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1

Minerals to Dairy Cows with Focus on Calcium and Magnesium Balance  

E-print Network

Minerals to Dairy Cows with Focus on Calcium and Magnesium Balance Cecilia Kronqvist Faculty;Minerals to Dairy Cows with Focus on Calcium and Magnesium Balance Abstract Both clinical and subclinical deficiency of calcium and magnesium may cause problems in dairy cows. Clinical hypocalcaemia most commonly

2

Calcium and magnesium in drinking water and the risk of death from hypertension  

Microsoft Academic Search

Many studies have demonstrated a negative association between blood pressure and calcium and magnesium levels. This report examines whether calcium and magnesium in drinking water are protective against hypertension. All eligible hypertension deaths (2336 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (2336 controls), and the levels of calcium and magnesium in the

Chun-Yuh Yang; Hui-Fen Chiu

1999-01-01

3

Automatic photometric titrations of calcium and magnesium in carbonate rocks  

USGS Publications Warehouse

Rapid nonsubjective methods have been developed for the determination of calcium and magnesium in carbonate rocks. From a single solution of the sample, calcium is titrated directly, and magnesium is titrated after a rapid removal of R2O3 and precipitation of calcium as the tungstate. A concentrated and a dilute solution of disodium ethylenediamine tetraacetate are used as titrants. The concentrated solution is added almost to the end point, then the weak solution is added in an automatic titrator to determine the end point precisely.

Shapiro, L.; Brannock, W.W.

1955-01-01

4

Effects of calcium and magnesium on peripheral nerve conduction.  

PubMed

Divalent cations, such as calcium and magnesium, are constantly present in extracellular compartment of most organisms. Modification of extracellular concentrations of divalent ions causes changes in physiologic functions, such as excitability and conduction of the nerves. The present study was designed to investigate and compare the effects of calcium and magnesium on nerve conduction and lidocaine-induced nerve conduction block. The aim of our study was to contribute to better understanding of physiological and pharmacological roles of divalent cations. Experiments were conducted on the sciatic nerves by using the sucrose-gap recording technique. We evaluated the effects of test solutions containing different calcium or magnesium concentrations, prepared with or without lidocaine, on compound action potentials to determine physiological and pharmacological roles of these cations. After the control recordings, the nerve was exposed to Ringer's solution containing 0, 1.9, 3.8 mM Ca2+ and 1.9 and 3.8 mM Mg2+ with or without 1 mM lidocaine. Decreasing the Ca2+ concentrations in Ringer's solution with or without lidocaine enhanced both tonic and phasic blocks. However, increased Mg2+ concentration did not change the tonic blocks but increased the phasic blocks. In conclusion, the results suggested but not prove that Ca2+ and Mg2+ may have different mechanisms of action on peripheral nerves. While Ca2+ directly affects the gating of Na+ channels, action of Mg2+ can be explained by surface charge theory. PMID:12856822

Mert, Tufan; Gunes, Yasemin; Guven, Mustafa; Gunay, Ismail; Ozcengiz, Dilek

2003-01-01

5

A SIMPLE AND RAPID METHOD FOR THE SIMULTANEOUS DETERMINATION OF CALCIUM AND MAGNESIUM FROM THE SAME SAMPLE OF BLOOD SERUM  

PubMed Central

A simple and rapid procedure has been developed for the complexometric titration of serum calcium and magnesium using “plasmocorinth B” as indicator. Both determinations can be carried out from the same 0.5 ml. sample. The method is in good agreement with the established calcium and magnesium methods. PMID:14411396

Kovacs, G. S.; Tarnoky, K. E.

1960-01-01

6

A simple and rapid method for the simulataneous determination of calcium and magnesium from the same sample of blood serum.  

PubMed

A simple and rapid procedure has been developed for the complexometric titration of serum calcium and magnesium using "plasmocorinth B" as indicator. Both determinations can be carried out from the same 0.5 ml. sample. The method is in good agreement with the established calcium and magnesium methods. PMID:14411396

KOVACS, G S; TARNOKY, K E

1960-03-01

7

A SIMPLE AND RAPID METHOD FOR THE SIMULTANEOUS DETERMINATION OF CALCIUM AND MAGNESIUM FROM THE SAME SAMPLE OF BLOOD SERUM  

Microsoft Academic Search

A simple and rapid procedure has been developed for the complexometric titration of serum calcium and magnesium using “plasmocorinth B” as indicator. Both determinations can be carried out from the same 0.5 ml. sample. The method is in good agreement with the established calcium and magnesium methods.

G. S. Kovács; K. E. Tárnoky

1960-01-01

8

Regulation of Intracellular Calcium Concentrations by Calcium and Magnesium in Cardioplegic Solutions Protects Rat Neonatal Myocytes from Simulated Ischemia  

Microsoft Academic Search

The effects of calcium and magnesium ions in cardioplegic solutions on cardioprotection and intracellular calcium ion handling during ischemia and reoxygenation were investigated in cultured neonatal rat myocardial cells. Myocytes were subjected to simulated ischemia for 60 min at 37°C in hyperkalemic cardioplegic solutions containing various concentrations of calcium and magnesium ions, followed by 30 min of reoxygenation. For each

Takashi Ichiba; Naruto Matsuda; Naoaki Takemoto; Shingo Ishiguro; Hiroaki Kuroda; Tohru Mori

1998-01-01

9

Hair calcium and magnesium levels in patients with fibromyalgia: A case center study  

Microsoft Academic Search

Background: Fibromyalgia is not an uncom-mon condition. Because its cause has yet to be identified, treatment of the condition has been empirical; frequently, outcomes are unsatisfactory. Some patients with fibromyalgia were observed to have high hair calcium and magnesium levels compared with healthy subjects. Because of this and because supplementing calcium with magnesium to fibromyalgia subjects reduced the number of

Shu Yan Ng

1999-01-01

10

Extraction of phosphorus, potassium, calcium, and magnesium from soils by an ion?exchange resin procedure  

Microsoft Academic Search

A procedure for the simultaneous extraction of phosphorus, potassium, calcium and magnesium from soils, by an ion?exchange resin procedure applicable to large?scale advisory soil testing, is described. The important steps are the disaggregation of soil by shaking in water during 15 minutes with a glass marble, the transference of the elements from the soil to a sodium bicarbonate treated mixture

B. van Raij; J. A. Quaggio; N. M. da Silva

1986-01-01

11

Calcium and magnesium in drinking water and risk of death from acute myocardial infarction in Taiwan  

Microsoft Academic Search

Many studies have examined the association between cardiovascular disease mortality and water hardness. However, the results have not been consistent. This report examines whether calcium and magnesium in drinking water are protective against acute myocardial infarction (AMI). All eligible AMI deaths (10,094 cases) of Taiwan residents from 1994 to 2003 were compared with deaths from other causes (10,094 controls), and

Chun-Yuh Yang; Chih-Ching Chang; Shang-Shyue Tsai; Hui-Fen Chiu

2006-01-01

12

Influence of refined cellulose on human bowel function and calcium and magnesium balance13  

Microsoft Academic Search

The effect of cellulose purified from wood pulp on wet and dry stool weights, gastrointestinal transit time (TT), frequency of defecation, and calcium and magnesium balances was tested. Seven healthy women consumed a low fiber diet of constant composition (percentage of total kcal: 23% protein, 30% fat, 47% carbohydrate) and the same metabolically controlled diet to which 16 g of

J. L. Slavin; J. A. Marlett

13

Simultaneous determination of calcium and magnesium in water using artificial neural network spectro-photometric method  

NASA Astrophysics Data System (ADS)

A new analytical method using Back-Propagation (BP) artificial neural networks and spectrophotometry for simultaneous determination of calcium and magnesium in tap water, the Yellow River water and seawater is established. By condition experiment, the optimum analytical conditions for calcium, magnesium and Arsenazo (III) color reactions are obtained. Levenberg-Marquart (L-M) algorithm is used for calculation in BP neural network. The topological structure of three-layer BP ANN network architecture is chosen as 11-10-2 (nodes). The initial value of gradient coefficient ? is fixed at 0.001 and the increase factor and reduction factor of ? take the default values of the system. The data are processed by computers with our own programs written in MATLAB 7.0. The relative standard deviations of the calculated results for calcium and magnesium are 2.31% and 2.14%, respectively. The results of standard addition method show that the recoveries of calcium and magnesium are 103.6% and 100.8% in the tap water, 103.2% and 96.6% in the Yellow River water (Lijin district of Shandong Province), and 98.8%-103.3% and 98.43%-103.4% in seawater from Jiaozhou Bay of Qingdao. It is found that 14 common cations and anions do not interfere with the determination of calcium and magnesium under the optimum experimental conditions. The comparative experiments do not show any obvious difference between the results obtained by this new method and those obtained by the classical complexometric titration method in seawater medium. This method exhibits good reproducibility and high accuracy in the determination of calcium and magnesium and can be used for the simultaneous determination of Ca2+ and Mg2+ in tap water and natural water.

Ji, Hongwei; Li, Shuang; Xin, Huizhen; Cao, Hengxia

2010-09-01

14

Simultaneous determination of calcium and magnesium in water using artificial neural network spectro-photometric method  

Microsoft Academic Search

A new analytical method using Back-Propagation (BP) artificial neural networks and spectrophotometry for simultaneous determination\\u000a of calcium and magnesium in tap water, the Yellow River water and seawater is established. By condition experiment, the optimum\\u000a analytical conditions for calcium, magnesium and Arsenazo (III) color reactions are obtained. Levenberg-Marquart (L-M) algorithm\\u000a is used for calculation in BP neural network. The topological

Hongwei Ji; Shuang Li; Huizhen Xin; Hengxia Cao

2010-01-01

15

A rapid complexometric scheme for analysis of iron, aluminium, calcium and magnesium in slags.  

PubMed

A simple and rapid complexometric method has been developed for the simultaneous determination of iron, aluminium, calcium and magnesium in a single solution in slags. Phosphorous and small amounts of chromium (1.5 mg) and vanadium (1 mg) do not interfere in the titration. Titanium and manganese are suitably masked with lactic acid and tetra sodium pyrophosphate, respectively. In a suitable aliquot, iron is titrated at pH 2 with EDTA, using sulphosalicylic acid as indicator. To this solution, excess disodium 1,2-cyclohexane diamine tetra acetic acid (DCTA) is added and aluminium is titrated by titrating the excess DCTA with standard copper sulphate solution at pH 3.5, using 1-(2-pyridylazo)-2-naphthol (PAN) as an indicator. A known excess of EDTA is added, the pH is raised to 10 and calcium and magnesium are jointly titrated by titrating the excess EDTA with copper sulphate solution, using PAN indicator. The Ca-EDTA complex is demasked with ammonium oxalate at pH 5 and the released EDTA equivalent to calcium is titrated with copper sulphate solution at pH 10 with PAN indicator. Results of analysis compare favourably with certified values and values obtained by standard methods for BCS and other slags. A set of five samples can be analysed for iron, aluminium, calcium and magnesium in four hours as compared to three days by the classical conventional method. PMID:18965436

Ghosh, K C; Mukherjee, B C; Ganguly, N N; Yusuf, M; Choudhury, V N

1992-06-01

16

Improved methods for reducing calcium and magnesium concentrations in tissue culture medium: Application to studies of lymphoblast proliferation in vitro  

Microsoft Academic Search

Summary  We have compared several methods for reducing calcium and magnesium concentrations in tissue culture medium, with the objective\\u000a of producing selective deficiency effects on the growth of mouse (L5178Y) and human (P1R) lymphoblasts. In experiments in\\u000a which calcium- and magnesium-“free” McCoy’s medium was supplemented with 15% horse or fetal calf serum, enough calcium and\\u000a magnesium was provided by serum to

James K. Brennan; James Mansky; Geraldine Roberts; Marshall A. Lichtman

1975-01-01

17

Thyroxine-induced stimulation of hepatic cell transport of calcium and magnesium  

PubMed Central

The effect of L-thyroxine on the bidirectional transport of calcium and magnesium in rat liver was assessed in vitro. An increase of 34% in the fractional coefficient for calcium influx was observed 24 hr after the administration of 500 ?g of thyroxine. Chronic treatment with thyroxine for 1 and 3 wk at a dose of 750 ?g/wk resulted in increases in calcium influx of 57 and 51%, respectively. Calcium efflux was increased irregularly, by 14-26%. Magnesium transport measured in a similar system was not altered by 24 or 48 hr of treatment with thyroxine, but continuation of treatment for 1-3 wk resulted in increases in magnesium influx of 47-49%. Magnesium efflux was not significantly affected. Neither increased cellular binding of divalent cations nor enhanced protein synthesis could be incriminated in the stimulatory effect of thyroxine on divalent cation transport. Actinomycin-D and D,L-ethionine, inhibitors of protein synthesis, stimulated calcium and magnesium transport in liver independently of the effects of thyroxine. These data present the possibility that certain actions of thyroid hormone may be mediated or modulated by associated, direct changes in the cellular transport and intracellular concentrations of divalent cations. PMID:4260122

Wallach, Stanley; Bellavia, J. V.; Gamponia, P. J.; Bristrim, P.

1972-01-01

18

Effects of dietary vitamin D on calcium and magnesium levels in mice with abnormal calcium metabolism  

SciTech Connect

In previous studies vitamin D has been used to induce cardiac calcium overload in laboratory animals. Interrelationships between calcium and magnesium metabolism are also documented. The authors have investigated the effect of varying vitamin D in the diet on calcium and magnesium levels in plasma, kidney and heart of DBA mice which exhibit genetic abnormalities in cardiac calcium metabolism. Weanling DBA mice were maintained for 28 days on an AIN-76 diet containing either 1,000 I.U. of vitamin D{sub 3} per kg of diet (control); 4,000 I.U. of vitamin D{sub 3} per kg of diet; or no vitamin D. When compared to controls, supplemented animals showed significantly higher plasma magnesium, kidney calcium and kidney magnesium levels; animals receiving the vitamin D-deficient diet exhibited increases in cardiac calcium levels. The authors results support previous findings that vitamin D deficiency increases cardiac calcium uptake and suggest a possible role of vitamin D in magnesium metabolism.

Spurlock, B.G.; West, W.L.; Knight, E.M. (Howard Univ., Washington, DC (United States))

1991-03-11

19

Calcium and Magnesium Levels in Agricultural Soil and Sewage Sludge in an Industrial Area from Southeastern Spain: Relationship with Plant (Saccharum officinarum) Disposition  

Microsoft Academic Search

This investigation was initiated to assess the following objectives: (1) to measure the total calcium and magnesium content in agricultural soil and sewage sludge from the Mediterranean coastal area of Motril (southeastern Spain); (2) to determine the pH values of indicated samples in order to evaluate first their influence on calcium and magnesium content, and second on levels of these

A. M. Jodral-Segado; M. Navarro-Alarcón; H. López-G De La Serrana; M. C. López-Martínez

2006-01-01

20

[Simultaneous determination of calcium and magnesium by calculative spectrophotometric complexometric titration].  

PubMed

A new spectrophotometric complexometric titration method coupled with chemometrics for the determination of mixtures of metal ions has been developed. In the method described here, the titrant is a mixture of EDTA and two indicators. In the process of titration, both the volumetric addition of titrant and the progress of titration reaction can be characterized simultaneously by chemometric calculation with the absorption spectra, and then the titration curves can be obtained. With the titration curves, a matrix equation can be established, and thus the concentration of each component in the mixture of metal ions can be calculated with principal component regression. The method only needs the information of absorption spectra to obtain the analytical results, and is free of volumetric measurements. So the method is simple, convenient and precise, and has been applied to the simultaneous determination of mixtures of calcium and magnesium using malachite green and Cu-PAN as indicators with satisfactory results. PMID:18330321

Liao, Li-fu; Xiao, Xi-lin; Yang, Ming-hui; Yang, Jing

2007-12-01

21

Continental weathering following a Cryogenian glaciation: Evidence from calcium and magnesium isotopes  

NASA Astrophysics Data System (ADS)

A marked ocean acidification event and elevated atmospheric carbon dioxide concentrations following the extreme environmental conditions of the younger Cryogenian glaciation have been inferred from boron isotope measurements. Calcium and magnesium isotope analyses offer additional insights into the processes occurring during this time. Data from Neoproterozoic sections in Namibia indicate that following the end of glaciation the continental weathering flux transitioned from being of mixed carbonate and silicate character to a silicate-dominated one. Combined with the effects of primary dolomite formation in the cap dolostones, this caused the ocean to depart from a state of acidification and return to higher pH after climatic amelioration. Differences in the magnitude of stratigraphic isotopic changes across the continental margin of the southern Congo craton shelf point to local influences modifying and amplifying the global signal, which need to be considered in order to avoid overestimation of the worldwide chemical weathering flux.

Kasemann, Simone A.; Pogge von Strandmann, Philip A. E.; Prave, Anthony R.; Fallick, Anthony E.; Elliott, Tim; Hoffmann, Karl-Heinz

2014-06-01

22

Revised model of calcium and magnesium binding to the bacterial cell wall.  

PubMed

Metals bind to the bacterial cell wall, yet the binding mechanisms and affinity constants are not fully understood. The cell wall of gram positive bacteria is characterized by a thick layer of peptidoglycan and anionic teichoic acids anchored in the cytoplasmic membrane as lipoteichoic acid or covalently bound to the cell wall as wall teichoic acid. The polyphosphate groups of teichoic acid provide one-half of the metal binding sites for calcium and magnesium, which contradicts previous reports that calcium binding is 100 % dependent on teichoic acid. The remaining binding sites are formed with the carboxyl units of peptidoglycan. In this work we report equilibrium association constants and total metal binding capacities for the interaction of calcium and magnesium ions with the bacterial cell wall. Metal binding is much stronger than previously reported. Curvature of Scatchard plots from the binding data and the resulting two regions of binding affinity suggest the presence of negative cooperative binding, which means that the binding affinity decreases as more ions become bound to the sample. For Ca(2+), Region I has a KA = (1.0 ± 0.2) × 10(6) M(-1) and Region II has a KA = (0.075 ± 0.058) × 10(6) M(-1). For Mg(2+), KA1 = (1.5 ± 0.1) × 10(6) and KA2 = (0.17 ± 0.10) × 10(6). A binding capacity (?) is reported for both regions. However, since binding is still occurring in Region II, the total binding capacity is denoted by ?2, which are 0.70 ± 0.04 and 0.67 ± 0.03 µmol/mg for Ca(2+) and Mg(2+) respectively. These data contradict the current paradigm of only a single metal affinity value that is constant over a range of concentrations. We also find that measurement of equilibrium binding constants is highly sample dependent. This suggests a role for diffusion of metals through heterogeneous cell wall fragments. As a result, we are able to reconcile many contradictory theories that describe binding affinity and the binding mode of divalent metal cations. PMID:25315444

Thomas, Kieth J; Rice, Charles V

2014-12-01

23

Calcium and magnesium interference studies for the binding of heavy metal ions in solution by Medicago sativa (alfalfa)  

SciTech Connect

Previous batch laboratory experiments performed to determine the potential ability of seven different varieties of Medicago sativa (alfalfa) revealed that the African shoots population was able to efficiently bind copper(II) and nickel(II) from aqueous solutions. Batch laboratory interference studies were performed with various calcium and magnesium concentrations (0.1 mM to 1 M) in order to ascertain the effects of these ions on the heavy metal binding ability of African alfalfa shoots. Results from these studies have shown that calcium and magnesium did not seriously reduce the binding of copper(II) and lead(II) to African alfalfa shoots. However, high concentrations of calcium and magnesium significantly reduced chromium(III), cadmium(II), nickel(II), and zinc(II) binding to African shoots. In addition, all these experiments were repeated maintaining the ionic strength constant, and similar results were obtained. Interference studies were also conducted in order to determine the effects of hard cations under flow conditions with silica-immobilized African alfalfa shoots. The information obtained from these studies will be useful for an innovative method of heavy metal ion removal and recovery from contaminated waters.

Gardea-Torresdey, J.L.; Tiemann, K.J.; Gonzalez, J.H. [Univ. of Texas, El Paso, TX (United States). Dept. of Chemistry; Henning, J.A.; Townsend, M.S. [New Mexico State Univ., Las Cruces, NM (United States). Dept. of Agronomy and Horticulture

1996-12-31

24

Calcium and Magnesium Levels in Agricultural Soil and Sewage Sludge in an Industrial Area from Southeastern Spain: Relationship with Plant (Saccharum officinarum) Disposition  

E-print Network

This investigation was initiated to assess the following objectives: (1) to measure the total calcium and magnesium content in agricultural soil and sewage sludge from the Mediterranean coastal area of Motril (southeastern Spain); (2) to determine the pH values of indicated samples in order to evaluate first their influence on calcium and magnesium content, and second on levels of these minerals in the main crop (sugar cane: Saccharum officinarum)grown in the area; (3) to study the influence of industrial activities, first on calcium and magnesium cantents and pH values in agricultural soil, and second on calcium and magnesium concentrations present in sugar cane samples; (4) to check if the calcium and magnesium levels existing in agricultural soil exert any influence on corresponding element uptake by sugar cane plants. Calcium levels found in agricultural soil were significantly higher (p magnesium concentrations in agricultural soil and sewage sludge (p magnesium levels in the sugar cane plants. Calcium and magnesium concentrations existing in agricultural soil did not significantly influence the element uptake by sugar cane plants.

A. M. Jodral-segado; M. Navarro-alarcón; H. López-g; De La Serrana; M. C. López-martínez

25

Dissolved Calcium and Magnesium Carbonates Promote Arsenate Release From Ferrihydrite in Flow Systems  

NASA Astrophysics Data System (ADS)

Field data from water systems around the world have shown that arsenic can reach toxic concentrations in dynamic groundwater systems. This is generally in contrast to analogous static systems at circumneutral pH, where arsenic is strongly retained by sorption to iron (hydr)oxides. Our research examines the effect of calcium and magnesium carbonates on As(V) mobility. In both dynamic flow and static experiments, arsenate was pre- sorbed to poorly crystalline iron hydroxides (1-10% sorption capacity), with varying aqueous compositions including calcium, magnesium, carbonate, sulfate, lactate, and other common groundwater species (pH 7.5-8). Thus we investigated how the dissolution of common carbonate minerals, specifically CaCO3 and MgCO3, affect arsenic behavior in the context of groundwater solutions. Under static (batch) conditions, no measurable arsenic (<10 ?g/L) is released into solutions containing alkaline earth metals (AEMs) and carbonates. When elevated concentrations of AEMs and carbonate are introduced by dynamic flow, however, arsenic is mobilized at up to 500 ?g/L, releasing significant proportions the total arsenic present. This is only the case when both of these species are present; with other common ion pairs, little to no arsenic is released. These results indicate that arsenate adsorption is kinetically controlled under flow conditions, resulting in very different mobility relative to otherwise equivalent static systems. Furthermore, the combination of alkaline earth metals and carbonates promotes As(V) mobility in column-based systems. We propose that these phenomena indicate a combination of physical and chemical effects by which diffusion limitation becomes dominant in limiting arsenic sorption in flow systems. Many carbonate-buffered aquifers, as well as those undergoing rapid mineralization of organic matter, could be affected by these processes of AEM-carbonate-limited sorption and increased arsenic mobility.

Saalfield, S. L.; Bostick, B. C.

2007-12-01

26

Calcium and magnesium in exocrine secretion--an X-ray microanalytical study  

SciTech Connect

Calcium and magnesium distribution in mammalian exocrine glands under resting, stimulated and pathological conditions was investigated by X-ray microanalysis of thick and ultrathin cryosections. Ultrathin sections were cut from tissue frozen in the presence of a polymer cryoprotectant, dextran. The effect of this treatment on isolated rabbit pancreas. Dextran caused a disturbance in water and ion transport, partly due to an osmotic effect and the impermeability of the pancreatic epithelium to dextran; this does, however, not necessarily invalidate intracellular measurements on frozen-dried sections. Cholinergic stimulation of the rat pancreas caused a change of Ca distribution from the basal to the apical part of the cell; this may be a component of the secretory Ca flux. Kinetic considerations make a significant Ca movement via the ER-Golgi endomembrane space less likely. The mitochondrial Ca concentration is low, and not significantly changed by cholinergic stimulation. X-ray microanalysis was carried out on submandibular glands of rats after chronic treatment with reserpin and/or isoproterenol (an animal model for cystic fibrosis, CF). The acinar cells had elevated Mg and Ca and lowered K concentrations. Analysis of ultrathin cryosections showed high levels of Ca and Mg in secretory granules, mucus globules and the ER. Ca and Mg in the ER may be transported intracellularly with secretory proteins to secretion granules or mucus globules. The decrease in cell K may be due to efflux of K caused by elevated cytoplasmic Ca levels. A similar decrease in cell K was caused by incubation of rat salivary glands with diluted serum from CF patients, a treatment which has been reported to mimic the effect of a rise in cytoplasmic Ca.

