subtypes and their role in the pathomechanism of respiratory diseases may provide new therapeutical targets. This review aims to summarize the role of adenosine and adenosine receptors in asthma and other pulmonary disorders.G Vass

Source: Current medicinal chemistry, Vol. 15, No. 9. (2008), pp. 917-922.
ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication.: Mol Cell, Vol. 16, No. 6. (22 December 2004), pp. 967-978.The origin recognition complex (ORC) is a six-subunit, ATP-regulated, DNA binding protein that is required for the formation of the prereplicative complex (pre-RC), an essential replication intermediate formed at each origin of DNA replication. In this study, we investigate the mechanism of ORC function during pre-RC formation and how ATP influences this event. We demonstrate that ATP hydrolysis by ORC requires the coordinate function of the Orc1 and Orc4 subunits. Mutations that eliminate ORC ATP hydrolysis do not support cell viability and show defects in pre-RC formation. Pre-RC formation involves reiterative loading of the putative replicative helicase, Mcm2-7, at the origin. Importantly, preventing ORC ATP hydrolysis inhibits this repeated Mcm2-7 loading. Our findings indicate that ORC is part of a helicase-loadi ng molecular machine that repeatedly assembles Mcm2-7 complexes onto origin DNA and suggest that the assembly of multiple Mcm2-7 complexes plays a critical role in origin function.JL Bowers, JC Randell, S Chen, SP Bell

Source: Mol Cell, Vol. 16, No. 6. (22 December 2004), pp. 967-978.
Clostridium pasteurianum F1Fo ATP Synthase: Operon, Composition, and Some Properties: J. Bacteriol., Vol. 185, No. 18. (15 September 2003), pp. 5527-5535.The atp operon encoding F1Fo ATP synthase in the fermentative obligate anaerobic bacterium Clostridium pasteurianum was sequenced. It consisted of nine genes arranged in the order atpI(i), atpB(a), atpE(c), atpF(b), atpH(delta), atpA(alpha), atpG(gamma), atpD(beta), and atpC(varepsilo n), which was identical to that found in many bacteria. Reverse transcription- PCR confirmed the presence of the transcripts of all nine genes. The amount of ATPase activity in the membranes of C. pasteurianum was low compared to what has been found in many other bacteria. The F1Fo complexes solubilized from membranes of C. pasteurianum and Escherichia coli had similar masses, suggesting similar compositions for the F1Fo complexes from the two bacteria. Western blotting experiments with antibodies raised against the purified subunits of F1Fo detected the presence of eight subunits, alpha, beta, gamma, delta, varepsilon, a, b, and c, in the F1Fo complex from C. pasteurianum. The F1Fo complex from C. pasteurianum was activated by thiocyanate, cyanate, or sulfhydryl compounds; inhibited by sulfite, bisulfite, or bicarbonate; and had tolerance to inhibition by dicyclohexylca rbodiimide. The target of thiol activation of the F1Fo complex from C. pasteurianum was F1. Thiocyanate and sulfite were noncompetitive with respect to substrate Mg ATP but competitive with respect to each other. The F1 and Fo parts of the F1Fo complexes from C. pasteurianum and E. coli bound to each other, but the hybrid F1Fo complexes were not functionally active.Amaresh Das, Lars Ljungdahl

Source: J. Bacteriol., Vol. 185, No. 18. (15 September 2003), pp. 5527-5535.
Relationship between Growth Rate and ATP Concentration in Escherichia coli: A BIOASSAY FOR AVAILABLE CELLULAR ATP: J. Biol. Chem., Vol. 279, No. 9. (27 February 2004), pp. 8262-8268.Prev ious studies showed that adenosine triphosphate (ATP) concentrations in Escherichia coli changed during certain growth transitions and directly controlled the rate of rRNA transcription initiation at those times. The relationship between ATP concentration and rRNA transcription during steady-state growth is less clear, however. This is because two commonly employed methods for measuring ATP concentrations in bacteria, both of which rely on physical extraction followed by chromatographi c separation of small molecules, resulted in dramatically different conclusions about whether ATP concentration changed with steady-state growth rate. Extraction with formic acid indicated that ATP concentration did not change with growth rate, whereas formaldehyde treatment followed by extraction with alkali indicated that ATP concentration increased proportionally to the growth rate. To resolve this discrepancy, we developed a bioassay for ATP based on the expression of a variant of the firefly luciferase enzyme in vivo and measurement of luminescence in cells growing in different conditions. We found that the available ATP concentration did not vary with growth rate, either in wild-type cells or in cells lacking guanosine 5'-diphosphate , 3'-diphosphate , providing insight into the regulation of rRNA transcription. More broadly, the luciferase bioassay described here provides a general method for evaluating the ATP concentration available for biochemical processes in E. coli and potentially in other organisms. 10.1074/jbc.M3 11996200David Schneider, Richard Gourse