Roomans, G.M.; Barnard, T.

1982-01-01

27

Chelatometric determination of calcium and magnesium in iron ores, slags, anorthosite, limestone, copper-nickel-lead-zinc ores and divers materials.  

PubMed

Chelatometric methods for the determination of calcium and magnesium in iron ores, slags, anorthosite, copper-nickel-lead-zinc ores and various other materials are described. Potential interfering elements are masked with triethanolamine and potassium cyanide. In one aliquot calcium is titrated at pH > 12, with calcein and thymolphthalein mixed indicator and in another aliquot calcium and magnesium are titrated in ammonia buffer, with o-cresolphthalein complexone screened with Naphthol Green B as indicator. The results compare favourably with certified values for reference materials of diverse nature. PMID:18962661

Hitchen, A; Zechanowitsch, G

1980-03-01

28

Comparison of calcium and magnesium contents in cruciferous vegetables grown in areas around steelworks, on organic farms, and those available in retail.  

PubMed

The aim of the present study was to compare calcium and magnesium contents in cruciferous vegetables grown under diversified ecological conditions for three consecutive years, independently of the climatic and agrotechnical conditions. The metal contents were determined using validated Atomic Absorption Spectrometry with atomization in the flame (FAAS method; spectrometer: AA240FS Varian). The dry mass of various vegetable species cultivated on organic farms contained, in most cases, significantly higher or similar calcium and magnesium amounts in comparison with those from farms located in the closest vicinity of steelworks and those purchased at local markets. Cruciferous vegetables from the two latter sources showed comparable contents of the essential minerals under study. PMID:21888594

Kapusta-Duch, Joanna; Leszczy?ska, Teresa; Florkiewicz, Adam; Filipiak-Florkiewicz, Agnieszka

2011-01-01

29

Effects of calcium and magnesium on acute and chronic neurotoxicity caused by oxaliplatin: A meta-analysis  

PubMed Central

The primary toxicity of oxaliplatin is neurotoxicity. Calcium and magnesium (Ca/Mg) are reported to be beneficial in protecting against this adverse effect. However, the results obtained from clinical trials are not definitive. The aim of this study was to evaluate whether Ca/Mg alleviates the neurotoxicity of oxaliplatin by performing a meta-analysis of the literature involving available randomized controlled trials. Systematic searches for trials were undertaken from the Cochrane Library, MEDLINE, CENTRAL, Embase, CBMdisc and CNKI databases without language limitations. The primary outcome was severe chronic neurotoxicity and the secondary outcome was acute neurotoxicity. Four randomized double-blind trials met the search criteria. The odds ratio (OR) comparing Ca/Mg treatment with placebo was 0.44 (0.23–0.85, P=0.01) for severe chronic neurotoxicity of oxaliplatin (grade ?2) and 0.41 (0.11–1.49, P=0.18) for acute neurotoxicity. In conclusion, Ca/Mg treatment does not reduce the incidence of acute neurotoxicity of oxaliplatin, but does reduce the incidence of severe chronic neurotoxicity (grade ?2). No differences were observed in the outcomes of chemotherapy. Thus, Ca/Mg treatment is recommended for use as an adjunct with oxaliplatin. PMID:23226752

AO, RUI; WANG, YU-HUI; LI, RUI-WEN; WANG, ZHENG-RONG

2012-01-01

30

Effect of Metal Chelators on ?-Secretase Indicates That Calcium and Magnesium Ions Facilitate Cleavage of Alzheimer Amyloid Precursor Substrate  

PubMed Central

Gamma-secretase is involved in the production of A? amyloid peptides. It cleaves the transmembrane domain of the amyloid precursor protein (APP) at alternative sites to produce A? and the APP intracellular domain (AICD). Metal ions play an important role in A? aggregation and metabolism, thus metal chelators and ligands represent potential therapeutic agents for AD treatment. A direct effect of metal chelators on ?-secretase has not yet been investigated. The authors used an in vitro? ?-secretase assay consisting of cleavage of APP C100-3XFLAG by endogenous ?-secretase from rodent brains and human neuroblastoma SH-SY5Y, and detected AICD production by western blotting. Adding metalloprotease inhibitors to the reaction showed that clioquinol, phosphoramidon, and zinc metalloprotease inhibitors had no significant effect on ?-secretase activity. In contrast, phenanthroline, EDTA, and EGTA markedly decreased ?-secretase activity that could be restored by adding back calcium and magnesium ions. Mg2+ stabilized a 1,000?kDa presenilin 1 complex through blue native gel electrophoresis and size-exclusion chromatography. Data suggest that Ca2+ and Mg2+ stabilize ?-secretase and enhance its activity. PMID:21253550

Ho, Michael; Hoke, David E.; Chua, Yee Jia; Li, Qiao-Xin; Culvenor, Janetta G.; Masters, Colin; White, Anthony R.; Evin, Genevieve

2011-01-01

31

The role of calcium and magnesium ions in uptake of beta-amyloid peptides by microglial cells.  

PubMed

Amyloid peptides 1-40 and 1-42 (Abeta 1-40 and Abeta 1-42) are major components of diffuse and neuritic senile plaques present in the brain of patients with Alzheimers disease. Their interaction with microglial cells was studied using a system partly mimicking these plaques, which consisted in heat-killed yeast particles coated with either Abeta 1-40 or Abeta 1-42. Using these particles, it has been shown in our laboratory that LRP is involved mainly in the elimination of Abeta 1-42-coated heat-killed yeast particles and partly in that of Abeta 1-40-coated heat-killed yeast particles by microglial cells in culture. We show here that in the presence of calcium and magnesium ions extracellular chelators, namely EDTA (for both ions) and EGTA (for calcium ions), the internalization of coated heat-killed particles was impaired. In the presence of BAPTA-AM, an intracellular chelator of calcium ions and thapsigargin, an inhibitor of the endoplasmic reticulum calcium pump, no effect was observed on the phagocytosis of Abeta 1-40-coated heat-killed yeast particles, whereas that of Abeta 1-42-coated heat-killed yeast particles was affected. These results suggest that different signaling mechanisms are involved after the internalization of Abeta 1-40 and Abeta 1-42. PMID:17026853

Choucair, N; Laporte, V; Levy, R; Tranchant, C; Gies, J-P; Poindron, P; Lombard, Y

2006-01-01

32

Short term spatio-temporal variability of soil water-extractable calcium and magnesium after a low severity grassland fire in Lithuania.  

NASA Astrophysics Data System (ADS)

Fire has important impacts on soil nutrient spatio-temporal distribution (Outeiro et al., 2008). This impact depends on fire severity, topography of the burned area, type of soil and vegetation affected, and the meteorological conditions post-fire. Fire produces a complex mosaic of impacts in soil that can be extremely variable at small plot scale in the space and time. In order to assess and map such a heterogeneous distribution, the test of interpolation methods is fundamental to identify the best estimator and to have a better understanding of soil nutrients spatial distribution. The objective of this work is to identify the short-term spatial variability of water-extractable calcium and magnesium after a low severity grassland fire. The studied area is located near Vilnius (Lithuania) at 54° 42' N, 25° 08 E, 158 masl. Four days after the fire, it was designed in a burned area a plot with 400 m2 (20 x 20 m with 5 m space between sampling points). Twenty five samples from top soil (0-5 cm) were collected immediately after the fire (IAF), 2, 5, 7 and 9 months after the fire (a total of 125 in all sampling dates). The original data of water-extractable calcium and magnesium did not respected the Gaussian distribution, thus a neperian logarithm (ln) was applied in order to normalize data. Significant differences of water-extractable calcium and magnesium among sampling dates were carried out with the Anova One-way test using the ln data. In order to assess the spatial variability of water-extractable calcium and magnesium, we tested several interpolation methods as Ordinary Kriging (OK), Inverse Distance to a Weight (IDW) with the power of 1, 2, 3 and 4, Radial Basis Functions (RBF) - Inverse Multiquadratic (IMT), Multilog (MTG), Multiquadratic (MTQ) Natural Cubic Spline (NCS) and Thin Plate Spline (TPS) - and Local Polynomial (LP) with the power of 1 and 2. Interpolation tests were carried out with Ln data. The best interpolation method was assessed using the cross validation method. Cross-validation was obtained by taking each observation in turn out of the sample pool and estimating from the remaining ones. The errors produced (observed-predicted) are used to evaluate the performance of each method. With these data, the mean error (ME) and root mean square error (RMSE) were calculated. The best method was the one which had the lower RMSE (Pereira et al. in press). The results shown significant differences among sampling dates in the water-extractable calcium (F= 138.78, p< 0.001) and extractable magnesium (F= 160.66; p< 0.001). Water-extractable calcium and magnesium was high IAF decreasing until 7 months after the fire, rising in the last sampling date. Among the tested methods, the most accurate to interpolate the water-extractable calcium were: IAF-IDW1; 2 Months-IDW1; 5 months-OK; 7 Months-IDW4 and 9 Months-IDW3. In relation to water-extractable magnesium the best interpolation techniques were: IAF-IDW2; 2 Months-IDW1; 5 months- IDW3; 7 Months-TPS and 9 Months-IDW1. These results suggested that the spatial variability of these water-extractable is variable with the time. The causes of this variability will be discussed during the presentation. References Outeiro, L., Aspero, F., Ubeda, X. (2008) Geostatistical methods to study spatial variability of soil cation after a prescribed fire and rainfall. Catena, 74: 310-320. Pereira, P., Cerdà, A., Úbeda, X., Mataix-Solera, J. Arcenegui, V., Zavala, L. Modelling the impacts of wildfire on ash thickness in a short-term period, Land Degradation and Development, (In Press), DOI: 10.1002/ldr.2195

Pereira, Paulo; Martin, David

2014-05-01

33

Phase I drug-interaction study of effects of calcium and magnesium infusions on oxaliplatin pharmacokinetics and acute neurotoxicity in colorectal cancer patients  

PubMed Central

Background Calcium and magnesium (Ca/Mg) infusions have been suggested as an effective intervention for preventing oxaliplatin-induced neurotoxicity, but the effects of Ca/Mg infusions on oxaliplatin pharmacokinetics, motor nerve hyperexcitability and acute neurotoxicity symptoms are unclear. Methods In this double blind crossover study, colorectal cancer patients undergoing oxaliplatin-based chemotherapy were randomised to receive Ca/Mg (1g Ca Gluconate plus 1g MgSO4) on cycle 1 and placebo (vehicle alone) on cycle 2, or to receive the same treatments in the opposite sequence. Study endpoints included plasma pharmacokinetics of intact oxaliplatin and free platinum; electromyography (EMG) detection of abnormal spontaneous high-frequency motor unit action potential discharges; and patient-reported acute neurotoxicity symptoms and their preferred study treatment for reducing these symptoms. Results Nineteen of 20 enrolled patients completed the study. Plasma pharmacokinetics of intact oxaliplatin and free platinum were similar when oxaliplatin was given with Ca/Mg or placebo (ratio of geometric means of AUC0-t with Ca/Mg or placebo: intact oxaliplatin, 0.95 (90% CI, 0.90 – 1.01); free platinum, 0.99 (90% CI, 0.94 – 1.05)). EMG motor nerve hyperexcitability scores were similar with Ca/Mg and placebo (mean difference in EMG score between Ca/Mg and placebo: -0.3 (95% CI, -2.2 – 1.6)). Patient-reported acute neurotoxicity symptoms were similar in frequency with Ca/Mg and placebo. For reducing neurotoxic symptoms, fewer patients preferred Ca/Mg than placebo or neither treatment (26% versus 74%; P<0.01). Conclusions Ca/Mg infusions do not alter the clinical pharmacokinetics of oxaliplatin and do not seem to reduce its acute neurotoxicity. Trial registration Trial registration identifier ACTRN12611000738921 PMID:24156389

2013-01-01

34

Kinetic characterization and gene expression of adenosine deaminase in intact trophozoites of Trichomonas vaginalis.  

PubMed

Trichomonas vaginalis is a parasite that resides in the human urogenital tract and causes trichomonosis, the most prevalent nonviral sexually transmitted disease. Nucleoside triphosphate diphosphohydrolase (NTPDase), which hydrolyzes extracellular di- and triphosphate nucleotides, and ecto-5'-nucleotidase, which hydrolyzes AMP, have been characterized in T. vaginalis. The aim of this study was to characterize the adenosine deaminase (ADA) activity in intact trophozoites of T. vaginalis. A strong inhibition in adenosine deamination was observed in the presence of calcium and magnesium, which was prevented by EDTA. The apparent K(M) value for adenosine was 1.13 ± 0.07mM. The calculated V(max) was 2.61 ± 0.054 nmol NH(3) min(-1) mg(-1) protein. Adenosine deamination was inhibited in the presence of erythro-9-(2-hydroxy-3-nonyl)adenine. Semi-quantitative reverse transcriptase-PCR experiments were performed and both ADA-related genes ada(125) and ada(231) mRNA were expressed, although ada(231) in higher quantity when compared with the ada(125) : ?-tubulin ratio. Furthermore, a phylogenetic analysis showed that the T. vaginalis sequences formed a clade with Entamoeba histolytica and Dictyostelium discoideum sequences, and it strongly suggests homologous functions in the T. vaginalis genome. The presence of ADA activity in T. vaginalis may be important to modulate the adenosine/inosine levels during infection and, consequently, to maintain the anti-inflammatory properties through different nucleoside-signalling mechanisms. PMID:21477257

Weizenmann, Marina; Frasson, Amanda Piccoli; de Barros, Muriel Primon; Vieira, Patrícia de Brum; Rosemberg, Denis Broock; De Carli, Geraldo Attilio; Bogo, Maurício Reis; Bonan, Carla Denise; Tasca, Tiana

2011-06-01

35

Adenosine and blood platelets  

Microsoft Academic Search

Adenosine is an important regulatory metabolite and an inhibitor of platelet activation. Adenosine released from different\\u000a cells or generated through the activity of cell-surface ectoenzymes exerts its effects through the binding of four different\\u000a G-protein-coupled adenosine receptors. In platelets, binding of A2 subtypes (A2A or A2B) leads to consequent elevation of intracellular cyclic adenosine monophosphate, an inhibitor of platelet activation.

Hillary A. Johnston-Cox; Katya Ravid

36

Adenosine dysfunction in epilepsy  

PubMed Central

Extracellular levels of the brain’s endogenous anticonvulsant and neuroprotectant adenosine largely depend on an astrocyte-based adenosine cycle, comprised of ATP release, rapid degradation of ATP into adenosine, and metabolic reuptake of adenosine through equilibrative nucleoside transporters and phosphorylation by adenosine kinase (ADK). Changes in ADK expression and activity therefore rapidly translate into changes of extracellular adenosine, which exerts its potent anticonvulsive and neuroprotective effects by activation of pre- and postsynaptic adenosine A1 receptors. Increases in ADK increase neuronal excitability, whereas decreases in ADK render the brain resistant to seizures and injury. Importantly, ADK was found to be overexpressed and associated with astrogliosis and spontaneous seizures in rodent models of epilepsy, as well as in human specimen resected from patients with hippocampal sclerosis and temporal lobe epilepsy. Several lines of evidence indicate that overexpression of astroglial ADK and adenosine deficiency are pathological hallmarks of the epileptic brain. Consequently, adenosine augmentation therapies constitute a powerful approach for seizure prevention, which is effective in models of epilepsy that are resistant to conventional antiepileptic drugs. The adenosine kinase hypothesis of epileptogenesis suggests that adenosine dysfunction in epilepsy undergoes a biphasic response: An acute surge of adenosine that can be triggered by any type of injury might contribute to the development of astrogliosis via adenosine receptor –dependent and –independent mechanisms. Astrogliosis in turn is associated with overexpression of ADK, which was shown to be sufficient to trigger spontaneous recurrent electrographic seizures. Thus, ADK emerges as a promising target for the prediction and prevention of epilepsy. PMID:22700220

Boison, Detlev

2011-01-01

37

Adenosine and ATP Receptors  

Microsoft Academic Search

Adenosine and ATP, via P1 and P2 receptors respectively, can modulate pain transmission under physiological, inflammatory,\\u000a and neuropathic pain conditions. Such influences reflect peripheral and central actions and effects on neurons as well as\\u000a other cell types. In general, adenosine A1 receptors produce inhibitory effects on pain in a number of preclinical models\\u000a and are a focus of attention. In

J. Sawynok

38

Adenosine and Bone Metabolism  

PubMed Central

Bone is a dynamic organ that undergoes continuous remodeling whilst maintaining a balance between bone formation and resorption. Osteoblasts, which synthesize and mineralize new bone, and osteoclasts, the cells that resorb bone, act in concert to maintain bone homeostasis. In recent years, there has been increasing appreciation of purinergic regulation of bone metabolism. Adenosine, released locally, mediates its physiologic and pharmacologic actions via interactions with G-protein coupled receptors and recent work has indicated that these receptors are involved in the regulation of osteoclast differentiation and function, as well as osteoblast differentiation and bone formation. Moreover, adenosine receptors also regulate chondrocyte and cartilage homeostasis. These recent findings underscore the potential therapeutic importance of adenosine receptors in regulating bone physiology and pathology. PMID:23499155

Mediero, Aranzazu; Cronstein, Bruce N.

2013-01-01

39

Caffeine and adenosine.  

PubMed

Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine. PMID:20164566

Ribeiro, Joaquim A; Sebastião, Ana M

2010-01-01

40

Rat cardiac myocyte adenosine transport and metabolism  

SciTech Connect

Based on the importance of myocardial adenosine and adenine nucleotide metabolism, the adenosine salvage pathway in ventricular myocytes was studied. Accurate estimates of transport rates, separate from metabolic fllux, were determined. Adenosine influx was constant between 3 and 60 s. Adenosine metabolism maintained intracellular adenosine concentrations < 10% of the extracellular adenosine concentrations and thus unidirectional influx could be measured. Myocytes transported adenosine via saturable and nonsaturable processes. A minimum estimate of the V/sub max/ of myocytic adenosine kinase indicated the saturable component of adenosine influx was independent of adenosine kinase activity. Saturable transport was inhibited by nitrobenzylthioinosine and verapamil. Extracellular adenosine taken up myocytes was rapidly phosphorylated to adenine taken up by myocytes was rapidly phosphorylated to adenine nucleotides. Not all extracellular adenosine, though, was phosphorylated on entering myocytes, since free, as opposed to protein-bound, intracellular adenosine was detected after digitonin extraction of cells in the presence of 1 mM ethylene-diaminetetraacetic acid.

Ford, D.A.; Rovetto, M.J.

1987-01-01

41

Regulation of adenosine receptor engagement by ecto-adenosine deaminase  

Microsoft Academic Search

Adenosine deaminase (ADA) can localize to the cell surface through its interaction with CD26. Using CD26-transfected cells, we demonstrate that cell surface ADA (ecto-ADA) can regulate adenosine receptor engagement by degrading extracellular adenosine (Ado) to inosine. This ability was dependent upon CD26 expression, the extent of CD26 saturation with ecto-ADA, and the kinetics of the cAMP response. Thus, the cAMP

Tomoko Hashikawa; Scott W. Hooker; Jerzy G. Maj; Christopher J. Knott-Craig; Masahide Takedachi; Shinya Murakami; Linda F. Thompson

2003-01-01

42

Adenosine and Gastrointestinal Inflammation  

PubMed Central

Nucelosides such as adenosine (Ado) influence nearly every aspect of physiology and pathophysiology. Extracellular nucleotides liberated at local sites of inflammation are metabolized through regulated phosphohydrolysis by a series of ecto-nucleotidases including ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5?-nucleotidase (CD73), found on the surface of a variety of cell types. Once generated, Ado is made available to bind and activate one of four G-protein-coupled Ado receptors. Recent in vitro and in vivo studies implicate Ado in a broad array of tissue protective mechanisms that provide new insight into adenosine actions. Studies in cultured cells and murine tissues have indicated that Ado receptors couple to novel post-translational protein modifications, including Cullin deneddylation, as a new anti-inflammatory mechanism. Studies in Ado receptor-null mice have been revealing and indicate a particularly important role for the Ado A2B receptor in animal models of intestinal inflammation. Here, we review contributions of Ado to cell and tissue stress responses, with a particular emphasis on the gastrointestinal mucosa. PMID:23296303

Colgan, Sean P.; Fennimore, Blair; Ehrentraut, Stefan F.

2013-01-01

43

Urinary excretion of calcium and magnesium in children  

Microsoft Academic Search

Urine calcium excretion in healthy children was 2·38±0·66 (SD; no. = 52) mg\\/kg per 24 hr and urinary magnesium excretion was 2·82±0·79 (SD; no. = 23). The 24-hour urine calcium excretion could be predicted with reasonable confidence from the calcium\\/creatinine concentration ratio of the second urine specimen passed in the morning. In this specimen the urine calcium\\/creatinine concentration ratio was

S. Ghazali; T. M. Barratt

1974-01-01

44

Spectrophotometric Titration of a Mixture of Calcium and Magnesium.  

ERIC Educational Resources Information Center

Describes a spectrophotometric titration experiment which uses a manual titration spectrophotometer and manually operated buret, rather than special instrumentation. Identifies the equipment, materials, and procedures needed for the completion of the experiment. Recommends the use of this experiment in introductory quantitative analysis…

Fulton, Robert; And Others

1986-01-01

45

Urinary excretion of calcium and magnesium in children  

PubMed Central

Urine calcium excretion in healthy children was 2·38±0·66 (SD; no. = 52) mg/kg per 24 hr and urinary magnesium excretion was 2·82±0·79 (SD; no. = 23). The 24-hour urine calcium excretion could be predicted with reasonable confidence from the calcium/creatinine concentration ratio of the second urine specimen passed in the morning. In this specimen the urine calcium/creatinine concentration ratio was 0·14±0·06 (SD; no. = 60) mg/mg and the magnesium/creatinine concentration ratio was 0·21±0·10 (SD; no. = 29) mg/mg. The upper limit of the urine calcium excretion is taken to be 4 mg/kg per 24 hr and that of the calcium/creatinine concentration ratio in the second morning urine is 0·25 mg/mg. After a milk load of 700 ml/1·73 m2 the urinary calcium/creatinine concentration ratio rose in the first two hours, but in no sample exceeded 0·25 mg/mg. PMID:4406087

Ghazali, S.; Barratt, T. M.

1974-01-01

46

Molecular mechanisms of calcium and magnesium binding to parvalbumin.  

PubMed Central

Molecular dynamics simulations have been used to investigate the relationship between the coordinating residues of the EF-hand calcium binding loop of parvalbumin and the overall plasticity and flexibility of the protein. The first simulation modeled the transition from Ca(2+) to Mg(2+) coordination by varying the van der Waals parameters for the bound metal ions. The glutamate at position 12 could be accurately and reversibly seen to be a source of selective bidentate ligation of Ca(2+) in the simulations. A second simulation correlated well with the experimental observation that an E101D substitution at EF loop position 12 results in a dramatically less tightly bound monodentate Ca(2+) coordination by aspartate. A final set of simulations investigated Ca(2+) binding in the E101D mutant loop in the presence of applied external forces designed to impose bidentate coordination. The results of these simulations illustrate that the aspartate is capable of attaining a suitable orientation for bidentate coordination, thus implying that it is the inherent rigidity of the loop that prevents bidentate coordination in the parvalbumin E101D mutant. PMID:11867433

Cates, M Susan; Teodoro, Miguel L; Phillips, George N

2002-01-01

47

Adenosine and adenosine analogs inhibit phosphodiesterase activity in the heart  

Microsoft Academic Search

Adenosine and its analogs (-)-N6-phenylisopropyladenosine and 5'-N-ethylcarboxamideadenosine inhibit cAMP and cGMP phosphodiesterase activity in guinea-pig atrial and ventricular preparations at concentrations of 100 µmol l-1 and higher. These effects are probably unrelated to the inotropic effects of these substances. However, inhibition of cAMP breakdown may compensate for the adenosine-induced inhibition of adenylate cyclase and may thus at least partially explain

Wilfried Meyer; Monika Nose; Wilhelm Schmitz; Hasso Scholz

1984-01-01

48

Subclasses of External Adenosine Receptors  

Microsoft Academic Search

Cell surface adenosine receptors mediate either stimulation or inhibition of adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1], and the receptors that mediate these different responses can be discriminated with selected adenosine analogs. 5'-N-Ethylcarboxamideadenosine is a more potent agonist at stimulatory receptors (Ra) than is N6-phenylisopropyladenosine, whereas the reverse potency order is seen with inhibitory receptors (Ri). The potency of

Constantine Londos; Dermot M. F. Cooper; J. Wolff

1980-01-01

49

Adenosine receptors as drug targets  

Microsoft Academic Search

There are four adenosine receptors, A1, A2A, A2B and A3, together forming a defined subgroup of G protein coupled receptors. They are well conserved and widely expressed. The endogenous agonist, adenosine, has a minimal concentration in body fluids (20–200 nM) that is sufficient to slightly activate the receptors where they are very highly expressed—as in the basal ganglia, on fat cells

Bertil B. Fredholm

2010-01-01

50

Adenosine receptors interacting proteins (ARIPs): Behind the biology of adenosine signaling  

Microsoft Academic Search

Adenosine is a well known neuromodulator in the central nervous system. As a consequence, adenosine can be beneficial in certain disorders and adenosine receptors will be potential targets for therapy in a variety of diseases. Adenosine receptors are G protein-coupled receptors, and are also expressed in a large variety of cells and tissues. Using these receptors as a paradigm of

Francisco Ciruela; Catarina Albergaria; Aroa Soriano; Laura Cuffí; Lourdes Carbonell; Silvia Sánchez; Jorge Gandía; Víctor Fernández-Dueñas

2010-01-01

51

Adenosine induced coronary spasm – A rare presentation  

PubMed Central

Adenosine is commonly used as a pharmacological agent in myocardial perfusion imaging, as an antiarrhythmic agent, and in Cath Lab. during PCI for treating no reflow phenomenon. Coronary spasm has been reported following adenosine injection during stress imaging. We report a rare complication with ST segment elevation, following adenosine injection, given for treatment of supraventricular tachycardia. PMID:24581102

Arora, P.; Bhatia, V.; Arora, M.; Kaul, U.

2014-01-01

52

Xanthines as Adenosine Receptor Antagonists  

PubMed Central

The natural plant alkaloids caffeine and theophylline were the first adenosine receptor (AR) antagonists described in the literature. They exhibit micromolar affinities and are non-selective. A large number of derivatives and analogs have subsequently been synthesized and evaluated as AR antagonists. Very potent antagonists have thus been developed with selectivity for each of the four AR subtypes. PMID:20859796

Jacobson, Kenneth A.

2013-01-01

53

Adenosine modulation of neurotransmission in penile erection.  

PubMed Central

1. Adenosine inhibited the noradrenaline-induced contraction of rabbit corpus cavernosum in a dose-dependent manner. The effect of adenosine was greater in intact corpus cavernosa than in endothelium-denuded preparations. This finding indicates that the relaxing effect of adenosine is partially endothelium-dependent and involved in the release of endothelium-derived relaxing factors. 2. Adenosine and its analogues relaxed the noradrenaline-induced contractile response as well as inhibited the transmural nerve induced contraction with the potency order: NECA > R-PIA > adenosine. These data indicate that adenosine can modulate both the non-adrenergic non-cholinergic and adrenergic neurotransmission. DMPX, an adenosine antagonist selective for the A2 receptors, abolished the electrically elicited relaxation. However, CGS 21680, selective for A2a receptor, had no effect on relaxation. Therefore, adenosine receptors involved in the modulation of neurotransmission in rabbit corpus cavernosum appear to be A2b subtype. 3. Adenosine also induced an increase in human cavernosal arterial velocity and resistive index measured by colour duplex sonography. The combination of adenosine and 10 micrograms prostaglandin E1 was more effective in resistive index and erection grade than 20 micrograms prostaglandin E1 alone. Our results suggest that adenosine seems to be an important neuromodulator for penile erection and can be an effective and alternative combination in the treatment of impotence. PMID:7833226

Chiang, P H; Wu, S N; Tsai, E M; Wu, C C; Shen, M R; Huang, C H; Chiang, C P

1994-01-01

54

Regulation of adenosine levels during cerebral ischemia  

PubMed Central

Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events, and attenuates the excitotoxic neuronal injury. Adenosine is produced both intracellularly and extracellularly, and nucleoside transport proteins transfer adenosine across plasma membranes. Adenosine levels and receptor-mediated effects of adenosine are regulated by intracellular ATP consumption, cellular release of ATP, metabolism of extracellular ATP (and other adenine nucleotides), adenosine influx, adenosine efflux and adenosine metabolism. Recent studies have used genetically modified mice to investigate the relative contributions of intra- and extracellular pathways for adenosine formation. The importance of cortical or hippocampal neurons as a source or a sink of adenosine under basal and hypoxic/ischemic conditions was addressed through the use of transgenic mice expressing human equilibrative nucleoside transporter 1 (hENT1) under the control of a promoter for neuron-specific enolase. From these studies, we conclude that ATP consumption within neurons is the primary source of adenosine in neuronal cultures, but not in hippocampal slices or in vivo mice exposed to ischemic conditions. PMID:23064722

Chu, Stephanie; Xiong, Wei; Zhang, Dali; Soylu, Hanifi; Sun, Chao; Albensi, Benedict C; Parkinson, Fiona E

2013-01-01

55

Adenosine and adenosine analogues stimulate adenosine cyclic 3', 5'-monophosphate-dependent chloride secretion in the mammalian ileum.  

PubMed Central

Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. The purpose of these investigations was to determine the effect of adenosine on ion transport in rabbit ileum in vitro. Adenosine and some of its analogues were found to increase the short circuit current (Isc) and the order of potency was N-ethylcarboxamide-adenosine greater than or equal to 2-chloroadenosine greater than phenylisopropyladenosine greater than adenosine. Purine-intact adenosine analogues had no effect on Isc. The effect of adenosine on Isc was enhanced by deoxycoformycin, an adenosine deaminase inhibitor, and by dipyridamole, an adenosine uptake inhibitor. The increase in Isc induced by 2-chloroadenosine was partially reversed in a dose-dependent manner by 8-phenyltheophylline but not by theophylline or isobutylmethylxanthine. 2-Chloroadenosine increased cyclic AMP content, and stimulated net Cl secretion; these effects were partially blocked by 8-phenyltheophylline. These results suggest that there is an adenosine receptor on rabbit ileal mucosal cells that stimulates adenylate cyclase, which results in secondary active Cl secretion. PMID:6206092

Dobbins, J W; Laurenson, J P; Forrest, J N

1984-01-01

56

Adenosine triphosphate as a neurotransmitter and neuromodulator Geoffrey Burnstock  

E-print Network

Adenosine triphosphate as a neurotransmitter and neuromodulator Geoffrey Burnstock The first hint that adenosine triphosphate (ATP) might be a neurotransmitter came in 1954 from Holton and Holton, who presented are more responsive to adenosine and adenosine monophosphate (AMP) than to ATP and adenosine diphosphate

Burnstock, Geoffrey

57

Adenosine receptors in cerebral ischemia.  

PubMed

Ischemic stroke is a complex pathology characterized by a sequence of events that evolve over time and space. It is the second leading cause of death and the main cause of adult long-term disability in developed countries. At the moment, there is no promising pharmacotherapy for acute ischemic stroke. Adenosine receptors (A1, A2A, A2B, A3) are important targets for therapeutic implementation in the treatment of stroke because extracellular adenosine concentrations increase dramatically soon after ischemia. Adenosine receptors located both on central nervous system cells and on immune blood cells exert important roles during ischemia. The neuroprotective role of adenosine through A1 receptor subtype during ischemia is accepted, but the use of selective A1 agonists is hampered by undesirable side effects such as sedation, bradycardia, and hypotension. Recently, the A2A receptor subtype emerged as a potential therapeutic attractive target in ischemia. Evidence suggests that A2A receptor has dual role: in a first phase of ischemia, it potentiates excitotoxicity, while hours and days after ischemia, A2A receptors on immune blood cells potentiate cell adhesion mechanisms and infiltration in the ischemic parenchyma. Consistently, the use of A2A receptor agonists/antagonists (administered at doses that do not modify blood pressure and heart rate) should be carefully evaluated in function of time after ischemia. Although much is still to be known about the role of A2B and A3 receptor subtypes in brain ischemia, most consistent information indicates their role in regulation of immunosuppression and inflammation. PMID:25175971

Melani, Alessia; Pugliese, Anna Maria; Pedata, Felicita

2014-01-01

58

Magnesium Ion-dependent Activation of the RecA Protein Involves the C Terminus*  

E-print Network

Magnesium Ion-dependent Activation of the RecA Protein Involves the C Terminus* Received with ATP. We provide evi- dence that the free magnesium ion is required to medi- ate a conformational at low magnesium ion concentrations. The RecA protein of Escherichia coli plays a central role

Cox, Michael M.

59

Regulation of Macrophage Function by Adenosine  

PubMed Central

Following its release into the extracellular space in response to metabolic disturbances, the endogenous nucleoside adenosine exerts a range of immunomodulatory effects and cells of the mononuclear phagocyte system are among its major targets. Adenosine governs mononuclear phagocyte functions via 4 G-protein–coupled cell membrane receptors, which are denoted A1, A2A, A2B, and A3 receptors. Adenosine promotes osteoclast differentiation via A1 receptors and alters monocyte to dendritic cell differentiation through A2B receptors. Adenosine downregulates classical macrophage activation mainly through A2A receptors. In contrast A2B receptor activation upregulates alternative macrophage activation. Adenosine promotes angiogenesis, which is mediated by inducing the production of vascular endothelial growth factor by mononuclear phagocytes through A2A, A2B, and A3 receptors. By regulating mononuclear phagocyte function adenosine dictates the course of inflammatory and vascular diseases and cancer. PMID:22423038

Hasko, Gyorgy; Pacher, Pal

2012-01-01

60

R a Adenosine receptors in human platelets  

Microsoft Academic Search

Adenosine receptors in human platelet membranes have been characterized by radioligand binding and measurement of adenylate cyclase activity. Binding of 5'-N-ethylcarboxamido[3H]adenosine ([3H]NECA) was rapid, reversible and dependent on protein concentration, pH and temperature. Due to a rapid rate of dissociation (t1\\/2 approximately 20 s) binding was highest at 0° C. Adenosine deaminase and GTP alone did not influence [3H]NECA binding,

E. Hiittemann; D. Ukena; V. Lenschow; U. Schwabe

1984-01-01

61

Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein  

SciTech Connect

The ubiquitous adenosine A2-like binding protein obscures the binding properties of adenosine receptors assayed with 5'-N-({sup 3}H)ethylcarboxamidoadenosine (({sup 3}H)NECA). To solve this problem, we developed a rapid and simple method to separate adenosine receptors from the adenosine A2-like binding protein. Human platelet and placental membranes were solubilized with 1% 3-((3-cholamidopropyl)dimethylammonio)-1-propanesulfonate. The soluble platelet extract was precipitated with polyethylene glycol and the fraction enriched in adenosine receptors was isolated from the precipitate by differential centrifugation. The adenosine A2-like binding protein was removed from the soluble placental extract with hydroxylapatite and adenosine receptors were precipitated with polyethylene glycol. The specificity of the ({sup 3}H)NECA binding is typical of an adenosine A2 receptor for platelets and an adenosine A1 receptor for placenta. This method leads to enrichment of adenosine A2 receptors for platelets and adenosine A1 receptors for placenta. This provides a useful preparation technique for pharmacologic studies of adenosine receptors.

Zolnierowicz, S.; Work, C.; Hutchison, K.; Fox, I.H. (University Hospital, Ann Arbor, MI (USA))

1990-04-01

62

Biochemical and pharmacological characterization of periodate-oxidized adenosine analogues at adenosine A 1 receptors  

Microsoft Academic Search

Periodate oxidation of eight N6-substituted adenosine derivatives was performed with the aim of oxidizing the vicinal 2? and 3? hydroxyl groups of the ribose moiety. A thermodynamical and pharmacological characterization of the products of this transformation allowed us to verify that oxidized adenosine analogues act as agonists at adenosine A1 receptors. The dependence of their association constants on temperature indicates

Alessandro Dalpiaz; Katia Varani; Pier Andrea Borea; Claudia Martini; Grazia Chiellini; Antonio Lucacchini

1995-01-01

63

Cellular/Molecular Adenosine-Evoked Hyperpolarization of Retinal Ganglion  

E-print Network

Cellular/Molecular Adenosine-Evoked Hyperpolarization of Retinal Ganglion Cells Is Mediated by G, Minnesota 55455 Adenosine is a neuromodulator that activates presynaptic receptors to regulate synaptic transmission and postsynaptic receptors to hyperpolarize neurons. Here, we report that adenosine

Newman, Eric A.

64

21 CFR 864.7040 - Adenosine triphosphate release assay.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Adenosine triphosphate release assay. 864...Hematology Kits and Packages § 864.7040 Adenosine triphosphate release assay. (a) Identification. An adenosine triphosphate release assay is a...

2011-04-01

65

Clinical application of adenosine and ATP for pain control  

Microsoft Academic Search

This review summarizes clinical application of adenosine and adenosine 5?-triphosphate (ATP) in pain conditions. Investigations have been performed in patients with acute perioperative pain or chronic neuropathic pain treated with intravenous adenosine or ATP, or intrathecal adenosine. Characteristic central adenosine A1 receptor-mediated pain-relieving effects have been observed after intravenous adenosine infusion in human inflammation\\/sensitization pain models and in patients with

Masakazu Hayashida; Ken-ichi Fukuda; Atsuo Fukunaga

2005-01-01

66

Adenosine, energy metabolism and sleep homeostasis.  

PubMed

Adenosine is directly linked to the energy metabolism of cells. In the central nervous system (CNS) an increase in neuronal activity enhances energy consumption as well as extracellular adenosine concentrations. In most brain areas high extracellular adenosine concentrations, through A1 adenosine receptors, decrease neuronal activity and thus the need for energy. Adenosine may be a final common pathway for various sleep factors. We have identified a relatively specific area, the basal forebrain (BF), which appears to be central in the regulation/execution of recovery sleep after sleep deprivation (SD), or prolonged wakefulness. Adenosine concentration increases in this area during SD, and this increase induces sleep while prevention of the increase during SD abolishes recovery sleep. The increase in adenosine is associated with local changes in energy metabolism as indicated by increases in levels of pyruvate and lactate and increased phosphorylation of AMP-activated protein kinase. The increases in adenosine and sleep are associated with intact cholinergic system since specific lesion of the BF cholinergic cells abolishes both. Whether adenosine during SD is produced by the cholinergic neurons or astrocytes associated with them remains to be explored. An interesting, but so far unexplored question regards the relationship between the local, cortical regulation of sleep homeostasis and the global regulation of the state of sleep as executed by lower brain mechanisms, including the BF. The increase in adenosine concentration during SD also in cortical areas suggests that adenosine may have a role in the local regulation of sleep homeostasis. The core of sleep need is probably related to primitive functions of life, like energy metabolism. It can be noted that this assumption in no way excludes the possibility that later in evolution additional functions may have developed, e.g., related to complex neuronal network functions like memory and learning. PMID:20970361

Porkka-Heiskanen, Tarja; Kalinchuk, Anna V

2011-04-01

67

Enzymatic regeneration of adenosine triphosphate cofactor  

NASA Technical Reports Server (NTRS)

Regenerating adenosine triphosphate (ATP) from adenosine diphosphate (ADP) by enzymatic process which utilizes carbamyl phosphate as phosphoryl donor is technique used to regenerate expensive cofactors. Process allows complex enzymatic reactions to be considered as candidates for large-scale continuous processes.

Marshall, D. L.

1974-01-01

68

Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins  

Microsoft Academic Search

Resveratrol, a phytoalexin (3, 4?, 5, trihydroxystilbene) present in some red wines, has been reported to inhibit copper-mediated low-density lipoprotein (LDL) oxidation. In this study, we examined the efficiency of this compound in inhibiting metal ion-dependent and independent peroxidation of porcine LDL. At 0.5, 1, or 1.5 ?M, transresveratrol prolonged the lag time preceding the onset of conjugated diene formation

Leila Belguendouz; Lucie Fremont; Alain Linard

1997-01-01

69

Blocking of sodium and potassium ion-dependent adenosine triphosphatase-?1 with ouabain and vanadate suppresses cell-cell fusion during RANKL-mediated osteoclastogenesis.  

PubMed

To examine the possible enrolment of Na(+)/K(+)-ATPase during osteoclast differentiation, Na(+)/K(+)-ATPase inhibitors, including ouabain and vanadate, were used in this study. These inhibitors significantly inhibited cell-cell fusion of RAW264.7 cells and bone marrow cells induced by RANKL. Interestingly, in response to RANKL-stimulation, ouabain and vanadate decreased the number of large TRAP+ osteoclasts in the culture of RAW264.7 cells, as well as bone marrow cells. In contrast, the number of small TRAP+ osteoclasts either increased in RAW264.7 cells or were otherwise less affected in bone marrow cells than large TRAP+ osteoclasts. Large TRAP+ osteoclasts are defined as having ? 10 nuclei/cell and having more potency in bone resorption than small multinuclear osteoclasts with <9 nuclei/cell. Na(+)/K(+)-ATPase ?1 and ?2 mRNAs were detected in sRANKL-stimulated RAW264.7 cells. Moreover, real-time quantitative PCR showed that ouabain and vanadate suppressed the RANKL-dependent induction of the osteoclast fusion-promotion molecule DC-STAMP at the mRNA level. Finally, and importantly, RNAi-mediated suppression of Na(+)/K(+)-ATPase ?1 resulted in a diminished number of large TRAP+ osteoclasts in the sRANKL-stimulated RAW264.7 cells, along with the decreased level of DC-STAMP mRNA expression. These findings strongly suggest that blockage of the Na(+)/K(+)-ATPase ?1 subunit by ouabain or vanadate caused the inhibition of RANKL-induced cell-cell fusion, resulting in the generation of large osteoclasts through suppression of DC-STAMP expression. Thus, in addition to its known function of sodium and potassium ion exchange during bone resorption by mature osteoclasts, this study has revealed a novel molecular role of the Na(+)/K(+)-ATPase ?1 subunit in osteoclastogenesis. PMID:21945676

Makihira, Seicho; Nikawa, Hiroki; Kajiya, Mikihito; Kawai, Toshihisa; Mine, Yuichi; Kosaka, Eduardo; Silva, Marcelo J B; Tobiume, Kei; Terada, Yoshihiro

2011-11-30

70

Adenosine is crucial for deep brain stimulationmediated attenuation of tremor  

E-print Network

Adenosine is crucial for deep brain stimulation­mediated attenuation of tremor Lane Bekar1, resulting in accumulation of its catabolic product, adenosine. Adenosine A1 receptor activation depresses infusion of A1 receptor agonists directly reduces tremor, whereas adenosine A1 receptor­null mice show

Newman, Eric A.

71

Effect of theophylline on adenosine production in the canine myocardium  

Microsoft Academic Search

Adenosine is thought to participate in local regulation of coronary blood flow. However, competitive antagonists of adenosine fail to block myocardial active hyperemia. The authors examined the effect of locally administered theophylline on active hyperemia and myocardial adenosine production during intracoronary isoproterenol infusion in the dog heart. Isoproterenol decreased coronary resistance and increased myocardial adenosine production. Infusion of theophylline at

J. E. McKenzie; R. P. Steffen; F. J. Haddy

1987-01-01

72

The roles of adenosine and related substances in exercise hyperaemia  

Microsoft Academic Search

The role of adenosine in exercise hyperaemia has been controversial. Accumulating evidence now demonstrates that adenosine is released into the venous efflux of exercising muscle and that adenosine is responsible for 20-40% of the maintained phase of the muscle vasodilatation that accompanies submaximal and maximal contractions. This adenosine is mainly generated from AMP that is released from the skeletal muscle

Janice M. Marshall

2007-01-01

73

Regulation of cell proliferation by the guanosine-adenosine mechanism: role of adenosine receptors  

PubMed Central

A recent study (American Journal of Physiology – Cell Physiology 304:C406–C421, 2013) suggests that extracellular guanosine increases extracellular adenosine by modifying the disposition of extracellular adenosine (“guanosine–adenosine mechanism”) and that the guanosine–adenosine mechanism is not mediated by classical adenosine transport systems (SLC28 and SLC29 families) nor by classical adenosine-metabolizing enzymes. The present investigation had two aims (1) to test the hypothesis that the “guanosine–adenosine mechanism” affects cell proliferation; and (2) to determine whether the transporters SLC19A1, SLC19A2, SLC19A3, or SLC22A2 (known to carrier guanosine analogs) might be responsible for the guanosine–adenosine mechanism. In the absence of added adenosine, guanosine had little effect on the proliferation of coronary artery vascular smooth muscle cells (vascular conduit cells) or preglomerular vascular smooth muscle cells (vascular resistance cells). However, in the presence of added adenosine (3 or 10 ?mol/L), guanosine (10–100 ?mol/L) decreased proliferation of both cell types, thus resulting in a highly significant (P < 0.000001) interaction between guanosine and adenosine on cell proliferation. The guanosine–adenosine interaction on cell proliferation was abolished by 1,3-dipropyl-8-(p-sulfophenyl)xanthine (adenosine receptor antagonist). Guanosine (30 ?mol/L) increased extracellular levels of adenosine when adenosine (3 ?mol/L) was added to the medium. This effect was not reproduced by high concentrations of methotrexate (100 ?mol/L), thiamine (1000 ?mol/L), chloroquine (1000 ?mol/L), or acyclovir (10,000 ?mol/L), archetypal substrates for SLC19A1, SLC19A2, SLC19A3, and SLC22A2, respectively; and guanosine still increased adenosine levels in the presence of these compounds. In conclusion, the guanosine–adenosine mechanism affects cell proliferation and is not mediated by SLC19A1, SLC19A2, SLC19A3, or SLC22A2. PMID:23956837

Jackson, Edwin K; Gillespie, Delbert G

2013-01-01

74

Adenosine Kinase: Exploitation for Therapeutic Gain  

PubMed Central

Adenosine kinase (ADK; EC 2.7.1.20) is an evolutionarily conserved phosphotransferase that converts the purine ribonucleoside adenosine into 5?-adenosine-monophosphate. This enzymatic reaction plays a fundamental role in determining the tone of adenosine, which fulfills essential functions as a homeostatic and metabolic regulator in all living systems. Adenosine not only activates specific signaling pathways by activation of four types of adenosine receptors but it is also a primordial metabolite and regulator of biochemical enzyme reactions that couple to bioenergetic and epigenetic functions. By regulating adenosine, ADK can thus be identified as an upstream regulator of complex homeostatic and metabolic networks. Not surprisingly, ADK dysfunction is involved in several pathologies, including diabetes, epilepsy, and cancer. Consequently, ADK emerges as a rational therapeutic target, and adenosine-regulating drugs have been tested extensively. In recent attempts to improve specificity of treatment, localized therapies have been developed to augment adenosine signaling at sites of injury or pathology; those approaches include transplantation of stem cells with deletions of ADK or the use of gene therapy vectors to downregulate ADK expression. More recently, the first human mutations in ADK have been described, and novel findings suggest an unexpected role of ADK in a wider range of pathologies. ADK-regulating strategies thus represent innovative therapeutic opportunities to reconstruct network homeostasis in a multitude of conditions. This review will provide a comprehensive overview of the genetics, biochemistry, and pharmacology of ADK and will then focus on pathologies and therapeutic interventions. Challenges to translate ADK-based therapies into clinical use will be discussed critically. PMID:23592612

2013-01-01

75

Adenosine receptors as drug targets--what are the challenges?  

PubMed

Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors--either directly or indirectly--have now entered the clinic. However, only one adenosine receptor-specific agent--the adenosine A2A receptor agonist regadenoson (Lexiscan; Astellas Pharma)--has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges. PMID:23535933

Chen, Jiang-Fan; Eltzschig, Holger K; Fredholm, Bertil B

2013-04-01

76

Adenosine receptors as drug targets -- what are the challenges?  