Source: J. Biol. Chem., Vol. 279, No. 9. (27 February 2004), pp. 8262-8268.
Transcription Regulation by Initiating NTP Concentration: rRNA Synthesis in Bacteria: Science, Vol. 278, No. 5346. (19 December 1997), pp. 2092-2097.10.1 126/science.27 8.5346.2092Tam as Gaal, Michael Bartlett, Wilma Ross, Charles Turnbough, Richard Gourse

Source: Science, Vol. 278, No. 5346. (19 December 1997), pp. 2092-2097.
Invariance of the Nucleoside Triphosphate Pools of Escherichia coli with Growth Rate: J. Biol. Chem., Vol. 275, No. 6. (11 February 2000), pp. 3931-3935.The ATP and GTP pools of Escherichia coli have recently been reported to increase approximately 10-fold with increasing growth rates in the range from 0.4 to 1.4 generations/ho ur (Gaal, T., Bartlett, M. S., Ross, W., Turnbough, C. L., and Gourse, R. L. (1997) Science 278, 2092-2097). Moreover, it was proposed that this variation of the nucleotide pools, particularly the ATP pool, might be responsible for the well known growth rate-dependent regulation of rRNA synthesis in E. coli. To test this hypothesis we have measured the nucleoside triphosphate pools as a function of growth rate for several E. coli strains. We found that the size of all four RNA precursor pools are essentially invariant with growth rate, in the range from 0.5 to 2.3 generations/ho ur. Nevertheless we observed the expected growth rate-dependent increase of RNA accumulation in these strains. In light of these results, it seems unlikely that nucleotide pool variations should be responsible for the growth rate-dependent regulation of rRNA synthesis. 10.1074/jbc.27 5.6.3931Carste n Petersen, Lisbeth Moller

Source: J. Biol. Chem., Vol. 275, No. 6. (11 February 2000), pp. 3931-3935.
Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.: Circ Res, Vol. 79, No. 2. (August 1996), pp. 208-221.The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to electrophysiol ogical changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations , only approximately 0.6% of the KATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-ATP channels should play a significant role in action potential shortening during hypoxic/ischem ic episodes, with the fraction of open channels involved being very low ( < 1%). However, the results of the model suggest that activation of IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischem ic situations.JM Ferrero, J Sáiz, JM Ferrero, NV Thakor

Source: Circ Res, Vol. 79, No. 2. (August 1996), pp. 208-221.
Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges: Proceedings of the National Academy of Sciences, Vol. 95, No. 9. (28 April 1998), pp. 5009-5014.10.1 073/pnas.95.9. 5009Masashi Isshiki, Joji Ando, Risa Korenaga, Hiroshi Kogo, Toyoshi Fujimoto, Toshiro Fujita, Akira Kamiya

Source: Proceedings of the National Academy of Sciences, Vol. 95, No. 9. (28 April 1998), pp. 5009-5014.
Endothelial nitric oxide synthase and calcium production in arterial geometries: an integrated fluid mechanics/cell model.: Journal of biomechanical engineering, Vol. 130, No. 1. (February 2008)It is well known that atherosclerosi s occurs at very specific locations throughout the human vasculature, such as arterial bifurcations and bends, all of which are subjected to low wall shear stress. A key player in the pathology of atherosclerosi s is the endothelium, controlling the passage of material to and from the artery wall. Endothelial dysfunction refers to the condition where the normal regulation of processes by the endothelium is diminished. In this paper, the blood flow and transport of the low diffusion coefficient species adenosine triphosphate (ATP) are investigated in a variety of arterial geometries: a bifurcation with varying inner angle, and an artery bend. A mathematical model of endothelial calcium and endothelial nitric oxide synthase cellular dynamics is used to investigate spatial variations in the physiology of the endothelium. This model allows assessment of regions of the artery wall deficient in nitric oxide (NO). The models here aim to determine whether 3D flow fields are important in determining ATP concentration and endothelial function. For ATP transport, the effects of a coronary and carotid wave form on mass transport is investigated for low Womersley number. For the carotid, the Womersley number is then increased to determine whether this is an important factor. The results show that regions of low wall shear stress correspond with regions of impaired endothetial nitric oxide synthase signaling, therefore reduced availability of NO. However, experimental work is required to determine if this level is significant. The results also suggest that bifurcation angle is an important factor and acute angle bifurcations are more susceptible to disease than large angle bifurcations. It has been evidenced that complex 3D flow fields play an important role in determining signaling within endothelial cells. Furthermore, the distribution of ATP in blood is highly dependent on secondary flow features. The models here use ATP concentration simulated under steady conditions. This has been evidenced to reproduce essential features of time-averaged ATP concentration over a cardiac cycle for small Womersley numbers. However, when the Womersley number is increased, some differences are observed. Transient variations are overall insignificant, suggesting that spatial variation is more important than temporal. It has been determined that acute angle bifurcations are potentially more susceptible to atherogenesis and steady-state ATP transport reproduces essential features of time-averaged pulsatile transport for small Womersley number. Larger Womersley numbers appear to be an important factor in time-dependent mass transfer.A Comerford, MJ Plank, T David

Source: Journal of biomechanical engineering, Vol. 130, No. 1. (February 2008)

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