PubMed Central

Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors — either directly or indirectly — have now entered the clinic. However, only one adenosine receptor-specific agent — the adenosine A2A receptor agonist regadenoson (Lexiscan; Astellas Pharma) — has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges. PMID:23535933

Chen, Jiang-Fan; Eltzschig, Holger K.; Fredholm, Bertil B.

2014-01-01

77

Adenosine deaminase affects ligand-induced signalling by interacting with cell surface adenosine receptors  

Microsoft Academic Search

Adenosine deaminase (ADA) is not only a cytosolic enzyme but can be found as an ecto-enzyme. At the plasma membrane, an adenosine deaminase binding protein (CD26, also known as dipeptidylpeptidase IV) has been identified but the functional role of this ADA\\/CD26 complex is unclear. Here by confocal microscopy, affinity chromatography and coprecipitation experiments we show that A1 adenosine receptor (A1R)

Francisco Ciruela; Carles Saura; Enric I. Canela; Josefa Mallol; Carmen Lluis; Rafael Franco

1996-01-01

78

Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons  

PubMed Central

Adenosine has been proposed as an endogenous homeostatic sleep factor that accumulates during waking and inhibits wake-active neurons to promote sleep. It has been specifically hypothesized that adenosine decreases wakefulness and promotes sleep recovery by directly inhibiting wake-active neurons of the basal forebrain (BF), particularly BF cholinergic neurons. We previously showed that adenosine directly inhibits BF cholinergic neurons. Here, we investigated 1) how adenosine modulates glutamatergic input to BF cholinergic neurons and 2) how adenosine uptake and adenosine metabolism are involved in regulating extracellular levels of adenosine. Our experiments were conducted using whole cell patch-clamp recordings in mouse brain slices. We found that in BF cholinergic neurons, adenosine reduced the amplitude of AMPA-mediated evoked glutamatergic excitatory postsynaptic currents (EPSCs) and decreased the frequency of spontaneous and miniature EPSCs through presynaptic A1 receptors. Thus we have demonstrated that in addition to directly inhibiting BF cholinergic neurons, adenosine depresses excitatory inputs to these neurons. It is therefore possible that both direct and indirect inhibition may synergistically contribute to the sleep-promoting effects of adenosine in the BF. We also found that blocking the influx of adenosine through the equilibrative nucleoside transporters or inhibiting adenosine kinase and adenosine deaminase increased endogenous adenosine inhibitory tone, suggesting a possible mechanism through which adenosine extracellular levels in the basal forebrain are regulated. PMID:22357797

Hawryluk, J. M.; Ferrari, L. L.; Keating, S. A.

2012-01-01

79

Adenosine--a physiological or pathophysiological agent?  

PubMed

This minireview briefly summarizes the evidence that adenosine, acting on four G-protein coupled receptors, can play physiological roles, but is also critically involved in pathological processes. The factors that decide which of these is the more important in a specific cell or organ are briefly summarized. The fact that drugs that target adenosine receptors in disease will also hit the physiological processes will make drug development more tricky. PMID:24362516

Fredholm, Bertil B

2014-03-01

80

Gas-Phase Protonation Thermochemistry of Adenosine  

Microsoft Academic Search

The goal of this work was to obtain a detailed insight on the gas-phase protonation energetic of adenosine using both mass spectrometric experiments and quantum chemical calculations. The experimental approach used the extended kinetic method with nanoelectrospray ionization and collision-induced dissociation tandem mass spectrometry. This method provides experimental values for proton affinity, PA(adenosine) ) 979 ( 1 kJ ·mol-1, and

David Touboul; Guy Bouchoux; Renato Zenobi

2008-01-01

81

Inverse agonism at adenosine A 1 receptors  

Microsoft Academic Search

Inverse agonism at adenosine A1 receptors was studied in a variety of experimental set-ups. As a read-out, the binding of [35S]GTP?S to membranes of either CHO or COS-7 cells expressing human adenosine A1 receptors was used. When wild-type receptors were studied, inverse agonism could only be detected at higher levels of receptor expression. However, receptors fused with (mutated) ?-subunits of

Rianne A. F de Ligt; Anna Lorenzen; Adriaan P IJzerman

2003-01-01

82

Role of adenosine receptors in caffeine tolerance  

SciTech Connect

Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity.

Holtzman, S.G.; Mante, S.; Minneman, K.P. (Emory Univ. School of Medicine, Atlanta, GA (USA))

1991-01-01

83

Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium  

SciTech Connect

Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium the authors found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. The observation that mucosal 8-phenyletheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.

Pratt, A.D.; Clancy, G.; Welsh, M.J.

1986-08-01

84

Caffeine, adenosine receptors, and synaptic plasticity.  

PubMed

Few studies to date have looked at the effects of caffeine on synaptic plasticity, and those that did used very high concentrations of caffeine, whereas the brain concentrations attained by regular coffee consumption in humans should be in the low micromolar range, where caffeine exerts pharmacological actions mainly by antagonizing adenosine receptors. Accordingly, rats drinking caffeine (1 g/L) for 3 weeks, displayed a concentration of caffeine of circa 22 microM in the hippocampus. It is known that selective adenosine A1 receptor antagonists facilitate, whereas selective adenosine A2A receptor antagonists attenuate, long term potentiation (LTP) in the hippocampus. Although caffeine is a non-selective antagonist of adenosine receptors, it attenuates frequency-induced LTP in hippocampal slices in a manner similar to selective adenosine A2A receptor antagonists. These effects of low micromolar concentration of caffeine (30 microM) are maintained in aged animals, which is important when a possible beneficial effect for caffeine in age-related cognitive decline is proposed. Future studies will still be required to confirm and detail the involvement of A1 and A2A receptors in the effects of caffeine on hippocampal synaptic plasticity, using both pharmacological and genetic approaches. PMID:20182030

Costenla, Ana Rita; Cunha, Rodrigo A; de Mendonça, Alexandre

2010-01-01

85

A new class of adenosine receptors in brain: Characterization by 2-chloro( sup 3 H)adenosine binding  

SciTech Connect

Considerable evidence has accumulated in recent years to support a role for adenosine as an important physiological modulator in many mammalian tissues. In brain, adenosine is a potent depressant of neuronal firing and synaptic transmission. The exact mechanisms by which adenosine analogs depress nerve cell activity in the brain are not clear. Despite considerable investigation, neither the A1 nor the A2 adenosine receptors associated with adenylate cyclase have been able to account adequately for the actions of adenosine in brain. It has been proposed that additional adenosine receptors, possibly linked to calcium channels, are present in the central nervous system and are responsible for the physiological actions of adenosine. In this thesis, evidence is provided for the existence of a novel class of adenosine receptors in rat brain. The methods used to identify this new class of receptors involved radioligand binding techniques which have been successfully employed to characterize the properties of many neurotransmitter and drug receptors. 2-Chloro({sup 3}H)adenosine (Cl({sup 3}H)Ado) was selected as the ligand for these experiments since is a water-soluble, metabolically-stable analog of adenosine and a potent depressant of synaptic transmission in brain. The results demonstrate the presence of a distinct class of 2-chloro({sup 3}H)adenosine binding sites in rat forebrain membranes with an apparent K{sub D} of about 10 {mu}M and a B{sub max} of about 60 pmol per mg of protein. Specific 2-chloro ({sup 3}H)adenosine binding is highly specific for adenosine agonists and antagonists. Inhibition of binding by adenosine agonists exhibits an order of potency 2-chloroadenosine > 5{prime}-N-ethylcarboxamide adenosine > ({minus})-N{sup 6}-(R-phenylisopropyl)adenosine, which differs from that of both A1 and A2 adenosine receptors.

Chin, Jerome Hsicheng.

1988-01-01

86

Novel adenosine receptors in rat hippocampus identification and characterization  

SciTech Connect

2-chloro(/sup 3/H)adenosine, a stable analog of adenosine, was used to investigate the presence of adenosine receptors in rat hippocampal membranes that may mediate the depressant effects of adenosine on synaptic transmission in this tissue. Equilibrium binding studies reveal the presence of a previously undescribed class of receptors with a K/sub D/ of 4.7 ..mu..M and a Bmax of 130 pmol/mg of protein. Binding is sensitive to alkylxanthines and to a number of adenosine-related compounds. The pharmacological properties of this binding site are distinct from those of the A1 and A2 adenosine receptors associated with adenylate cyclase. The results suggest that this adenosine binding site is a novel central purinergic receptor through which adenosine may regulate hippocampal excitability. 50 references, 2 figures, 1 table.

Chin, J.H.; Mashman, W.E.; DeLorenzo, R.J.

1985-05-06

87

Adenosine in vertebrate retina: Localization, receptor characterization, and function  

Microsoft Academic Search

1.The uptake of [3H] adenosine into specific populations of cells in the inner retina has been demonstrated. In mammalian retina, the exogenous adenosine that is transported into cells is phosphorylated, thereby maintaining a gradient for transport of the purine into the cell.2.Endogenous stores of adenosine have been demonstrated by localization of cells that are labeled for adenosine-like immunoreactivity. In the

Christine Blazynski; Maria-Thereza R. Perez

1991-01-01

88

Adenosine — A peripheral neuronal modulator of pain and inflammation  

Microsoft Academic Search

\\u000a In the central nervous system, adenosine plays an important physiological role in the regulation of neuronal activity and\\u000a in neuroprotection. Adenosine actions are mediated by cell surface adenosine receptors (A1, A2A, A2B, A3) which are all linked to G-proteins, and activation of these receptors can recruit a number of second messenger systems [1,2] (Tab. 1). Adenosine has a high affinity

Jana Sawynok

89

Adenosine and ATP receptors in the brain.  

PubMed

There is a widespread presence of both adenosine (P1) and P2 nucleotide receptors in the brain on both neurones and glial cells. Adenosine receptors play a major role in presynaptic neuromodulation, while P2X receptors are involved in fast synaptic transmission and synaptic plasticity. P2Y receptors largely mediate presynaptic activities. Both P1 and P2 receptors participate in neurone-glia interactions. Purinergic signalling is involved in control of cerebral vascular tone and remodelling. Examples of the roles of purinoceptors in neuropathology involve: A(2A) receptors in Parkinson's disease and epilepsy, P2 receptors in trauma, ischaemia. Neuroinflammatory and neuropsychiatric disorders, and neuropathic pain. PMID:21401499

Burnstock, Geoffrey; Fredholm, Bertil B; Verkhratsky, Alexei

2011-01-01

90

Two Distinct Adenosine-Sensitive Sites on Adenylate Cyclase  

Microsoft Academic Search

The effects of adenosine and adenosine analogs on adenylate cyclases from several tissues have been examined. Two adenosine-reactive sites have been identified: (i) the ``R'' site, occupancy of which usually leads to activation of cyclase and which requires integrity of the ribose ring for activity, and (ii) the ``P'' site, which mediates inhibition and requires integrity of the purine ring

Constantine Londos; J. Wolff

1977-01-01

91

ORIGINAL RESEARCH Open Access Cardioprotective effects of adenosine within the  

E-print Network

ORIGINAL RESEARCH Open Access Cardioprotective effects of adenosine within the border and remote,5 and Yvan Devaux1* Abstract Background: Adenosine may have beneficial effects on left ventricular function is controversial. We assessed the long-term effects of adenosine after MI using electrocardiogram-triggered 18 F

Paris-Sud XI, Université de

92

CD39/Adenosine Pathway Is Involved in AIDS Progression  

E-print Network

CD39/Adenosine Pathway Is Involved in AIDS Progression Maria Nikolova1,2. , Matthieu Carriere139/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects

Paris-Sud XI, Université de

93

ORAL PRESENTATION Open Access Double-stranded RNA adenosine deaminase  

E-print Network

ORAL PRESENTATION Open Access Double-stranded RNA adenosine deaminase ADAR1 enhances both T cell), an inhibitor of viral mRNA translation, and the double-stranded RNA adenosine deaminase ADAR1. ADAR1 has the ability to convert adenosine (A) into guanosine (G), thereby introducing mutations in the viral genome

Paris-Sud XI, Université de

94

Regulation of adenosine transport by acute and chronic ethanol exposure  

SciTech Connect

Chronic exposure to ethanol results in a desensitization of adenosine receptor-stimulated cAMP production. Since adenosine is released by cells and is known to desensitize its own as well as other receptors, it may be involved in ethanol-induced desensitization of adenosine receptor function. Therefore, we have examine the acute and chronic effects of ethanol on the transport of adenosine via the nucleoside transport. Acute exposure to ethanol caused an inhibition of adenosine uptake in S49 lymphoma cells. This decrease in uptake resulted in accumulation of extracellular adenosine after ethanol exposure. The effect of ethanol was specific to nucleoside transport. Uptake of uridine, also transported by the nucleoside transporter, was inhibited by ethanol to the same degree as adenosine uptake, while neither isoleucine nor deoxyglucose uptake was altered by ethanol treatment. Inhibition of adenosine uptake by ethanol was non-competitive and dependent on the concentration of ethanol. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol. There was no longer an acute inhibition of adenosine uptake, nor was these accumulation of extracellular adenosine. Chronic ethanol exposure also resulted in a decrease in the absolute rate of adenosine uptake. Binding studies using a high affinity lignad for the nucleoside transporter, nitrobenzylthioinosine (NBMPR), indicate that this decreased uptake was due to a decrease in the maximal number of binding sites. These ethanol-induced changes in adenosine transport may be important for the acute and chronic effects of ethanol.

Nagy, L.E.; Casso, D.; Diamond, I.; Gordon, A.S. (Univ. of California, San Francisco (USA))

1989-02-09

95

A Role for Adenosine Deaminase in Drosophila Larval Development  

Microsoft Academic Search

Adenosine deaminase (ADA) is an enzyme present in all organisms that catalyzes the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine. Both adenosine and deoxyadenosine are biologically active purines that can have a deep impact on cellular physiology; notably, ADA deficiency in humans causes severe combined immunodeficiency. We have established a Drosophila model to study the effects of

Tomas Dolezal; Eva Dolezelova; Michal Zurovec; Peter J. Bryant

2005-01-01

96

Adenosine inhibits IL12 and TNF-a production via adenosine A2a receptor-dependent and independent mechanisms  

Microsoft Academic Search

Interleukin 12 (IL-12) is a crucial cyto- kine in the regulation of T helper 1 vs. T helper 2 immune responses. In the present study, we investi- gated the effect of the endogenous purine nucleo- side adenosine on the production of IL-12. In mouse macrophages, adenosine suppressed IL-12 produc- tion. Although the order of potency of adenosine receptor agonists suggested

GYORGY HASKO; DAVID G. KUHEL; JIANG-FAN CHEN; MICHAEL A. SCHWARZSCHILD; EDWIN A. DEITCH; JON G. MABLEY; ANITA MARTON; CSABA SZABO ´

97

Shaping of monocyte and macrophage function by adenosine receptors.  

PubMed

Adenosine is an endogenous purine nucleoside that, following its release into the extracellular space, binds to specific adenosine receptors expressed on the cell surface. Adenosine appears in the extracellular space under metabolically stressful conditions, which are associated with ischemia, inflammation, and cell damage. There are 4 types of adenosine receptors (A(1), A(2A), A(2B) and A(3)) and all adenosine receptors are members of the G protein-coupled family of receptors. Adenosine receptors are expressed on monocytes and macrophages and through these receptors adenosine modulates monocyte and macrophage function. Since monocytes and macrophages are activated by the same danger signals that cause accumulation of extracellular adenosine, adenosine receptors expressed on macrophages represent a sensor system that provide monocytes and macrophages with information about the stressful environment. Adenosine receptors, thus, allow monocytes and macrophages to fine-tune their responses to stressful stimuli. Here, we review the consequences of adenosine receptor activation on monocyte/macrophage function. We will detail the effect of stimulating the various adenosine receptor subtypes on macrophage differentiation/proliferation, phagocytosis, and tissue factor (TF) expression. We will also summarize our knowledge of how adenosine impacts the production of extracellular mediators secreted by monocytes and macrophages in response to toll-like receptor (TLR) ligands and other inflammatory stimuli. Specifically, we will delineate how adenosine affects the production of superoxide, nitric oxide (NO), tumor necrosis factor-alpha, interleukin (IL)-12, IL-10, and vascular endothelial growth factor (VEGF). A deeper insight into the regulation of monocyte and macrophage function by adenosine receptors should assist in developing new therapies for inflammatory diseases. PMID:17056121

Haskó, György; Pacher, Pál; Deitch, Edwin A; Vizi, E Sylvester

2007-02-01

98

Gonadotropins Regulate Inducible Cyclic Adenosine 3 ,5 -  

E-print Network

Gonadotropins Regulate Inducible Cyclic Adenosine 3 ,5 - Monophosphate Early Repressor in the Rat of CREM might have a role in the LH-mediated suppression of inhibin -subunit gene expression that occurs (ICER). ICER mRNAs are strongly induced in the ovary by exogenous gonadotropins in immature rats

Mayo, Kelly E.

99

Genetics Home Reference: Adenosine deaminase deficiency  

MedlinePLUS

... past age 2. In about 10 percent to 15 percent of cases, onset of immune deficiency is delayed to between ... newborns worldwide. This disorder is responsible for approximately 15 percent of SCID cases. What genes are related to ADA deficiency? Adenosine ...

100

Folding Study of Venus Reveals a Strong Ion Dependence of Its Yellow Fluorescence under Mildly Acidic Conditions*S  

E-print Network

Folding Study of Venus Reveals a Strong Ion Dependence of Its Yellow Fluorescence under Mildly- cencethatisrelativelyinsensitivetochangesinpHandionconcen- trations. Here, we present a detailed study of the stability and fold- ing of Venus. By following hydrogen-deuterium exchange of 15 N-labeled Venus using NMR spectroscopy over 13 months, residue

Jackson, Sophie

101

Internalization and desensitization of adenosine receptors  

PubMed Central

Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A1, A2A, A2B and A3 receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body and involved in a variety of physiological processes and diseases, there is great interest in understanding how the different subtypes are regulated, as a basis for designing therapeutic drugs that either avoid or make use of this regulation. The major GPCR regulatory pathway involves phosphorylation of activated receptors by G protein-coupled receptor kinases (GRKs), a process that is followed by binding of arrestin proteins. This prevents receptors from activating downstream heterotrimeric G protein pathways, but at the same time allows activation of arrestin-dependent signalling pathways. Upon agonist treatment, adenosine receptor subtypes are differently regulated. For instance, the A1Rs are not (readily) phosphorylated and internalize slowly, showing a typical half-life of several hours, whereas the A2AR and A2BR undergo much faster downregulation, usually shorter than 1 h. The A3R is subject to even faster downregulation, often a matter of minutes. The fast desensitization of the A3R after agonist exposure may be therapeutically equivalent to antagonist occupancy of the receptor. This review describes the process of desensitization and internalization of the different adenosine subtypes in cell systems, tissues and in vivo studies. In addition, molecular mechanisms involved in adenosine receptor desensitization are discussed. PMID:18368531

Klaasse, Elisabeth C.; de Grip, Willem J.; Beukers, Margot W.

2007-01-01

102

Regulation of Leukocyte Function by Adenosine Receptors  

PubMed Central

The immune system responds to cues in the microenvironment to make acute and chronic adaptations in response to inflammation and injury. Locally produced purine nucleotides and adenosine provide receptor-mediated signaling to all bone-marrow derived cells of the immune system to modulate their responses. This review summarizes recent advances in our understanding of the effects of adenosine signaling through G protein-coupled adenosine receptors on cells of the immune system. Adenosine A2A receptors (A2ARs) have a generally suppressive effect on the activation of immune cells. Moreover, their transcription is strongly induced by signals that activate macrophages or dendritic cells through toll-like receptors, or T cells through T cell receptors. A2AR induction is responsible for producing a gradual dissipation of inflammatory responses. A2AR activation is particularly effective in limiting the activation of invariant NKT (iNKT) cells that play a central role in acute reperfusion injury. A2A agonists have clinical promise for the treatment of vaso-occlusive tissue injury. Blockade of A2A receptors may be useful to enhance immune-mediated killing of cancer cells. A2BR expression also is transcriptionally regulated by hypoxia, cytokines, and oxygen radicals. Acute A2BR activation attenuates the production of proinflammatory cytokines from macrophages, but sustained activation facilitates macrophage and dendritic cell remodeling and the production of acute phase proteins and angiogenic factors that may participate in evoking insulin resistance and tissue fibrosis. A2BR activation also influences macrophage and neutrophil function by influencing expression of the anti-inflammatory netrin receptor, UNC5B. The therapeutic significance of adenosine-mediated effects on the immune system is discussed. PMID:21586357

Linden, Joel

2013-01-01

103

Staphylococcus aureus synthesizes adenosine to escape host immune responses  

PubMed Central

Staphylococcus aureus infects hospitalized or healthy individuals and represents the most frequent cause of bacteremia, treatment of which is complicated by the emergence of methicillin-resistant S. aureus. We examined the ability of S. aureus to escape phagocytic clearance in blood and identified adenosine synthase A (AdsA), a cell wall–anchored enzyme that converts adenosine monophosphate to adenosine, as a critical virulence factor. Staphylococcal synthesis of adenosine in blood, escape from phagocytic clearance, and subsequent formation of organ abscesses were all dependent on adsA and could be rescued by an exogenous supply of adenosine. An AdsA homologue was identified in the anthrax pathogen, and adenosine synthesis also enabled escape of Bacillus anthracis from phagocytic clearance. Collectively, these results suggest that staphylococci and other bacterial pathogens exploit the immunomodulatory attributes of adenosine to escape host immune responses. PMID:19808256

Thammavongsa, Vilasack; Kern, Justin W.; Missiakas, Dominique M.

2009-01-01

104

Adenosine Receptors: Expression, Function and Regulation  

PubMed Central

Adenosine receptors (ARs) comprise a group of G protein-coupled receptors (GPCR) which mediate the physiological actions of adenosine. To date, four AR subtypes have been cloned and identified in different tissues. These receptors have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. This review will describe the biochemical characteristics and signaling cascade associated with each receptor and provide insight into how these receptors are regulated in response to agonists. A key property of some of these receptors is their ability to serve as sensors of cellular oxidative stress, which is transmitted by transcription factors, such as nuclear factor (NF)-?B, to regulate the expression of ARs. Recent observations of oligomerization of these receptors into homo- and heterodimers will be discussed. In addition, the importance of these receptors in the regulation of normal and pathological processes such as sleep, the development of cancers and in protection against hearing loss will be examined. PMID:24477263

Sheth, Sandeep; Brito, Rafael; Mukherjea, Debashree; Rybak, Leonard P.; Ramkumar, Vickram

2014-01-01

105

Adenosine thallium 201 myocardial perfusion scintigraphy  

SciTech Connect

Pharmacologic coronary vasodilation as an adjunct to myocardial perfusion imaging has become increasingly important in the evaluation of patients with coronary artery disease, in view of the large number of patients who cannot perform an adequate exercise test or in whom contraindications render exercise inappropriate. Adenosine is a very potent coronary vasodilator and when combined with thallium 201 scintigraphy produces images of high quality, with the added advantages of a very short half-life (less than 10 seconds) and the ability to adjust the dose during the infusion, which may enhance safety and curtail the duration of side effects. The reported sensitivity and specificity of adenosine thallium 201 scintigraphy for the detection of coronary artery disease are high and at least comparable with imaging after exercise or dipyridamole administration. 23 refs.

Verani, M.S. (Baylor College of Medicine and Nuclear Cardiology, The Methodist Hospital, Houston, TX (USA))

1991-07-01

106

Adenosine infusion inhibits adenosine-induced cardiac actions but enhances acetylcholine-induced actions in isolated dog atria.  

PubMed

Using isolated, blood-perfused canine atrial preparations, adenosine was continuously administered at various infusion rates into the cannulated sinus node artery. Adenosine induced negative chrono- and inotropic effects in an infusion-rate related manner. The inotropic responses to the adenosine infusion apparently faded but the chronotropic responses did not. Effects of a bolus injection of adenosine, acetylcholine (ACh), or norepinephrine and effects of intracardiac autonomic nerve stimulation (ICNS) were examined before and during the adenosine infusion. During the adenosine infusion, adenosine-induced effects were significantly reduced but ACh-induced ones were significantly potentiated, and the norepinephrine-induced effects were slightly depressed. ICNS readily induced negative and positive chrono- and inotropic responses which were blocked by atropine and propranolol. These negative responses were enhanced but positive ones were slightly but insignificantly depressed during the adenosine infusion. From these results, it is concluded that adenosine infusion (1) produces a stable continuous bradycardia but in the developed tension an initial decrease is followed by a gradual recovery response showing the fade phenomenon, (2) causes an acute desensitizing action on a subsequent bolus dose of adenosine, and (3) induces a weak antiadrenergic effect, while enhancing cholinergic effects in isolated canine atria. PMID:12644878

Tsuboi, Masato; Chiba, Shigetoshi

2003-03-01

107

Potentiation of formalin-evoked adenosine release by an adenosine kinase inhibitor and an adenosine deaminase inhibitor in the rat hind paw: a microdialysis study  

Microsoft Academic Search

The present study examined the effects of local subcutaneous administration of formalin on adenosine release from the rat hind paw, and the effects of inhibitors of adenosine metabolism on such release. Microdialysis probes were inserted into the subcutaneous tissue of the plantar surface of rat hind paws. Samples were collected every 10 min at a perfusion rate of 2 ?l\\/min

Xue Jun Liu; Thomas D White; Jana Sawynok

2000-01-01

108

Effect of adenosine and adenosine analogs on ( sup 14 C)aminopyrine accumulation by rabbit parietal cells  

SciTech Connect

Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on (14C)aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. (14C)Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated (14C)aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on (14C)aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased (14C)aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.

Ota, S.; Hiraishi, H.; Terano, A.; Mutoh, H.; Kurachi, Y.; Shimada, T.; Ivey, K.J.; Sugimoto, T. (Univ. of Tokyo (Japan))

1989-12-01

109

The molecular mechanism of ion-dependent gating in secondary transporters.  

PubMed

LeuT-like fold Na-dependent secondary active transporters form a large family of integral membrane proteins that transport various substrates against their concentration gradient across lipid membranes, using the free energy stored in the downhill concentration gradient of sodium ions. These transporters play an active role in synaptic transmission, the delivery of key nutrients, and the maintenance of osmotic pressure inside the cell. It is generally believed that binding of an ion and/or a substrate drives the conformational dynamics of the transporter. However, the exact mechanism for converting ion binding into useful work has yet to be established. Using a multi-dimensional path sampling (string-method) followed by all-atom free energy simulations, we established the principal thermodynamic and kinetic components governing the ion-dependent conformational dynamics of a LeuT-like fold transporter, the sodium/benzyl-hydantoin symporter Mhp1, for an entire conformational cycle. We found that inward-facing and outward-facing states of Mhp1 display nearly the same free energies with an ion absent from the Na2 site conserved across the LeuT-like fold transporters. The barrier separating an apo-state from inward-facing or outward-facing states of the transporter is very low, suggesting stochastic gating in the absence of ion/substrate bound. In contrast, the binding of a Na2 ion shifts the free energy stabilizing the outward-facing state and promoting substrate binding. Our results indicate that ion binding to the Na2 site may also play a key role in the intracellular thin gate dynamics modulation by altering its interactions with the transmembrane helix 5 (TM5). The Potential of Mean Force (PMF) computations for a substrate entrance displays two energy minima that correspond to the locations of the main binding site S1 and proposed allosteric S2 binding site. However, it was found that substrate's binds to the site S1 ?5 kcal/mol more favorable than that to the site S2 for all studied bound combinations of ions and a substrate. PMID:24204233

Zhao, Chunfeng; Noskov, Sergei Yu

2013-10-01

110

Use of adenosine echocardiography for diagnosis of coronary artery disease  

SciTech Connect

Two-dimensional echocardiography combined with exercise is sensitive and specific in the detection of coronary artery disease (CAD) by demonstrating transient abnormalities in wall motion. Frequently, however, patients cannot achieve maximal exercise because of various factors. Pharmacologic stress testing with intravenous adenosine was evaluated as a means of detecting CAD in a noninvasive manner. Patients with suspected CAD underwent echocardiographic imaging and simultaneous thallium 201 single-photon emission computed tomography during the intravenous administration of 140 micrograms/kg/min of adenosine. An increase in heart rate, decrease in blood pressure, and increase in double product were observed during adenosine administration. Initial observations revealed that wall motion abnormalities were induced by adenosine in areas of perfusion defects. The adenosine infusion was well tolerated, and symptoms disappeared within 1 to 2 minutes after termination of the infusion. Therefore preliminary observations suggest that adenosine echocardiography appears to be useful in the assessment of CAD.

Zoghbi, W.A. (Section of Cardiology Baylor College of Medicine, Methodist Hospital, Houston, TX (USA))

1991-07-01

111

The role of adenosine signaling in sickle cell therapeutics.  

PubMed

Data suggest a role for adenosine signaling in the pathogenesis of sickle cell disease (SCD). Signaling through the adenosine A2A receptor (A2AR) has demonstrated beneficial effects. Activation of A2ARs decreases inflammation with SCD by blocking activation of invariant natural killer T cells. Decreased inflammation may reduce the severity of vasoocclusive crises. Adenosine signaling through the adenosine A2B receptor (A2BR) may be detrimental in SCD. Whether adenosine signaling predominantly occurs through A2ARs or A2BRs may depend on differing levels of adenosine and disease state (steady state versus crisis). There may be opportunities to develop novel therapeutic approaches targeting A2ARs and/or A2BRs for patients with SCD. PMID:24589267

Field, Joshua J; Nathan, David G; Linden, Joel

2014-04-01

112

Intravenous adenosine and lidocaine in patients with acute myocardial infarction  

Microsoft Academic Search

Objectives A pilot study was designed to assess the safety of combined intravenous adenosine lidocaine in patients with acute myocardial infarction to estimate the likelihood of a beneficial effect on final infarct size.Background Adenosine plus lidocaine reduces infarct size in animals but the safety efficacy in human beings is unknown.Methods and Results Adenosine (70 ?g\\/kg per minute intravenous infusion) plus

Kirk N. Garratt; David R. Holmes; Victor Molina-Viamonte; Guy S. Reeder; David O. Hodge; Kent R. Bailey; Joseph K. Lobl; Dennis A. Laudon; Raymond J. Gibbons

1998-01-01

113

Role of macula densa adenosine triphosphate (ATP) in tubuloglomerular feedback  

Microsoft Academic Search

Role of macula densa adenosine triphosphate (ATP) in tubuloglomerular feedback.BackgroundRecent studies have shown that adenosine triphosphate (ATP) is liberated from macula densa cells in response to increased tubular NaCl in vitro. We tested the hypothesis that increased NaCl in the macula densa stimulates the release of ATP, resulting in extracellular formation of adenosine which is involved in signal transmission of

YILIN REN; JEFFREY L GARVIN; RUISHENG LIU; OSCAR A CARRETERO

2004-01-01

114

Caffeine intensifies taste of certain sweeteners: role of adenosine receptor.  

PubMed

Caffeine, a potent antagonist of adenosine receptors, potentiates the taste of some but not all sweeteners. It significantly enhances the taste of acesulfam-K, neohesperidin dihydrochalcone, d-tryptophan, thaumatin, stevioside, and sodium saccharin. Adenosine reverses the enhancement. Caffeine has no effect on aspartame, sucrose, fructose, and calcium cyclamate. These results suggest that the inhibitory A1 adenosine receptor plays an important local role in modulating the taste intensity of certain sweeteners and that several transduction mechanisms mediate sweet taste. PMID:3010333

Schiffman, S S; Diaz, C; Beeker, T G

1986-03-01

115

Measurement of plasma adenosine concentration: methodological and physiological considerations  

SciTech Connect

This study tested the hypothesis that measurements of plasma adenosine concentration made on samples of blood obtained in dipyridamole and EHNA (i.e., stopping solution) may be falsely elevated as a result of ongoing in vitro production and accumulation of adenosine during sample processing. Studies were performed with samples of anticoagulated blood obtained from anesthesized domestic swine. Adenosine concentration of ultra filtrated plasma was determined by HPLC. The following parameters were evaluated: (i) rate of clearance of (/sup 3/H)adenosine added to plasma, (ii) endogenous adenosine concentration of matched blood samples obtained in stopping solution alone, stopping solution plus EDTA, and perchloric acid (PCA), (iii) plasma and erythrocyte endogenous adenosine concentration in nonhemolyzed samples, and (iv) plasma adenosine concentration of samples hemolyzed in the presence of stopping solution alone or stopping solution plus EDTA. We observed that (i) greater than or equal to 95% of (/sup 3/H)adenosine added to plasma is removed from it by formed elements of the blood in less than 20 s, (ii) plasma adenosine concentration of samples obtained in stopping solution alone is generally 10-fold greater than that of matched samples obtained in stopping solution plus EDTA, (iii) deliberate mechanical hemolysis of blood samples obtained in stopping solution alone resulted in substantial augmentation of plasma adenosine levels in comparison with matched nonhemolyzed specimens--addition of EDTA to stopping solution prevented this, and (iv) adenosine content of blood samples obtained in PCA agreed closely with the sum of plasma and erythrocyte adenosine content of samples obtained in stopping solution plus EDTA.

Gewirtz, H.; Brown, P.; Most, A.S.

1987-05-01

116

Turnover of adenosine in plasma of human and dog blood  

SciTech Connect

To determine half-life and turnover of plasma adenosine, heparinized blood from healthy volunteers was incubated with radiolabeled adenosine in the physiological concentration range of 0.1-1 microM. Plasma levels of adenosine in vitro were 82 +/- 14 nM and were similar to those determined immediately after blood collection with a ''stopping solution.'' Dipyridamole (83 microM) and erythro-9(2-hydroxynon-3yl)-adenine (EHNA) (8 microM) did not measurably alter basal adenosine levels but completely blocked the uptake of added adenosine. Inhibition of ecto-5'-nucleotidase with 100 microM alpha, beta-methyleneadenosine 5'-diphosphate (AOPCP) reduced plasma adenosine to 22 +/- 6 nM. For the determination of adenosine turnover, the decrease in specific radioactivity of added (/sup 3/H)adenosine was measured using a dipyridamole-containing stopping solution. Without altering basal adenosine levels, the half-life was estimated to be 0.6 s. Similar experiments were carried out with washed erythrocytes or in the presence of AOPCP, yielding half-lives of 0.7 and 0.9 s, respectively. When the initial adenosine concentration was 1 microM, its specific activity decreased by only 11% within 5 s, whereas total plasma adenosine exponentially decreased with a half-life of 1.5 s. Venous plasma concentrations were measured after relief of a 3-min forearm ischemia. Changes in plasma adenosine did not correlate well with changes in blood flow but were augmented in the presence of dipyridamole.

Moeser, G.H.S.; Schrader, J.; Deussen, A.

1989-04-01

117

Compartmentation of cardiac adenine nucleotides and formation of adenosine  

Microsoft Academic Search

After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either14C-adenine or14C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3'5'-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady

Jürgen Schrader; Eckehart Gerlach

1976-01-01

118

Evidence for Adenosine\\/Dopamine Receptor Interactions: Indications for Heteromerization  

Microsoft Academic Search

Evidence has been obtained for adenosine\\/dopamine interactions in the central nervous system. There exists an anatomical basis for the existence of functional interactions between adenosine A1R and dopamine D1R and between adenosine A2A and dopamine D2 receptors in the same neurons. Selective A1R agonists affect negatively the high affinity binding of D1 receptors. Activation of A2A receptors leads to a

Rafael Franco; Sergi Ferre; Luigi Agnati; Maria Torvinen; Silvia Gines; Joelle Hillion; Vicent Casado; Pierre-Marie Lledo; Michele Zoli; Carmen Lluis; Kjell Fuxe

2000-01-01

119

Adenosine receptors in regulation of dendritic cell differentiation and function  

PubMed Central

Differentiation of functional dendritic cells (DCs) critically depends on the microenvironment. DCs differentiate in hypoxic tumor sites and inflamed or damaged tissue. Because local concentrations of adenosine reach high physiologically relevant levels in these conditions, we assessed the expression of adenosine receptors and the effect of their activation on differentiation of human monocytes and mouse peritoneal macrophages and hematopoietic progenitor cells (HPCs) into myeloid DCs. Stimulation of adenosine receptors skews DC differentiation toward a distinct cell population characterized by expression of both DC and monocyte/macrophage cell surface markers. Pharmacologic analysis and experiments with cells from A2B adenosine receptor knockout mice identified A2B receptor as the mediator of adenosine effects on DCs. Unlike normal myeloid DCs, adenosine-differentiated DCs have impaired allostimulatory activity and express high levels of angiogenic, pro-inflammatory, immune suppressor, and tolerogenic factors, including VEGF, IL-8, IL-6, IL-10, COX-2, TGF-?, and IDO. They promoted tumor growth if injected into tumors implanted in mice. Using adenosine desaminase knockout animals, we showed that DCs with proangiogenic phenotype are highly abundant under conditions associated with elevated levels of extracellular adenosine in vivo. Adenosine signaling through A2B receptor is an important factor of aberrant DC differentiation and generation of tolerogenic, angiogenic, and proinflammatory cells. PMID:18559975

Novitskiy, Sergey V.; Ryzhov, Sergey; Zaynagetdinov, Rinat; Goldstein, Anna E.; Huang, Yuhui; Tikhomirov, Oleg Y.; Blackburn, Michael R.; Biaggioni, Italo; Carbone, David P.; Feoktistov, Igor

2008-01-01

120

Adenosine-A3 receptors in neutrophil microdomains promotetheformationofbacteria-tetheringcytonemes  

E-print Network

Adenosine-A3 receptors in neutrophil microdomains promotetheformationofbacteria of Pharmacy, University of Nottingham, Nottingham, UK The A3-adenosine receptor (A3AR) has recently emerged as a potential target for modulating their function. Keywords: neutrophils; adenosine receptors; host

Nizet, Victor

121

Edinburgh Research Explorer Adenosine receptor expression and function in rat striatal  

E-print Network

Edinburgh Research Explorer Adenosine receptor expression and function in rat striatal cholinergic & Richardson, PJ 2000, 'Adenosine receptor expression and function in rat striatal cholinergic interneurons immediately and investigate your claim. Download date: 21. Jun. 2014 #12;Adenosine receptor expression

MacDonald, Andrew

122

A study of the role of calcium and magnesium in casein micellar structure in human milk  

E-print Network

. , Texas ASM University; M. S. , Texas ASM University Chair of Advisory Committee: Dr. C. W. Dill The effects of EDTA, phosphatase hydrolysis, calcium chloride, and magnesium chloride on human casein micelles were observed using electron microscopy.... An increasing concentration of EDTA in the casein system dispersed more casein material, Phosphatase hydrolysis dispersed casein micellar material to a greater extent than the EDTA treatments alone. Calcium chloride reaggregated dispersed casein material...

Gallaway, Sheila Ann

2012-06-07

123

Effects of calcium and magnesium hardness on acute copper toxicity to juvenile channel catfish, Ictalurus punctatus  

Microsoft Academic Search

Two experiments were conducted to evaluate the effects of calcium or magnesium hardness on the acute toxicity of copper sulfate to juvenile channel catfish (Ictalurus punctatus) in low alkalinity environments. A preliminary bioassay determined the 48-h LC50 of copper sulfate to be 1.25 mg l?1 for juvenile catfish placed in water with calcium hardness and total alkalinity set at 20

Peter W. Perschbacher; William A. Wurts

1999-01-01

124

An examination of the relationship between calcium and magnesium and hypertension  

E-print Network

For females) +0. 10, had higher blood pressure than those who consumed the suggested ratio. The calcium/magnesium ratio in the er ythrocytes related to systolic blood pressure, and the ratio in mononucleated blood cells was positively correlated... calc1um/magnesium ratio. 16. Calcium, magnesium, and calcium/magnesium ratio oF mononucleated blood cells. . . . . . . . 47 17. Calcium, magnesium, and calcium/magnesium ratio of erythrocytes 47 18. Calcium, magnesium, and calcium/magnesium ratio...

Georghiades, Mary Elizabeth

2012-06-07

125

Decadal changes in potassium, calcium, and magnesium in a deciduous forest soil  

SciTech Connect

Decadal changes in soil exchangeable K{sup +}, Ca{sup 2+}, and Mg{sup 2+} concentrations and contents from 1972 to 2004 in eight intensively monitored plots on Walker Branch Watershed were compared with estimates of increments or decrements in vegetation and detritus. The results from these eight plots compared favorably with those from a more extensive set from 24 soil sampling plots sampled in 1972 and 2004. Increases in exchangeable K{sup +} were noted between 1972 and 1982, but few changes were noted between 1982 and 2004 despite significant increments in vegetation and detritus and significant potential losses by leaching. Total K contents of soils in the 0- to 60-cm sampling depth were very large and a slight amount of weathering could have replenished the K{sup +} lost from exchanges sites. With one notable exception, exchangeable Ca{sup 2+} and Mg{sup 2+} concentrations and contents decreased continuously during the sampling period. Decreases in exchangeable Ca{sup 2+} could be attributed mostly to increments in biomass and detritus, whereas decreases in exchangeable Mg{sup 2+} could not and were attributed to leaching. The major exception to these patterns was in the case of exchangeable Ca{sup 2+}, where significant increases were noted in one plot and attributed to Ca release from the decomposition of Ca-rich coarse woody debris from oak (Quercus spp.) mortality. With minor exceptions, soils and changes in soils among the eight intensively sampled core plots were similar to those in a more extensive set of plots distributed across the watershed. This study shows that averaging among plots can mask significant and important spatial patterns in soil change that must be taken into account in assessing long-term trends.

Mulholland, Patrick J [ORNL; Johnson, Dale W. [University of Nevada, Reno; Todd Jr, Donald E [ORNL; Trettin, Carl [USDA Forest Service

2008-01-01

126

Renal calcium and magnesium excretion during vasopressin administration into sheep with acid or alkaline urine.  

PubMed Central

1. The proposition that changes in renal calcium excretion during vasopressin administration are positively correlated with concurrent changes in urine hydrogen ion concentration was tested by administration of vasopressin into twelve conscious diuresing sheep receiving either alkalinizing or acidifying infusions. 2. Vasopressin-induced antidiuresis in sheep with alkaline urine was associated with significant increases in urinary pH and decreases in the rate of calcium excretion whereas antidiuresis in sheep with acid urine was associated with significant decreases in urinary pH and no consistent effect on calcium excretion. 3. Magnesium excretion increased during vasopressin administration in most experiments regardless of urinary pH changes. 4. Vasopressin administration did not significantly alter the rate of excretion of sodium, potassium, chloride and phosphate or the rates of sodium, potassium, chloride, inulin, para-aminohippurate and osmolal clearance in sheep with either acid or alkaline urine. Potassium excretion and clearance in sheep with alkaline ruine was higher than that of sheep with acid urine during vasopressin infusion. 5. The results support the hypothesis that changes in renal tubular hydrogen ion concentration or bicarbonate concentration caused by water reabsorption from the collecting duct and possibly the late distal tubule could be part of the explanation for changes in renal calcium excretion which occur during vasopressin-induced antidiuresis. PMID:41939

Beal, A M

1979-01-01

127

Factors affecting ex-situ aqueous mineral carbonation using calcium and magnesium silicate minerals  

SciTech Connect

Carbonation of magnesium- and calcium-silicate minerals to form their respective carbonates is one method to sequester carbon dioxide. Process development studies have identified reactor design as a key component affecting both the capital and operating costs of ex-situ mineral sequestration. Results from mineral carbonation studies conducted in a batch autoclave were utilized to design and construct a unique continuous pipe reactor with 100% recycle (flow-loop reactor). Results from the flow-loop reactor are consistent with batch autoclave tests, and are being used to derive engineering data necessary to design a bench-scale continuous pipeline reactor.

Gerdemann, Stephen J.; Dahlin, David C.; O'Connor, William K.; Penner, Larry R.; Rush, G.E.

2004-01-01

128

Incubation of silver catfish, Rhamdia quelen (Pimelodidae), eggs at different calcium and magnesium concentrations  

Microsoft Academic Search

Ca2+ and Mg2+ are important for ionic regulation of freshwater fish because both ions influence the permeability of biological membranes, preventing diffusive flow and high ionic loss to water. The objective of this study was to analyze the hatchery rate and post-hatch survival of silver catfish (Rhamdia quelen) eggs at different Ca2+ and Mg2+ concentrations. Eggs were incubated in continuously

L. V. F Silva; J. I Golombieski; B Baldisserotto

2003-01-01

129

Relative importance of calcium and magnesium in hardness-based modification of copper toxicity  

SciTech Connect

Because of the relationship between water hardness and the toxicity of many metals, total hardness is used as a model parameter to calculate ambient water quality criteria for copper and other metals. However, the relative contribution of the Ca and Mg components of total hardness as modifiers of metals toxicity is not considered in the water quality criteria. Acute Cu toxicity was measured in rainbow trout (Oncorhynchus mykiss) and chinook salmon (O. tshawytscha) swim-up fry in laboratory waters that were formulated to have similar total hardness and alkalinity but different Ca and Mg concentrations. Experiments were performed at nominal total hardness values of 40 and 90 mg/L (as CaCO{sub 3}). In four paired toxicity tests, acute Cu toxicity was significantly lower, i.e., 96-h LC50s were higher, in laboratory waters containing proportionately more Ca (Ca:Mg molar ratios of 1.5--5.2) than in waters containing less Ca (Ca:Mg molar ratios of 0.2--0.8). the relative increase in the 96-h Cu LC50 at higher Ca concentrations, but similar total hardness concentrations, was between 29 and 86% when the low Ca treatment was similar to American Society for Testing and Materials laboratory water. Failure to account for differences in Ca when matching or adjusting for total hardness thus exerts an important influence on the prediction of metal toxicity. These differences must be addressed in water-effect ratio testing in which paired tests with laboratory and site waters are conducted.

Welsh, P.G.; Lipton, J.; Chapman, G.A.; Podrabsky, T.L.

2000-06-01

130

Spatial variability of plant analysis calcium and magnesium levels before and after liming  

Microsoft Academic Search

Plant samples were taken in an 82.5 ft grid at an early and late sampling date in both 1991 and 1992 from a forty acre field in Illinois. Calcium (Ca) and magnesium (Mg) were analyzed on each sample and maps were made showing the levels of each nutrient within the field. Soil pH measurements were also made from each of

David W. Franzen; Ted R. Peck

1995-01-01

131

Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease  

Microsoft Academic Search

Adenosine administration by inhalation elicits concentration-related bronchoconstriction in subjects with asthma and chronic obstructive pulmonary disease (COPD). The mechanisms of adenosine-induced bronchoconstriction appear to involve a selective interaction with activated mast cells with subsequent release of preformed and newly-formed mediators. Further evidence linking adenosine signalling to asthma and COPD comes from the finding that many cell types that play important

R. Polosa

2002-01-01

132

Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo  

Microsoft Academic Search

ObjectiveIntravenous adenosine induces temporary bradycardia. This is due to the activation of extracellular adenosine receptors (ARs). While adenosine can signal through any of four ARs (A1AR, A2AAR, A2BAR, A3AR), previous ex vivo studies implicated the A1AR in the heart-rate slowing effects. Here, we used comparative genetic in vivo studies to address the contribution of individual ARs to the heart-rate slowing

Michael Koeppen; Tobias Eckle; Holger K. Eltzschig; Arnold Schwartz

2009-01-01

133

Adenosine A 1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue — Interactions with insulin  

Microsoft Academic Search

Adenosine acting at adenosine A1 receptors is considered to be one major regulator of adipose tissue physiology. We have examined the role of adenosine and its interactions with insulin in adipose tissue by using A1R knock out (?\\/?) mice. Removal of endogenous adenosine with adenosine deaminase caused lipolysis in A1R (+\\/+), but not A1R (?\\/?) adipocytes. The adenosine analogue, 2-chloroadenosine,

Stina M. Johansson; Eva Lindgren; Jiang-Ning Yang; Andreas W. Herling; Bertil B. Fredholm

2008-01-01

134

Characterization of adenosine binding proteins in human placental membranes  

SciTech Connect

We have characterized two adenosine binding proteins in human placenta. In membranes, one site is detected with ({sup 3}H) -N-ethylcarboxamidoadenosine (({sup 3}H)NECA). This site is similar to the adenosine A{sub 2} receptor. We call this site the adenosine A{sub 2}-like binding site. In detergent extracts, the second site is detected and has the characteristics of an adenosine A{sub 1} receptor. The soluble adenosine A{sub 2}-like binding site cannot be detected without a rapid assay. Binding to the adenosine A{sub 1} receptor with ({sup 3}H)-2-chloroadenosine and ({sup 3}H)NECA is time dependent, saturable, and reversible. Equilibrium displacement analysis with adenosine agonists reveals an A{sub 1} specificity: 2-chloroadenosine > R-phenylisopropyladenosine > 5{prime}-N-ethylcarboxamidoadenosine. The antagonist potency order is 1,3-diethyl-8-phenylxanthine > isobutylmethylxanthine > theophylline. Competition analysis of membranes with the A,-selective ligands ({sup 3}H)-cyclohexyladenosine ({sup 3}H) cylopentylxanthine revealed adenosine A{sub 1} agonist and antagonist potency orders. We have purified the adenosine A{sub 2}-like binding site. The adenosine A{sub 2}-like binding site is an ubiquitous major cellular protein. It is glycosylated, highly asymmetric, and acidic. The native protein is an homodimer with a subunit molecular mass of 98 kDa. The sedimentation coefficient and partial specific volume of the binding complex are 6.9 s and 0.698 ml/g, respectively. The Stokes' radius is 70 {Angstrom}. The native molecular mass of the detergent-protein complex is 230 kDa. The adenosine A{sub 2}-like binding site has an agonist potency order of 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine >> R-phenylisopropyladenosine and an antagonist potency order of isobutylmethylxanthine > theophylline >> 1,3-diethyl-8-phenylxanthine.

Hutchison, K.A.

1989-01-01

135

Physical and functional interaction of A2B adenosine receptor with alpha-actinin-1.  

E-print Network

??Extracellular adenosine is a ubiquitous signaling molecule that modulates many physiological processes. Its actions are mediated by interaction with four subtypes of adenosine receptors, A1,… (more)

Sun, Fengqiang

2009-01-01

136

Electroacupuncture improves neuropathic pain: Adenosine, adenosine 5'-triphosphate disodium and their receptors perhaps change simultaneously?  

PubMed Central

Applying a stimulating current to acupoints through acupuncture needles – known as electroacupuncture – has the potential to produce analgesic effects in human subjects and experimental animals. When acupuncture was applied in a rat model, adenosine 5’-triphosphate disodium in the extracellular space was broken down into adenosine, which in turn inhibited pain transmission by means of an adenosine A1 receptor-dependent process. Direct injection of an adenosine A1 receptor agonist enhanced the analgesic effect of acupuncture. The analgesic effect of acupuncture appears to be mediated by activation of A1 receptors located on ascending nerves. In neuropathic pain, there is upregulation of P2X purinoceptor 3 (P2X3) receptor expression in dorsal root ganglion neurons. Conversely, the onset of mechanical hyperalgesia was diminished and established hyperalgesia was significantly reversed when P2X3 receptor expression was downregulated. The pathways upon which electroacupuncture appear to act are interwoven with pain pathways, and electroacupuncture stimuli converge with impulses originating from painful areas. Electroacupuncture may act via purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on neuropathic pain. PMID:25368638

Ren, Wen; Tu, Wenzhan; Jiang, Songhe; Cheng, Ruidong; Du, Yaping

2012-01-01

137

Engineering embryonic stem cell derived glia for adenosine delivery  

Microsoft Academic Search

Based on the anticonvulsant and neuroprotective properties of adenosine, and based on the long-term survival potential of stem cell derived brain implants, adenosine releasing stem cells may constitute a novel tool for the treatment of epilepsy. Pluripotency and unlimited self-renewal make embryonic stem (ES) cells a particularly versatile donor source for cell transplantation. With the aim to test the feasibility

Denise E. Fedele; Peter Koch; Louis Scheurer; Elizabeth M. Simpson; Hanns Möhler; Oliver Brüstle; Detlev Boison

2004-01-01

138

Adenosine A1 receptor antagonists in clinical research and development  

Microsoft Academic Search

Selective adenosine A1 receptor antagonists targeting renal microcirculation are novel pharmacologic agents that are currently under development for the treatment of acute heart failure as well as for chronic heart failure. Despite several studies showing improvement of renal function and\\/or increased diuresis with adenosine A1 antagonists, particularly in chronic heart failure, these findings were not confirmed in a large phase

Berthold Hocher

2010-01-01

139

A Role for Adenosine Deaminase in Drosophila Larval Development  

PubMed Central

Adenosine deaminase (ADA) is an enzyme present in all organisms that catalyzes the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine. Both adenosine and deoxyadenosine are biologically active purines that can have a deep impact on cellular physiology; notably, ADA deficiency in humans causes severe combined immunodeficiency. We have established a Drosophila model to study the effects of altered adenosine levels in vivo by genetic elimination of adenosine deaminase-related growth factor-A (ADGF-A), which has ADA activity and is expressed in the gut and hematopoietic organ. Here we show that the hemocytes (blood cells) are the main regulator of adenosine in the Drosophila larva, as was speculated previously for mammals. The elevated level of adenosine in the hemolymph due to lack of ADGF-A leads to apparently inconsistent phenotypic effects: precocious metamorphic changes including differentiation of macrophage-like cells and fat body disintegration on one hand, and delay of development with block of pupariation on the other. The block of pupariation appears to involve signaling through the adenosine receptor (AdoR), but fat body disintegration, which is promoted by action of the hemocytes, seems to be independent of the AdoR. The existence of such an independent mechanism has also been suggested in mammals. PMID:15907156

2005-01-01

140

Effect of theophylline on adenosine production in the canine myocardium  

SciTech Connect

Adenosine is thought to participate in local regulation of coronary blood flow. However, competitive antagonists of adenosine fail to block myocardial active hyperemia. The authors examined the effect of locally administered theophylline on active hyperemia and myocardial adenosine production during intracoronary isoproterenol infusion in the dog heart. Isoproterenol decreased coronary resistance and increased myocardial adenosine production. Infusion of theophylline at a rate that attenuated the vasodilator response to exogenously administered adenosine failed to attenuate the increase in coronary blood flow produced by isoproterenol. However, theophylline plus isoproterenol production greater increases in myocardial adensine production than isoproterenol alone. The curves relating resistance and adenosine in the presence of theophylline fell to the right of those in the absence of theophylline. These findings suggest that the failure of theophylline to attenuate isoproterenol hyperemia in the dog heart results at least in part from an increase in adenosine concentration at the arteriole to a level beyond that blocked by this competitive antagonist and that adenosine may in fact play a role in isoproterenol-induced active hyperemia.

McKenzie, J.E.; Steffen, R.P.; Haddy, F.J.

1987-01-01

141

Isolation, characterization and immunological properties of bovine liver adenosine kinase  

SciTech Connect

Adenosine kinase catalyzes the transfer of phosphate from nucleoside triphosphates to adenosine. It also is important in the phosphorylation of adenosine analogs active as anti-cancer and anti-viral drugs. Adenosine kinase from bovine liver was purified by sequential chromatography on DEAE-Sephacel, hydroxylapatite, Ultrogel AcA54, octyl Sepharose, and heptylamine-Sepharose. It exhibited one major band (approx.40 kDa) by sodium dodecylsulfate-polyacrylamide gel electrophoresis and a single peak of similar size by gel permeation chromatography. (/sup 35/S) GTP..gamma..S binding was stimulated in the presence of Mg/sup 2 +/ and adenosine. The K/sub m/ for adenosine was 2.6 ..mu..M. Antibodies raised in rabbits to adenosine kinase, after purification on Protein A-and adenosine kinase-Sepharose, were used to screen several bovine tissues. A 40 kDa immunoreactive protein was most abundant in liver, but was also detected in heart; it was found predominantly in soluble fractions. Antibodies did not significantly cross-react with other guanyl nucleotide-binding proteins.

Noda, M.; Kunz, B.C.; Tsai, S.C.; Adamik, R.; Murtagh, J.J.; Chen, H.C.; Moss, J.; Vaughan, M.

1987-05-01

142

Norepinephrines effect on adenosine transport in the proximal straight tubule  

SciTech Connect

The effect of norepinephrine on C/sup 14/-adenosine transport in the rabbit proximal tubule (S/sub 2/) was studied. The transepithelial transport of adenosine (0.02 mM0 from lumin to bathing solution was measured by its rate of appearance (J/sub A/) in the bathing solution and by its disappearances (J/sub D/) from the luminal fluid. Norepinephrine (0.24 ..mu..M) was added to the bathing solution after a control flux period. After three samples from the experiment period the tubules were quickly harvested and the cellular concentration of C/sup 14/-adenosine was determined. The high cellular adenosine concentration and th marked difference in adenosine appearance rate in the bathing solution compared to the luminal disappearance rate indicates the absorbed adenosine is trapped in the cells. This trapping may be due to adenosine metabolism or difficulty of crossing the basolateral membrane. Whichever is the case, norepinephrine appears to stimulate movement of adenosine or its metabolites into the bathing solution across the basolateral membrane.

Barfuss, D.W.; McCann, W.P.; Katholi, R.E.

1986-03-01

143

Adenosine receptor signaling in the brain immune system  

Microsoft Academic Search

The brain immune system, which consists mainly of astrocytes, microglia and infiltrating immune cells, is quiescent normally, but it is activated in response to pathophysiological events such as ischemia, trauma, inflammation and infection. Adenosine is an endo- genous purine nucleoside that is generated at sites that are subjected to these 'stressful' conditions. Adenosine interacts with specific G-protein-coupled receptors on astrocytes,

György Haskó; Pál Pacher; E. Sylvester Vizi; Peter Illes

2005-01-01

144

Adenosine enhances the relaxing influence of retinal tissue  

Microsoft Academic Search

Retinal tissue from different species continuously releases an as yet unidentified retinal relaxing factor (RRF) lowering tone of isolated arteries. The potential influence of adenosine on this relaxing influence was investigated using isometric tension recording of different isolated arteries. The presence of bovine retinal tissue or rat retinal tissue enhanced the vasorelaxing effect of adenosine on isolated bovine retinal artery.

Nele Maenhaut; Koen Boussery; Christophe Delaey; Johan Van de Voorde

2009-01-01

145

Adenosine A3 receptor stimulation and cerebral ischemia  

PubMed Central

Chronic treatment with the selective adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5’-N-methylcarboxamide (IB-MECA) administered prior to either 10 or 20 min forebrain ischemia in gerbils resulted in improved postischemic cerebral blood circulation, survival, and neuronal preservation. Opposite effects, i.e., impaired postischemic blood flow, enhanced mortality, and extensive neuronal destruction in the hippocampus were seen when IB-MECA was given acutely. Neither adenosine A1 nor A2 receptors are involved in these actions. The data indicate that stimulation of adenosine A3 receptors may play an important role in the development of ischemic damage, and that adenosine A3 receptors may offer a new target for therapeutic interventions. PMID:7821362

Von Lubitz, Dag K.J.E.; Lin, Rick C.-S.; Popik, Piotr; Carter, Margaret F.; Jacobson, Kenneth A.

2012-01-01

146

A High-Affinity Adenosine Kinase from Anopheles Gambiae  

SciTech Connect

Genome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (K{sub m} = 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site, but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with a bound bisubstrate analogue Ap{sub 4}A (2.0 {angstrom} resolution) reveals interactions for adenosine and ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg{sup 2+} ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layer {alpha}/{beta}/{alpha} sandwich, and a small cap domain in contact with adenosine. The specificity and tight binding for adenosine arise from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168, and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64, and Asn68 and the ribosyl 2'- and 3'-hydroxyl groups. The structure is more similar to that of human adenosine kinase (48% identical) than to that of AK from Toxoplasma gondii (31% identical). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to AMP at near the diffusion limit, suggesting an important role for this enzyme in the maintenance of the adenine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects.

M Cassera; M Ho; E Merino; E Burgos; A Rinaldo-Matthis; S Almo; V Schramm

2011-12-31

147

THE OCCURRENCE OF DISSOLVED AND PARTICUI,ATE ADENOSINE.s I -TRIPHOSPHATE IN ANTARCTIC COASTAL ECOSYSTEMS  

E-print Network

THE OCCURRENCE OF DISSOLVED AND PARTICUI,ATE ADENOSINE.s I -TRIPHOSPHATE IN ANTARCTIC COASTAL. A method was developed with a detection l-imit of 4 ng D-ATP. The Antarctic Peninsula coastal marine ecosystem was the fiel-d site. This ecosystem represents a complex physical environment, ranging from

Luther, Douglas S.

148

Adenosine A 2 receptor mediation of pre- and postsynaptic excitatory effects of adenosine in rat hippocampus in vitro  

Microsoft Academic Search

Excitatory effects of adenosine in the rat hippocampus were studied by intracellular recording from CA1 pyramidal cells in vitro. Application of 100 ?M adenosine induced a rapid hyperpolarization and a decrease in input resistance, and depressed the excitatory postsynaptic potentials (EPSPs) evoked by stimulation of Schaffer collaterals in all neurons tested. In 55% of the neurons this was followed by

He Li; James L Henry

1998-01-01

149

Chaperoning of the A1-adenosine receptor by endogenous adenosine-an extension of the retaliatory metabolite concept.  

PubMed

Cell-permeable orthosteric ligands can assist folding of G protein-coupled receptors in the endoplasmic reticulum (ER); this pharmacochaperoning translates into increased cell surface levels of receptors. Here we used a folding-defective mutant of human A1-adenosine receptor as a sensor to explore whether endogenously produced adenosine can exert a chaperoning effect. This A1-receptor-Y(288)A was retained in the ER of stably transfected human embryonic kidney 293 cells but rapidly reached the plasma membrane in cells incubated with an A1 antagonist. This was phenocopied by raising intracellular adenosine levels with a combination of inhibitors of adenosine kinase, adenosine deaminase, and the equilibrative nucleoside transporter: mature receptors with complex glycosylation accumulated at the cell surface and bound to an A1-selective antagonist with an affinity indistinguishable from the wild-type A1 receptor. The effect of the inhibitor combination was specific, because it did not result in enhanced surface levels of two folding-defective human V2-vasopressin receptor mutants, which were susceptible to pharmacochaperoning by their cognate antagonist. Raising cellular adenosine levels by subjecting cells to hypoxia (5% O2) reproduced chaperoning by the inhibitor combination and enhanced surface expression of A1-receptor-Y(288)A within 1 hour. These findings were recapitulated for the wild-type A1 receptor. Taken together, our observations document that endogenously formed adenosine can chaperone its cognate A1 receptor. This results in a positive feedback loop that has implications for the retaliatory metabolite concept of adenosine action: if chaperoning by intracellular adenosine results in elevated cell surface levels of A1 receptors, these cells will be more susceptible to extracellular adenosine and thus more likely to cope with metabolic distress. PMID:25354767

Kusek, Justyna; Yang, Qiong; Witek, Martin; Gruber, Christian W; Nanoff, Christian; Freissmuth, Michael

2015-01-01

150

Adenosine 5'-monophosphate ameliorates D-galactosamine/lipopolysaccharide-induced liver injury through an adenosine receptor-independent mechanism in mice.  

PubMed

D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced lethality and acute liver failure is dependent on endogenously produced inflammatory cytokines. Adenosine has been proven to be a central role in the regulation of inflammatory response. It is not entirely clear that which adenosine action is actually crucial to limiting inflammatory tissue destruction. Here we showed that GalN/LPS challenge elevated hepatic adenosine and induced lethality in adenosine receptor-deficient mice with equal efficiency as wild-type mice. In GalN/LPS-treated mice, pretreatment with adenosine 5'-monophosphate (5'-AMP) significantly elevated hepatic adenosine level and reduced mortality through decreasing cytokine and chemokine production. In RAW264.7 cells, 5'-AMP treatment inhibited the production of inflammatory cytokines, which is not mediated through adenosine receptors. 5'-AMP failed to attenuate LPS-induced nuclear factor-?B (NF-?B) p65 nuclear translocation, but reduced LPS-induced recruitment of NF-?B p65 to inflammatory gene promoters and decreased LPS-induced enrichment of H3K4 dimethylation at the tumor necrosis factor-? (TNF-?) promoter, which was involved in 5'-AMP-induced elevation of cellular adenosine and a decline of methylation potential. In vitro biochemical analysis revealed that adenosine directly attenuated recruitment of NF-?B to the TNF-? and interleukin-6 promoters. Our findings demonstrate that 5'-AMP-inhibiting inflammatory response is not mediated by adenosine receptors and it may represent a potential protective agent for amelioration of LPS-induced liver injury. PMID:24407238

Zhan, Y; Wang, Z; Yang, P; Wang, T; Xia, L; Zhou, M; Wang, Y; Wang, S; Hua, Z; Zhang, J

2014-01-01

151

Double-Stranded RNA Adenosine Deaminases ADAR1 and ADAR2 Have Overlapping Specificities  

E-print Network

Double-Stranded RNA Adenosine Deaminases ADAR1 and ADAR2 Have Overlapping Specificities Katrina A, 2000 ABSTRACT: Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to produce inosines adenosines more efficiently than others. Most of what is known about the intrinsic deamination specificity

Bass, Brenda L.

152

Adenosine deamination in human transcripts generates novel microRNA binding sites  

E-print Network

Adenosine deamination in human transcripts generates novel microRNA binding sites Glen M. Borchert1RNAs), and adenosine-to-inosine (A-to-I) editing, generated by adenosine deaminases that act on double-stranded RNARNA targeting. Here, we analyzed the previously reported adenosine deaminations occur- ring in human c

Bhattacharya, Debashish

153

Adenosine A1 and prostaglandin EP3 receptors mediate global airway contraction following local epithelial injury  

E-print Network

Adenosine A1 and prostaglandin EP3 receptors mediate global airway contraction following local- dependent Ca2+ channel (VGCC)-mediated Ca2+ influx. We found that inhibition of adenosine A1 receptors (or removal of adenosine with adenosine deaminase), cyclooxygenase-2 (COX-2) or EP3 receptors, epidermal

Chen, Zhongping

154

Coronary microembolization does not induce acute preconditioning against infarction in pigs—the role of adenosine  

Microsoft Academic Search

Objective: After coronary microembolization (ME) adenosine is released from ischemic areas of the microembolized myocardium. This adenosine dilates vessels in adjacent nonembolized myocardium and increases coronary blood flow. For ischemic preconditioning (IP) to protect the myocardium against infarction, an increase in the interstitial adenosine concentration (iADO) prior to the subsequent ischemia\\/reperfusion is necessary. We hypothesized that the adenosine release after

Andreas Skyschally; Rainer Schulz; Petra Gres; Ina Konietzka; Claus Martin; Michael Haude; Raimund Erbel; Gerd Heusch

155

Behavioral effects of adenosine analogs in squirrel monkeys: relation to adenosine A 2 receptors  

Microsoft Academic Search

The behavioral effects of seven metabolically stable analogs of adenosine were studied in squirrel monkeys responding under a fixed-interval (FI) schedule of stimulus-shock termination. All drugs produced dose-related decreases in response rate, but differed in potency by up to three orders of magnitude. The 5'-carboxamine and 2-chlorine substituted analogs were more potent than the N6-substituted analogs. The potencies of the

R. D. Spealman; V. L. Coffin

1986-01-01

156

Adenosine receptor antagonists effect on plasma-enhanced killing.  

PubMed

Previous studies demonstrated that naive plasma has inherent capabilities to enhance bacterial opsonization and phagocyte killing, but not all plasma is equally effective. This raised the question of whether plasma constituents other than opsonins may play a role. Adenosine receptor antagonists have been shown to modulate cytokine response and survival in mice after a bacterial challenge. We investigated whether selective adenosine receptor blockade would influence the ability of naive plasma to effectively control bacterial growth. Colonic bacteria- and thioglycollate-elicited peritoneal macrophages and neutrophils were obtained from naive mice. Stock murine plasma from naive was purchased and categorized as having high plasma-enhanced bacterial killing capacity using our previously described methods. Bacteria and plasma were incubated to allow for opsonization and then added to macrophages previously exposed to selected adenosine receptor antagonists: ZM 241385: A2A, MRS1754: A2B, DPCPX: A1, and MRS1220: A3. The final mixture was plated on blood agar plates in aerobic and anaerobic conditions and bacterial colony-forming units quantified after 24 h. This study demonstrated that exogenous adenosine was able to significantly decrease phagocyte killing of cecal bacteria. Blocking adenosine receptors with selective antagonists altered the bacterial killing capacity of plasma. Selectively blocking the A1, A2A, or A2B receptors proved most beneficial at reversing the effect of adenosine. Consistent with previous work, only macrophage killing of bacteria could be modulated by adenosine receptor blockade because neutrophils were unaffected. These data demonstrate that adenosine decreases macrophage killing of enteric bacteria and that this effect is mediated through the adenosine receptors. PMID:24089004

Bauzá, Gustavo; Moitra, Rituparna; Remick, Daniel

2014-01-01

157

Serum adenosine deaminase activity in cutaneous anthrax  

PubMed Central

Background Adenosine deaminase (ADA) activity has been discovered in several inflammatory conditions; however, there are no data associated with cutaneous anthrax. The aim of this study was to investigate serum ADA activity in patients with cutaneous anthrax. Material/Methods Sixteen patients with cutaneous anthrax and 17 healthy controls were enrolled. We measured ADA activity; peripheral blood leukocyte, lymphocyte, neutrophil, and monocyte counts; erythrocyte sedimentation rate; and C reactive protein levels. Results Serum ADA activity was significantly higher in patients with cutaneous anthrax than in the controls (p<0.001). A positive correlation was observed between ADA activity and lymphocyte counts (r=0.589, p=0.021) in the patient group. Conclusions This study suggests that serum ADA could be used as a biochemical marker in cutaneous anthrax. PMID:24997584

Sunnetcioglu, Mahmut; Karadas, Sevdegul; Aslan, Mehmet; Ceylan, Mehmet Resat; Demir, Halit; Oncu, Mehmet Resit; Karahocagil, Mustafa Kas?m; Sunnetcioglu, Aysel; Aypak, Cenk

2014-01-01

158

Insulin and adenosine regulate the phosphatidylcholine concentration in isolated rat adipocyte plasma membranes.  

PubMed

Blockade of adenosine receptors by 3-isobutyl-1-methylxanthine or degradation of endogenous adenosine with adenosine deaminase increased the phosphatidylcholine concentration in isolated rat adipocyte plasma membranes, an effect which was suppressed by the phosphatidylethanolamine methyltransferase inhibitor, S-adenosyl-L-homocysteine, and reversed by the adenosine analogue, N6-(L-phenylisopropyl)-adenosine. For example, the addition of N6-(L-phenylisopropyl)-adenosine to adenosine deaminase pretreated plasma membranes rapidly lowered the concentration of phosphatidylcholine by 171 nmol/mg at 30 seconds compared to control. Insulin-induced stimulation of phospholipid methylation in membranes treated with 3-isobutyl-1-methylxanthine or adenosine deaminase was achieved only after the addition of N6-(L-phenylisopropyl)-adenosine. These results suggest that adenosine receptor occupancy inhibits phospholipid methylation, is required for insulin stimulation of phospholipid methylation, and may perhaps activate a phosphatidylcholine-specific phospholipase C or phospholipase D. PMID:7545381

Kiechle, F L; Sykes, E; Artiss, J D

1995-01-01

159

9-?-L(+) Adenosine: A new naturally occurring plant growth substance elicited by triacontanol in rice  

Microsoft Academic Search

The naturally occurring plant growth substance elicited by triacontanol was found to be 9-ß-L(+) adenosine by physical and spectral methods. At picomolar concentrations, 9-ß-L(+) adenosine stimulated growth as determined by dry weight measurements of several plant species. Reaction of adenosine deaminase with adenosine from rice showed that small quantities of 9-ß-L(+) adenosine exist in plants. We believe this is the

Stanley Ries; Violet Wert; N. F. D. O'Leary; Muraleedharan Nair

1990-01-01

160

Possible mechanism of adenosine protection in carbon tetrachloride acute hepatotoxicity. Role of adenosine by-products and glutathione peroxidase.  

PubMed

Adenosine proved to be an effective hepatoprotector increasing the survival rate of rats receiving lethal doses of CCl4. Searching for the mechanism of action, we found that adenosine transiently prevents the necrotic liver damage associated to an acute CCl4 treatment. The antilipoperoxidative action of the nucleoside was evidenced by a decrease of TBA-reactive products and the diene conjugates elicited by the hepatotoxin. Adenosine's protective effect was demonstrated by reverting the decrease of cytochrome P-450 while preserved intact the activity of the microsomal enzyme glucose-6-phosphatase. CCl4 promoted an increase in the oxidant stress through an enhancement in oxidized glutathione levels. This action was also completely counteracted by the nucleoside. Adenosine was unable to prevent CCl4 activation and, even, increased .CCl3 formation in the presence of PBN in vivo. However, in the presence of the nucleoside, irreversible binding of 14CCl4 to the microsomal lipid fraction of the treated animals was decreased. These results suggest that adenosine protective action might be exerted at the level of the propagation reaction following CCl4 activation. Two possible mechanisms were associated to the nucleoside protection: (1) the peroxide-metabolyzed enzymes, GSH-per, showed a marked increase after 30 minutes of adenosine treatment, which was potentiated by the hepatotoxin, suggesting an important role of this enzyme in the nucleoside's action; (2) the adenosine catabolism induced an increase in uric acid level, and allopurinol, a purine metabolism inhibitor, prevented such elevation as well as the antilipoperoxidative action of adenosine and the increase of GSH-per associated with the nucleoside treatment. These facts strongly suggest that the protective effect elicited by adenosine is not a direct one, but rather is related to its catabolic products, such as uric acid, which has been recognized as a free radical scavenger. PMID:7595931

Chagoya de Sánchez, V; Hernández-Muñoz, R; Yáñez, L; Vidrio, S; Díaz-Muñoz, M

1995-02-01

161

Effects of several 5?-carboxamide derivatives of adenosine on adenosine receptors of human platelets and rat fat cells  

Microsoft Academic Search

The effects of several 5'-carboxamide derivatives of adenosine on stimulatory (Ra) adenosine receptors of human platelets and inhibitory (Ri) adenosine receptors of rat fat cells have been compared. 5'-N-Cyclopropylcarboxamidoadenosine (CPCA) and 5'-N-ethylcarboxamidoadenosine (NECA) most potently inhibited ADP-induced aggregation of human platelets as shown by IC50-values of 0.24 and 0.34 µmol\\/l. 5'-N-Methylcarboxamidoadenosine (MECA; IC50 0.81 µmol\\/l) and 5'-N-carboxamidoadenosine (NCA; IC50 2.1

D. Ukena; E. Böhme; U. Schwabe

1984-01-01

162

Electron Microscopic Localization of Mitochondrial Adenosine Triphosphatase Activity.  

National Technical Information Service (NTIS)

Magnesium-dependent adenosine triphosphatase (ATPase) activity of unfixed, isolated, intact skeletal muscle mitochondria, frozen-thawed mitochondria, and digitonin-disrupted submitochondrial particles was localized ultrastructurally after incubation in a ...

I. W. Grossman, D. H. Heitkamp

1968-01-01

163

Adenosine and the regulation of metabolism and body temperature.  

PubMed

Adenosine levels are increased under conditions of energy deprivation, both because intracellular energy stores are reduced and because ATP is released. The adenosine thus formed can serve to influence energy homeostasis in a number of different ways, besides alterations in blood supply and cellular work (including contraction, maintenance of membrane potential, and biosynthesis), which will be covered in other chapters. Here, effects on energy homeostasis will be briefly reviewed. Adenosine acting at the A(1) receptor is a powerful and nonredundant inhibitor of lipolysis. It increases glucose uptake in fat and muscle, but its effects on insulin secretion may be even more important than the actions at insulin target tissues. Glucagon is also influenced. In addition to these peripheral actions, adenosine acts in the brain to regulate sleep-wakefulness, food intake, and body temperature. These effects are both direct at the relevant neurons and indirect by influences on regulatory transmitters and hormones. PMID:21586356

Fredholm, Bertil B; Johansson, Stina; Wang, Ying-Qing

2011-01-01

164

Structures of adenosine kinase from Trypanosoma brucei brucei.  

PubMed

Trypanosoma brucei is a single-cellular parasite of the genus Kinetoplastida and is the causative agent of African sleeping sickness in humans. Adenosine kinase is a key enzyme in the purine-salvage pathway, phosphorylating adenosine to AMP, and also activates cytotoxic analogues such as cordycepin and Ara-A by their phosphorylation. The structures of T. brucei brucei adenosine kinase (TbAK) in its unliganded open conformation and complexed with adenosine and ADP in the closed conformation are both reported to 2.6?Å resolution. The structures give insight into the binding mode of the substrates and the conformational change induced upon substrate binding. This information can be used to guide the improvement of cytotoxic substrate analogues as potential antitrypanosomal drugs. PMID:24419613

Timm, Jennifer; González-Pacanowska, Dolores; Wilson, Keith S

2014-01-01

165

Attenuating myocardial ischemia by targeting A2B adenosine receptors  

PubMed Central

Due to an imbalance in oxygen supply and demand, myocardial ischemia is associated with profound tissue hypoxia. Studies of hypoxia-elicited adaptive responses during myocardial ischemia revealed a cardioprotective role for the signaling molecule adenosine. In ischemic human hearts, the A2B adenosine receptor (ADORA2B) is selectively induced. Functional studies in genetic models show that Adora2b signaling attenuates myocardial infarction by adapting metabolism towards more oxygen efficient utilization of carbohydrates. This adenosine-mediated cardio-adaptive response involves the transcription factor hypoxia-inducible factor HIF1A and the circadian rhythm protein Per2. In the present review we discuss advances in the current understanding of adenosine-elicited cardioprotection with particular emphasis on ADORA2B, its downstream targets, and their implications on novel strategies to prevent or treat myocardial ischemia. PMID:23540714

Eltzschig, Holger K.; Bonney, Stephanie K.; Eckle, Tobias

2013-01-01

166

21 CFR 864.7040 - Adenosine triphosphate release assay.  

Code of Federal Regulations, 2012 CFR

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7040 Adenosine triphosphate release assay. (a)...

2012-04-01

167

21 CFR 864.7040 - Adenosine triphosphate release assay.  

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7040 Adenosine triphosphate release assay. (a)...

2014-04-01

168

21 CFR 864.7040 - Adenosine triphosphate release assay.  

Code of Federal Regulations, 2010 CFR

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7040 Adenosine triphosphate release assay. (a)...

2010-04-01

169

21 CFR 864.7040 - Adenosine triphosphate release assay.  

Code of Federal Regulations, 2013 CFR

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7040 Adenosine triphosphate release assay. (a)...

2013-04-01

170

Sensing of UO22+ and design of logic gates by the application of supramolecular constructs of ion-dependent DNAzymes.  

PubMed

Supramolecular constructs composed of ion-dependent DNAzymes and their substrates were used to develop DNAzyme cascades that enabled the sensitive detection of UO22+ or the activation of logic gate operations. The supramolecular complex between the UO22+-dependent DNAzyme and its substrate leads, in the presence of UO22+, to the cleavage of the substrate and to the release of the HRP-mimicking DNAzyme that enables the optical analysis of UO22+ (detection limit 1 x 10-9 M). Similarly, supramolecular complexes between the Mg2+- and UO22+-dependent DNAzymes and tailored substrates enables the design of the "OR" and "AND" logic gates, using Mg2+ and UO22+ as inputs. PMID:19199475

Moshe, Michal; Elbaz, Johann; Willner, Itamar

2009-03-01

171

Adenosine enhances the relaxing influence of retinal tissue.  

PubMed

Retinal tissue from different species continuously releases an as yet unidentified retinal relaxing factor (RRF) lowering tone of isolated arteries. The potential influence of adenosine on this relaxing influence was investigated using isometric tension recording of different isolated arteries. The presence of bovine retinal tissue or rat retinal tissue enhanced the vasorelaxing effect of adenosine on isolated bovine retinal artery. In isolated rat carotid artery adenosine elicited no relaxation. However, a small relaxation is observed in the presence of rat retinal tissue, but not in the presence of porcine retina. The fact that adenosine potentiates the effect of rat retinal tissue but not that of a similar piece of porcine retinal tissue indicates species differences. Neither a NO-synthase inhibitor (nitro-L-arginine, 0.1mM), a cyclooxygenase inhibitor (indomethacin, 10 microM) or an epoxygenase inhibitor (miconazole, 10 microM) influenced the enhanced vasodilating effect of adenosine on bovine retinal arteries in the presence of bovine retinal tissue. On the other hand, when the retinal arteries were contracted with 120 mM K(+), adenosine no longer induced relaxation of the preparation with bovine retinal tissue. This is in line with the concept that adenosine enhances the influence of RRF. Also, the fact that rat carotid artery is less sensitive to RRF than bovine retinal artery - corresponding with a less enhanced adenosine response in rat carotid artery - is in line with the potential involvement of the RRF in the enhanced adenosine response. However, experiments using a bioassay setup for RRF gave no evidence for an increased RRF-release from the retina, nor for an increased RRF-sensitivity of the retinal artery in the presence of adenosine. In conclusion, our findings indicate that adenosine potentiates the relaxing influence of bovine and rat retinal tissue. This effect is species dependent as it is not seen with porcine retinal tissue. Neither NO, cyclooxygenase metabolites or epoxyeicosatrienoic acids seem to be involved in this enhanced vasorelaxing response. The involvement of the RRF cannot be excluded. PMID:18992241

Maenhaut, Nele; Boussery, Koen; Delaey, Christophe; Van de Voorde, Johan

2009-01-01

172

Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter  

Microsoft Academic Search

Preliminary screening of a minor, non-xanthine constituent of roasted coffee, 3,4-diferuloyl-1,5-quinolactone (DIFEQ), showed inhibition of the adenosine transporter at low micromolar concentration. DIFEQ is a neutral derivative of the chlorogenic acids, i.e. isomeric mono- and di-substituted coumaroyl-, caffeoyl-, and feruloyl-esters of quinic acid, formed in the roasting process of coffee. Displacement of the adenosine transporter antagonist [3H](S)-(nitrobenzyl)-6-thioinosine binding by DIFEQ

Tomas de Paulis; Dennis E Schmidt; Aleksandra K Bruchey; Michael T Kirby; Michael P McDonald; Patricia Commers; David M Lovinger; Peter R Martin

2002-01-01

173

Adenosine A1 receptor activation inhibits LTP in sympathetic ganglia  

Microsoft Academic Search

The effects of adenosine on long-term potentiation of sympathetic ganglia was studied in the isolated superior cervical ganglion of the rat, using extracellularly recorded compound action potential as an index of synaptic transmission. Adenosine in a small concentration (2 ?M) blocked the post-tetanic potentiation without affecting long-term potentiation. Higher concentrations blocked both responses with no significant effect on basal transmission.

Yvonne H Hogan; Rollin Hawkins; Karim A Alkadhi

1998-01-01

174

Adenosine promotes vascular barrier function in hyperoxic lung injury.  

PubMed

Hyperoxic lung injury is characterized by cellular damage from high oxygen concentrations that lead to an inflammatory response in the lung with cellular infiltration and pulmonary edema. Adenosine is a signaling molecule that is generated extracellularly by CD73 in response to injury. Extracellular adenosine signals through cell surface receptors and has been found to be elevated and plays a protective role in acute injury situations. In particular, ADORA2B activation is protective in acute lung injury. However, little is known about the role of adenosine signaling in hyperoxic lung injury. We hypothesized that hyperoxia-induced lung injury leads to CD73-mediated increases in extracellular adenosine, which is protective through ADORA2B signaling pathways. To test this hypothesis, we exposed C57BL6, CD73(-/-), and Adora2B(-/-) mice to 95% oxygen or room air and examined markers of pulmonary inflammation, edema, and monitored lung histology. Hyperoxic exposure caused pulmonary inflammation and edema in association with elevations in lung adenosine levels. Loss of CD73-mediated extracellular adenosine production exacerbated pulmonary edema without affecting inflammatory cell counts. Furthermore, loss of the ADORA2B had similar results with worsening of pulmonary edema following hyperoxia exposure without affecting inflammatory cell infiltration. This loss of barrier function correlated with a decrease in occludin in pulmonary vasculature in CD73(-/-) and Adora2B(-/-) mice following hyperoxia exposure. These results demonstrate that exposure to a hyperoxic environment causes lung injury associated with an increase in adenosine concentration, and elevated adenosine levels protect vascular barrier function in hyperoxic lung injury through the ADORA2B-dependent regulation of occludin. PMID:25263205

Davies, Jonathan; Karmouty-Quintana, Harry; Le, Thuy T; Chen, Ning-Yuan; Weng, Tingting; Luo, Fayong; Molina, Jose; Moorthy, Bhagavatula; Blackburn, Michael R

2014-09-01

175

Proton transfer in oxidized adenosine self-aggregates  

NASA Astrophysics Data System (ADS)

The UV-vis and the IR spectra of derivativized adenosine in dichloromethane have been recorded during potentiostatic oxidation at an optically transparent thin layer electrode. Oxidized adenosine shows a broad Zundel like absorption extending from 2800 up to 3600 cm-1, indicating that a proton transfer process is occurring. Theoretical computations predict that proton transfer is indeed favored in oxidized 1:1 self-association complexes and allow to assign all the observed transient spectroscopic signals.

Capobianco, Amedeo; Caruso, Tonino; Celentano, Maurizio; La Rocca, Mario Vincenzo; Peluso, Andrea

2013-10-01

176

Coronary Vasoactivity of Adenosine in the Conscious Dog  

Microsoft Academic Search

SUMMARY Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 ± 0.18 (SD) \\/IM and at 1.01 ± 0.25 pM in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique

RAY A. OLSSON; EDWARD M. KHOURI; JULIUS L. BEDYNEK; JOHN MCLEAN

2010-01-01

177

[Sleep-wake regulation by prostaglandin D2 and adenosine].  

PubMed

Prostaglandin (PG) D2 and adenosine are potent endogenous somnogens that accumulate in the brain during prolonged wakefulness. Lipocalin-type PGD synthase (L-PGDS) catalyzes the isomerization of PGH2, a common precursor of various prostanoids, to produce PGD2. L-PGDS is localized in the leptomeninges, choroid plexus, and oligodendrocytes of the central nervous system. PGD2 stimulates DP1 receptors localized in the basal forebrain and increases the local extracellular concentration of adenosine, a paracrine signaling molecule, to promote sleep. Adenosine activates adenosine A2A receptor-expressing neurons in the basal forebrain and ventrolateral preoptic area (VLPO) and inhibits adenosine A1 receptor-possessing arousal neurons. Sleep-promoting neurons in the VLPO send inhibitory signals to suppress the histaminergic neurons in the tuberomammillary nucleus (TMN); the histaminergic neurons contribute to arousal through histamine H1 receptors. GABAergic inhibition of TMN is involved in the induction of non-rapid eye movement (non-REM) sleep by PGD2 and adenosine A2A agonists. The neural network between the VLPO and TMN is considered to play a key role in regulation of vigilance states. Administering an L-PGD inhibitor (SeCl4), DP1 antagonist (ONO-4127Na), or adenosine A2A receptor antagonist (caffeine) suppresses both non-REM and REM sleep, indicating that the PGD2-adenosine system is crucial for maintaining physiological sleep. Selective gene-deletion strategies based on Cre/loxP technology and focal RNA interference have been used for silencing the expression of the A2A receptor by local infection with adeno-associated virus carrying Cre-recombinase or short hairpin RNA. The results of these studies have shown that the A2Asubreceptors in the shell region of the nucleus accumbens are responsible for the effect of caffeine on wakefulness. PMID:22647469

Nagata, Nanae; Urade, Yoshihiro

2012-06-01

178

Doxofylline, an antiasthmatic drug lacking affinity for adenosine receptors.  

PubMed

In the present study the interaction of doxofylline, a new antiasthmatic drug, with A1- and A2-adenosine receptors of the guinea-pig brain and rat striatum was investigated in comparison with known methylxanthine derivatives. Inhibition studies of N6-cyclohexyl-3H-adenosine (3H-CHA), 1,3-diethyl-8-3H-phenylxanthine (3H-DPX) binding and 3H-5'-N-ethylcarboxamidoadenosine (3H-NECA) binding showed how doxofylline did not bind to adenosine receptors in a pharmacological fashion, since doxofylline affinity for A1- and A2-adenosine receptors lies in a 10(-4) M range, a concentration which is too high to have any pharmacological meaning or predictability. However, saturation binding studies demonstrate that doxofylline behaves as a competitive inhibitor of the 3 radioligands used to label adenosine receptors. These data seem to corroborate the theory that antagonism to adenosine receptors is not necessarily associated with bronchodilator activity of methylxanthines, and explain the lack of the typically unwanted side effects induced by methylxanthine derivatives after doxofylline administration. PMID:3245738

Cirillo, R; Barone, D; Franzone, J S

1988-01-01

179

Adenosine deaminase from camel tick Hyalomma dromedarii: purification and characterization.  

PubMed

Adenosine deaminase is involved in purine metabolism and is a key enzyme for the control of the cellular levels of adenosine. Adenosine deaminase activity showed significant changes during embryogenesis of the camel tick Hyalomma dromedarii. From the elution profile of chromatography on DEAE-sepharose, three forms of enzyme (ADAI, ADAII and ADAIII) were separated. ADAII was purified to homogeneity after chromatography on Sephacryl S-200. The molecular mass of adenosine deaminase ADAII was 42 kDa for the native enzyme and represented a monomer of 42 kDa by SDS-PAGE. The enzyme had a pH optimum at 7.5 and temperature optimum at 40 degrees C with heat stability up to 40 degrees C. ADAII had a K (m) of 0.5 mM adenosine with higher affinity toward deoxyadenosine and adenosine than other purines. Ni(2+), Ba(2+), Zn(2+), Li(2+), Hg(2+) and Mg(2+) partially inhibited the ADAII. Mg(2+) was the strongest inhibitor by 91% of the enzyme's activity. PMID:17089216

Mohamed, Tarek M

2006-01-01

180

Myocardial perfusion scintigraphy during maximal coronary artery vasodilation with adenosine  

SciTech Connect

Pharmacologic coronary vasodilation as an adjunct to thallium-201 myocardial perfusion scintigraphy provides an important alternative form of stress that has been increasingly used in patients unable to perform an exercise stress test. Although dipyridamole has traditionally been used for this purpose, there are several compelling reasons why adenosine may be a preferable agent. First, dipyridamole acts by blocking the reuptake and transport of adenosine, which is the effective substance responsible for coronary vasodilation. Second, exogenous adenosine has a very short half-life (less than 2 seconds), which explains its very short duration of action as well as the brief, self-limiting duration of its side effects. Third, the adenosine infusion is controllable and may be increased or decreased as desired. Fourth, the coronary vasodilation induced by the doses of adenosine we recommend (140 micrograms/kg/min) may be more profound than that induced by the standard dipyridamole dose. Our experience to date, with nearly 1,000 patients studied, shows the adenosine thallium-201 test to be practical and well tolerated, with high sensitivity (87%) and specificity (94%) for detecting coronary artery disease.

Verani, M.S.; Mahmarian, J.J. (Baylor College of Medicine, Houston, TX (USA))

1991-05-21

181

Adenosine A2A and A2B receptors are both required for adenosine A1 receptor-mediated cardioprotection  

PubMed Central

All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A2A and/or A2B receptors modulate adenosine A1 receptor-mediated cardioprotection. Isolated perfused hearts of wild-type (WT), A2A knockout (KO), and A2BKO mice, perfused at constant pressure and constant heart rate, underwent 30 min of global ischemia and 60 min of reperfusion. The adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and for the first 10 min of reperfusion. Treatment with CHA significantly improved postischemic left ventricular developed pressure (74 ± 4% vs. 44 ± 4% of preischemic left ventricular developed pressure at 60 min of reperfusion) and reduced infarct size (30 ± 2% with CHA vs. 52 ± 5% in control) in WT hearts, effects that were blocked by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). Treatments with the A2A receptor agonist CGS-21680 (200 nM) and the A2B agonist BAY 60-6583 (200 nM) did not exert any beneficial effects. Deletion of adenosine A2A or A2B receptor subtypes did not alter ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in hearts of mice from either KO group. These findings indicate that both adenosine A2A and A2B receptors are required for adenosine A1 receptor-mediated cardioprotection, implicating a role for interactions among receptor subtypes. PMID:21743001

Zhan, Enbo; McIntosh, Victoria J.

2011-01-01

182

Mechanisms of the Potentiation by Adenosine of Adenosine Triphosphate-Induced Calcium Release in Tracheal Smooth-Muscle Cells  

Microsoft Academic Search

The effects of concomitant P 1 -receptor stimulation on peak intracellular Ca 2 1 release by extracellular adenosine 5 9 -triphosphate (ATP) and 5-hydroxytryptamine (5-HT) were investigated in cultured airway smooth-muscle (ASM) cells. The results show that peak Ca 2 1 release to ATP is enhanced by preincubation with adenosine (ADO) and with the specific A 3 receptor agonist 1-Deoxy-1-(6-{((3-iodophenyl)methyl)

Marie Claire Michoud; Florence C. Tao; Amynah A. Pradhan; James G. Martin

1999-01-01

183

An adenosine nucleoside inhibitor of dengue virus  

PubMed Central

Dengue virus (DENV), a mosquito-borne flavivirus, is a major public health threat. The virus poses risk to 2.5 billion people worldwide and causes 50 to 100 million human infections each year. Neither a vaccine nor an antiviral therapy is currently available for prevention and treatment of DENV infection. Here, we report a previously undescribed adenosine analog, NITD008, that potently inhibits DENV both in vitro and in vivo. In addition to the 4 serotypes of DENV, NITD008 inhibits other flaviviruses, including West Nile virus, yellow fever virus, and Powassan virus. The compound also suppresses hepatitis C virus, but it does not inhibit nonflaviviruses, such as Western equine encephalitis virus and vesicular stomatitis virus. A triphosphate form of NITD008 directly inhibits the RNA-dependent RNA polymerase activity of DENV, indicating that the compound functions as a chain terminator during viral RNA synthesis. NITD008 has good in vivo pharmacokinetic properties and is biologically available through oral administration. Treatment of DENV-infected mice with NITD008 suppressed peak viremia, reduced cytokine elevation, and completely prevented the infected mice from death. No observed adverse effect level (NOAEL) was achieved when rats were orally dosed with NITD008 at 50 mg/kg daily for 1 week. However, NOAEL could not be accomplished when rats and dogs were dosed daily for 2 weeks. Nevertheless, our results have proved the concept that a nucleoside inhibitor could be developed for potential treatment of flavivirus infections. PMID:19918064

Yin, Zheng; Chen, Yen-Liang; Schul, Wouter; Wang, Qing-Yin; Gu, Feng; Duraiswamy, Jeyaraj; Kondreddi, Ravinder Reddy; Niyomrattanakit, Pornwaratt; Lakshminarayana, Suresh B.; Goh, Anne; Xu, Hao Ying; Liu, Wei; Liu, Boping; Lim, Joanne Y. H.; Ng, Chuan Young; Qing, Min; Lim, Chin Chin; Yip, Andy; Wang, Gang; Chan, Wai Ling; Tan, Hui Pen; Lin, Kai; Zhang, Bo; Zou, Gang; Bernard, Kristen A.; Garrett, Christine; Beltz, Karen; Dong, Min; Weaver, Margaret; He, Handan; Pichota, Arkadius; Dartois, Veronique; Keller, Thomas H.; Shi, Pei-Yong

2009-01-01

184

Effect of adenosine on the growth of human T-lymphocyte leukemia cell line MOLT-4.  

PubMed

Adenosine has been observed to suppress the growth of MOLT-4 human leukemia cells in vitro. Changes in the cell cycle, especially increased percentage of cells in S phase, prolonged generation time, and induction of apoptosis at higher adenosine concentrations have been found to be responsible for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake of adenosine, reversed partially but significantly the adenosine-induced growth suppression. It follows from these results that the action of adenosine on the MOLT-4 cells comprises its cellular uptake and intracellular operation. These findings present new data on anticancer efficacy of adenosine. PMID:17882653

Streitová, Denisa; Weiterová, Lenka; Hofer, Michal; Holá, Jirina; Horváth, Viktor; Kozubík, Alois; Znojil, Vladimír

2007-09-01

185

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design  

E-print Network

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase adenosine analogues were identified as low micromolar inhibitors of glyceraldehyde- 3-phosphate, and this facilitated the understanding of the relative affinities of a series of adenosine analogues for the various

Gelb, Michael

186

Engineered adenosine-releasing cells for epilepsy therapy: Human mesenchymal stem cells and human embryonic stem cells  

Microsoft Academic Search

Summary  Adenosine is a modulator of neuronal activity with anticonvulsant and neuroprotective properties. Conversely, focal deficiency\\u000a in adenosine contributes to ictogenesis. Thus, focal reconstitution of adenosine within an epileptogenic brain region constitutes\\u000a a rational therapeutic approach, whereas systemic augmentation of adenosine is precluded by side effects. To meet the therapeutic\\u000a goal of focal adenosine augmentation, genetic disruption of the adenosine metabolizing

Detlev Boison

2009-01-01

187

Biologic implications of extracellular adenosine in hepatic ischemia and reperfusion injury  

PubMed Central

The purine nucleoside adenosine is clinically employed in the treatment of supraventricular tachycardia. In addition, it has direct coronary vasodilatory effects, and may influence platelet aggregation. Experimental observations mechanistically link extracellular adenosine to cellular adaptation to hypoxia. Adenosine generation has been implicated in several pathophysiologic processes including angiogenesis, tumor defenses, and neurodegeneration. In solid organ transplantation, prolonged tissue ischemia and subsequent reperfusion injury may lead to profound graft dysfunction. Importantly, conditions of limited oxygen availability are associated with increased production of extracellular adenosine and subsequent tissue protection. Within the rapidly expanding field of adenosine biology, several enzymatic steps in adenosine production have been characterized and multiple receptor subtypes have been identified. In this review, we briefly examine the biologic steps involved in adenosine generation, and chronicle the current state of adenosine signaling in hepatic ischemia and reperfusion injury. PMID:23924168

Zimmerman, Michael A.; Kam, Igal; Eltzschig, Holger; Grenz, Almut

2013-01-01

188

Investigating real-time activation of adenosine receptors by bioluminescence resonance energy transfer technique  

NASA Astrophysics Data System (ADS)

Adenosine receptors play important roles in many physiological and pathological processes, for example regulating myocardial oxygen consumption and the release of neurotransmitters. The activations of adenosine receptors have been studied by some kinds of techniques, such as western blot, immunohistochemistry, etc. However, these techniques cannot reveal the dynamical response of adenosine receptors under stimulation. In this paper, bioluminescence resonance energy transfer technique was introduced to study the real-time activation of adenosine receptors by monitoring the dynamics of cyclic adenosine monophosphate (cAMP) level. The results showed that there were significant differences between adenosine receptors on real-time responses under stimulation. Moreover, the dynamics of cAMP level demonstrated that competition between adenosine receptors existed. Taken together, our study indicates that monitoring the dynamics of cAMP level using bioluminescence resonance energy transfer technique could be one potential approach to investigate the mechanism of competitions between adenosine receptors.

Huang, Yimei; Yang, Hongqin; Zheng, Liqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen

2013-02-01

189

Therapeutic potential of adenosine receptor antagonists and agonists.  

PubMed

The adenosine receptors (A(1), A(2A), A(2B) and A(3)) are important and ubiquitous mediators of cellular signalling, which play vital roles in protecting tissues and organs from damage. Launched drugs include the adenosine receptor antagonists theophylline and doxofylline (both used as bronchodilators in respiratory disorders such as asthma), while several compounds are presently in clinical trials for a range of indications, including heart failure, Parkinson's disease, rheumatoid arthritis, cancer, pain and chronic obstructive pulmonary disease. A host of companies and institutions are addressing the huge potential for the development of selective adenosine receptor agonists and antagonists, so that it appears we are on the verge of a new wave of compounds approaching the market for many unmet medical needs. This review presents an analysis of the patenting activity in the area for 2006 and an interpretation and reflection on the developments that we can expect in the future. PMID:20144084

Press, Neil J; Gessi, Stefania; Borea, Pier A; Polosa, Riccardo

2007-08-01

190

Correlation of sinus slowing and hyperpolarization caused by adenosine in sinus node  

Microsoft Academic Search

The effect of adenosine on sinus node cells was examined in a preparation that precluded pacemaker shift. It was found that adenosine produced a dose-dependent slowing in rate. In examining the effects on the action potential parameters (n=10), adenosine caused a significant increase in the maximum diastolic potential (control =-62±2 mV, adenosine, 1×10-4 M, =-67±3 mV) and a significant increase

G. Alexander West; Luiz Belardinelli

1985-01-01

191

Recent developments in the field of A 2A and A 3 adenosine receptor antagonists  

Microsoft Academic Search

In the last years adenosine receptors have been extensively studied, and mainly at present we understand the importance of A2A and A3 adenosine receptors. A2A selective adenosine receptors antagonists are promising new drugs for the treatment of Parkinson's disease, while A3 selective adenosine receptors antagonists have been postulated as novel anti-inflammatory and antiallergic agents; recent studies also indicated a possible

Pier Giovanni Baraldi; Mojgan Aghazadeh Tabrizi; Andrea Bovero; Barbara Avitabile; Delia Preti; Francesca Fruttarolo; Romeo Romagnoli; Katia Varani; Pier Andrea Borea

2003-01-01

192

Subclasses of adenosine receptors in the central nervous system: Interaction with caffeine and related methylxanthines  

Microsoft Academic Search

1.The potencies of caffeine and related methylxanthines as adenosine antagonists were assessed with respect to three apparent subtypes of adenosine receptors in rat brain preparations: (i) the A1-adenosine receptor which binds with a very high affinity the ligand [3H]cyclohexyladenosine (KD, 1 nM) in rat brain membranes; (ii) a ubiquitous low-affinity A2-adenosine receptor which activates cyclic AMP accumulation in rat brain

John W. Daly; Pamela Butts-Lamb; William Padgett

1983-01-01

193

The Diagnostic Efficacy of Adenosine Deaminase in Tubercular Effusion  

PubMed Central

Objective This study aims to evaluate the diagnostic efficacy of adenosine deaminase in tubercular effusions. Methods This study was conducted at the Department of General Medicine and Cardiovascular and Thoracic Surgery, SKIMS, for a period of two years between November 2008 and November 2010. A total of 57 patients presenting with pleural effusions during the two-year study period, who presented with clinical manifestations suggestive of tuberculosis (i.e., the presence of productive cough, low-grade fever, night sweats, weight loss, and chest pain, especially if these symptoms last 34 weeks) were included in the study. If the patients presented with less than two of these symptoms, and especially if the clinical manifestations were of <4 weeks duration, they were excluded from the study. Results The mean adenosine deaminase activity level in all the 57 patients was 109 U/L while the mean adenosine deaminase activity levels in pleural TB patients was 80 U/, and 64 U/L in the controls (p=0.381). Considering 40 U/L as the cut off, the results were positive in 35 out of 39 tuberculosis patients and 9 out of 18 controls. The sensitivity of adenosine deaminase for tubercular effusions worked out to be 90%, with only 50% specificity. Conclusion This study suggests that the estimation of adenosine deaminase activity in pleural fluid is a rapid diagnostic tool for differentiation of tubercular and non tubercular-effusions. The sensitivity and specificity of adenosine deaminase for tubercular effusions in this study was 90% and 50% respectively. PMID:24223245

Kelam, Mohd Arif; Ganie, Farooq Ahmad; Shah, Bashir Ahmad; Ganie, Shabir Ahmad; Wani, Mohd Lateef; Wani, Nasir-U-Din; Gani, Masaratul

2013-01-01

194

The guanosine-adenosine interaction exists in vivo.  

PubMed

In cultured renal cells and isolated perfused kidneys, extracellular guanosine augments extracellular adenosine and inosine (the major renal metabolite of adenosine) levels by altering the extracellular disposition of these purines. The present study addressed whether this "guanosine-adenosine mechanism" exists in vivo. In rats (n = 15), intravenous infusions of adenosine (1 µmol/kg per minute) decreased mean arterial blood pressure (MABP) from 114 ± 4 to 83 ± 5 mm Hg, heart rate (HR) from 368 ± 11 to 323 ± 9 beats/min), and renal blood flow (RBF) from 6.2 ± 0.5 to 5.3 ± 0.6 ml/min). In rats (n = 15) pretreated with intravenous guanosine (10 µmol/kg per minute), intravenous adenosine (1 µmol/kg per minute) decreased MABP (from 109 ± 4 to 58 ± 5 mm Hg), HR (from 401 ± 10 to 264 ± 20 beats/min), and RBF (from 6.2 ± 0.7 to 1.7 ± 0.3). Two-factor analysis of variance (2F-ANOVA) revealed a significant interaction (P < 0.0001) between guanosine and adenosine for MABP, HR, and RBF. In control rats, the urinary excretion rate of endogenous inosine was 211 ± 103 ng/30 minutes (n = 9); however, in rats treated with intravenous guanosine (10 µmol/kg per minute), the excretion rate of inosine was 1995 ± 300 ng/30 minutes (n = 12; P < 0.0001 versus controls). Because adenosine inhibits inflammatory cytokine production, we also examined the effects of intravenous guanosine on endotoxemia-induced increases in tumor necrosis factor-? (TNF-?). In control rats (n = 7), lipopolysaccharide (LPS; Escherichia coli 026:B6 endotoxin; 30 mg/kg) increased plasma TNF-? from 164 ± 56 to 4082 ± 730 pg/ml, whereas in rats pretreated with intravenous guanosine (10 µmol/kg per minute; n = 6), LPS increased plasma TNF-? from 121 ± 45 to 1821 ± 413 pg/ml (2F-ANOVA interaction effect, P = 0.0022). We conclude that the guanosine-adenosine mechanism exists in vivo and that guanosine may be a useful therapeutic for reducing inflammation. PMID:25002416

Jackson, Edwin K; Mi, Zaichuan

2014-09-01

195

Extraction and Analysis of Adenosine Phosphate in Cells of Microcystis Aeruginosa  

Microsoft Academic Search

Four methods, perchloric acid extraction, organic solvent extraction, boiling bitter salt solution extraction, and boiling bitter salt solution with ultrasonic extraction, were used for the extraction of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine momophosphate (AMP) from the cells of Microcystis aeruginosa. The method of boiling bitter salt solution with ultrasonic extraction was chosen as the optimum method. The

Dai Rui-Hua; Liu Hui-Juan; Qu Jiu-Hui

2007-01-01

196

Comparative Transcriptome Analysis of Bacillus subtilis Responding to Dissolved Oxygen in Adenosine Fermentation  

Microsoft Academic Search

Dissolved oxygen (DO) is an important factor for adenosine fermentation. Our previous experiments have shown that low oxygen supply in the growth period was optimal for high adenosine yield. Herein, to better understand the link between oxygen supply and adenosine productivity in B. subtilis (ATCC21616), we sought to systematically explore the effect of DO on genetic regulation and metabolism through

Wen-Bang Yu; Shu-Hong Gao; Chun-Yun Yin; Ying Zhou; Bang-Ce Ye

2011-01-01

197

Neuronal transporter and astrocytic ATP exocytosis underlie activity-dependent adenosine release in the hippocampus.  

PubMed

The neuromodulator adenosine plays an important role in many physiological and pathological processes within the mammalian CNS. However, the precise mechanisms of how the concentration of extracellular adenosine increases following neural activity remain contentious. Here we have used microelectrode biosensors to directly measure adenosine release induced by focal stimulation in stratum radiatum of area CA1 in mouse hippocampal slices. Adenosine release was both action potential and Ca²? dependent and could be evoked with low stimulation frequencies and small numbers of stimuli. Adenosine release required the activation of ionotropic glutamate receptors and could be evoked by local application of glutamate receptor agonists. Approximately 40% of stimulated-adenosine release occurred by translocation of adenosine via equilibrative nucleoside transporters (ENTs). This component of release persisted in the presence of the gliotoxin fluoroacetate and thus results from the direct release of adenosine from neurons. A reduction of adenosine release in the presence of NTPDase blockers, in slices from CD73(-/-) and dn-SNARE mice, provides evidence that a component of adenosine release arises from the extracellular metabolism of ATP released from astrocytes. This component of release appeared to have slower kinetics than the direct ENT-mediated release of adenosine. These data suggest that activity-dependent adenosine release is surprisingly complex and, in the hippocampus, arises from at least two distinct mechanisms with different cellular sources. PMID:23713028

Wall, Mark J; Dale, Nicholas

2013-08-15

198

Neuronal transporter and astrocytic ATP exocytosis underlie activity-dependent adenosine release in the hippocampus  

PubMed Central

The neuromodulator adenosine plays an important role in many physiological and pathological processes within the mammalian CNS. However, the precise mechanisms of how the concentration of extracellular adenosine increases following neural activity remain contentious. Here we have used microelectrode biosensors to directly measure adenosine release induced by focal stimulation in stratum radiatum of area CA1 in mouse hippocampal slices. Adenosine release was both action potential and Ca2+ dependent and could be evoked with low stimulation frequencies and small numbers of stimuli. Adenosine release required the activation of ionotropic glutamate receptors and could be evoked by local application of glutamate receptor agonists. Approximately 40% of stimulated-adenosine release occurred by translocation of adenosine via equilibrative nucleoside transporters (ENTs). This component of release persisted in the presence of the gliotoxin fluoroacetate and thus results from the direct release of adenosine from neurons. A reduction of adenosine release in the presence of NTPDase blockers, in slices from CD73?/? and dn-SNARE mice, provides evidence that a component of adenosine release arises from the extracellular metabolism of ATP released from astrocytes. This component of release appeared to have slower kinetics than the direct ENT-mediated release of adenosine. These data suggest that activity-dependent adenosine release is surprisingly complex and, in the hippocampus, arises from at least two distinct mechanisms with different cellular sources. PMID:23713028

Wall, Mark J; Dale, Nicholas

2013-01-01

199

Role of Adenosine on Ventricular Overdrive Suppression in Isolated Guinea Pig Hearts and Purkinje Fibers  

Microsoft Academic Search

SUMMARY. The present study was undertaken to demonstrate and characterize potentiation of ventricular overdrive suppression by adenosine. To substantiate that adenosine has an enhanced effect on overdrive suppression, it would be necessary to demonstrate that adenosine increases pause duration independent of slowing spontaneous pre-drive rate. In isolated perfused guinea pig hearts with surgically induced complete atrioventricular block, the effect of

Robert C. Wesley; Luiz Belardinelli

200

Direct visualization by electron microscopy of the weakly bound intermediates in the actomyosin adenosine triphosphatase cycle  

E-print Network

adenosine triphosphatase cycle Thomas D. Pollard, * Dhansukhlal Bhandari, * Pamela Maupin,* Daniel the transient intermediates in the actin-myosin adenosine triphosphatase (ATPase) cycle for direct observation by electron microscopy. We focused on the low affinity complexes of myosin- adenosine triphosphate (ATP

201

Arterial Spin Labeled MRI Detects Increase in Myocardial Blood Flow with Adenosine , P. Varadarajan2  

E-print Network

Arterial Spin Labeled MRI Detects Increase in Myocardial Blood Flow with Adenosine Z. Zun1 , P applied myocardial ASL to the measurement of MBF at rest and during an infusion of adenosine, which-pass perfusion imaging with adenosine. All experiments were performed on a GE Signa 3.0 T EXCITE HDx system

Southern California, University of

202

Edinburgh Research Explorer Tissue distribution of adenosine receptor mRNAs in the rat  

E-print Network

Edinburgh Research Explorer Tissue distribution of adenosine receptor mRNAs in the rat Citation distribution of adenosine receptor mRNAs in the rat' British Journal of Pharmacology, vol 118, no. 6, pp. 1461 distribution of adenosine receptor mRNAs in the rat *tAlistair K. Dixon, *tAmelie K. Gubitz, tDalip J

MacDonald, Andrew

203

Role of adenosine in the hypoxia-induced hypothermia of toads  

E-print Network

Role of adenosine in the hypoxia-induced hypothermia of toads LUIZ G. S. BRANCO,1 ALEXANDRE A, Glenn J. Tattersall, and Stephen C. Wood. Role of adenosine in the hypoxia-induced hypothermia of toads remain unclear. We tested the hypothesis that adenosine mediates hypoxia-induced hypothermia in toads

Tattersall, Glenn

204

Adenosine A3 receptor stimulation induces protection of skeletal muscle from eccentric exercise-mediated injury  

E-print Network

Adenosine A3 receptor stimulation induces protection of skeletal muscle from eccentric exercise, Zambraski EJ, Rader EP, Campbell KP, Liang BT. Adenosine A3 receptor stimulation induces protection of this study was to determine whether adenosine receptor stimulation can mediate protection from eccentric

Campbell, Kevin P.

205

Synthesis of adenosine derivatives as transcription initiators and preparation of 5 fluorescein-and  

E-print Network

METHOD Synthesis of adenosine derivatives as transcription initiators and preparation of 5, Hattiesburg, Mississippi 39406-5043, USA ABSTRACT Expanding our previous finding of an adenosine-initiated transcription system, we now demonstrate that either the 5 site or the N6 site of adenosine nucleotides can

Huang, Faqing

206

Adenosine deaminase-related growth factors stimulate cell proliferation in Drosophila  

E-print Network

Adenosine deaminase-related growth factors stimulate cell proliferation in Drosophila by depleting extracellular adenosine Michal Zurovec* , Tomas Dolezal* , Michal Gazi* , Eva Pavlova* , and Peter J. Bryant-A and ADGF-D are active adenosine deaminases (ADAs), and they cause polarization and serum

Â?urovec, Michal

207

Evidence That Release of Adenosine Triphosphate From Endothelial Cells During Increased Shear Stress Is Vesicular  

E-print Network

Evidence That Release of Adenosine Triphosphate From Endothelial Cells During Increased Shear: In response to increased shear stress, vascular endothelial cells release adenosine triphosphate (ATP, like that of nerve cells, is probably by vesicular exocytosis. Key Words: Endo- thelial cells--Quinacrine--Adenosine

Burnstock, Geoffrey

208

Ligand Interactions in the Adenosine Nucleotide-binding Domain of the Hsp90 Chaperone, GRP94  

E-print Network

Ligand Interactions in the Adenosine Nucleotide-binding Domain of the Hsp90 Chaperone, GRP94 II-terminal domain of eukaryotic Hsp90 proteins contains a conserved adenosine nucleotide binding pocket that also is essential for Hsp90 function, the molecular basis for adenosine nucleotide-dependent regulation of GRP94

Nicchitta, Chris

209

Interplay of Hypoxia and A 2B Adenosine Receptors in Tissue Protection  

Microsoft Academic Search

That adenosine signaling can elicit adaptive tissue responses during conditions of limited oxygen availability (hypoxia) is a long-suspected notion that recently gained general acceptance from genetic and pharmacologic studies of the adenosine signaling pathway. As hypoxia and inflammation share an interdependent relationship, these studies have demonstrated that adenosine signaling events can be targeted to dampen hypoxia-induced inflammation. Here, we build

Michael Koeppen; Tobias Eckle; Holger K. Eltzschig

2011-01-01

210

Interactive role of adenosine and dopamine in the opiate withdrawal syndrome  

Microsoft Academic Search

Adenosine reduces opioid withdrawal symptoms by activating A 1 adenosine receptors, probably by inhibiting excitatory amino acid release. Since blockade of A 2A adenosine receptors seems to enhance dopaminergic striatopallidal transmission, we evaluated the role of the purinergic system in the opiate withdrawal syndrome by using two A 1 receptor agonists [ N 6-cyclohexyladenosine, CHA and 2-chloro- N 6-cyclopentyladenosine, CCPA],

Luigi Stella; Vito de Novellis; Maria Redenta Vitelli; Annalisa Capuano; Filomena Mazzeo; Liberato Berrino; Francesco Rossi; Amelia Filippelli

2003-01-01

211

Evidence for an Adenosine Receptor on the Surface of Dog Coronary Myocytes  

Microsoft Academic Search

SUMMARY Adenosine and theophylline were linked covalently to oxidized stachyose to produce compounds too large to penetrate cell membranes. These compounds were used in two conscious and six open-chest anesthetized dogs to test the hypothesis that there is an adenosine receptor on the surface of the coronary myocyte. Intracor- onary infusions of the adenosine derivative produced dose-dependent coronary vasodilation which

RAY A. OLSSON; CHARLES J. DAVIS; EDWARD M. KHOURI; RANDOLPH E. PATTERSON

212

Activity-dependent Release of Endogenous Adenosine Modulates Synaptic Responses in the Rat Hippocampus  

Microsoft Academic Search

Adenosine is a potent inhibitory modulator of synaptic trans- mission in the CNS, but its role in normal physiological func- tion is unclear. In the present experiments, we have found electrophysiological evidence for activity-dependent re- lease of adenosine from hippocampal slices evoked by physiologically relevant stimulation, and have demonstrated that this adenosine modifies synaptic activity in this brain region. When

John B. Mitchell; Carl R. Lupica; Thomas V. Dunwiddie

1993-01-01

213

Adenosine receptors: G protein-mediated signalling and the role of accessory proteins  

Microsoft Academic Search

Ever since the discovery of the effects of adenosine in the circulation, adenosine receptors continue to represent a promising drug target. Firstly, this is due to the fact that the receptors are expressed in a large variety of cells; in particular, the actions of adenosine (or, respectively, of the antagonistic methylxanthines) in the central nervous system, in the circulation, on

Markus Klinger; Michael Freissmuth; Christian Nanoff

2002-01-01

214

Mechanisms of Adenosine Release in the Developing and Adult Mouse Hippocampus  

Microsoft Academic Search

Adenosine is a neuromodulator known to inhibit the synaptic release of neurotransmitters, e.g., glutamate, and to hyperpolarize postsynaptic neurons. The release of adenosine is markedly enhanced under ischemic conditions. It may then act as an endogenous neuroprotectant against cerebral ischemia and excitotoxic neuronal damage. The mechanisms by which adenosine is released from nervous tissue are not fully known, particularly in

Pirjo Saransaari; Simo S. Oja

2002-01-01

215

Development of adenosine sensor: effect of physiological buffers on activity and sensitivity in adenosine determinations by fast scan voltammetry.  

PubMed

A new fast scan voltammetry (FSV) method was tested in the determinations of adenosine in physiological buffers at pH 7.4. The buffers can be used in the determinations of adenosine in vivo and include 7 x 10(-2) M phosphate, Krebs-Henseleit (K-H) and Hanks' Balanced Salts (HBSS). A new method of fabrication of carbon fiber electrodes (CFEs) by polishing, followed by electrochemical pretreatment (ECP) was developed for the determination. After the ECP of CFE, CFE background current was stable in FSV determinations even though an increase in the background current was observed after the ECP in the buffers at pH 7.4. The sensitivity in FSV determinations of adenosine at the pretreated electrodes was tested in the physiological buffers at the potential scan rate of 500 V s(-1) at pH 7.4. Buffer composition and pH was the same during the ECP of CFE and in the FSV determinations. The sensitivity in the FSV determinations of adenosine at the new CFEs was high, compared to that previously reported at CFEs prepared by other methods, and showed a limited dependence on buffer composition. However, a small increase in buffer pH above 7.4 resulted in a decrease in sensitivity in the determinations of adenosine. The decrease in sensitivity was associated with an additional increase in CFE background current at pH > 7.4. At pH 7.4 best sensitivity and limit of detection was obtained in 7 x 10(-2) M phosphate buffer, where the background current was lowest. The sensitivity was half that in K-H and HBSS. Standard deviation of measurements was ca. 1%. The results demonstrate the feasibility of sensitive FSV determinations of adenosine in physiological buffers at pH 7.4 at CFEs. PMID:12964607

El-Nour, Kholoud Abou; Brajter-Toth, Anna

2003-08-01

216

The antiproliferative effect of 8-chloro-adenosine, an active metabolite of 8-chloro-cyclic adenosine monophosphate, and disturbances in nucleic acid synthesis and cell cycle kinetics  

Microsoft Academic Search

8-Chloro-adenosine, the dephosphorylated metabolite of the antineoplastic agent 8-chlorocyclic AMP, has been proposed to act on the regulatory subunits of cyclic AMP-dependent protein kinase. 8-Chloro-adenosine has a growth-inhibitory effect, the mechanism of which is unclear. We investigated the effects of 8-chloro-cyclic AMP and 8-chloro-adenosine on nucleic acid synthesis and cell cycle kinetics in two human glioma cell lines. These effects

Cornelis H. Langeveld; Cornelis A. M. Jongenelen; Johannes Wilhelmus M. Theeuwes; Johannes P. A. Baak; Johannes J. Heimans; Johannes C. Stoof; Godefridus J. Peters

1997-01-01

217

Binding of adenosine receptor ligands to brain of adenosine receptor knock-out mice: evidence that CGS 21680 binds to A 1 receptors in hippocampus  

Microsoft Academic Search

The adenosine receptor agonist 2-[ p-(2-carboxyethyl)phenylethylamino]-5?- N-ethylcarboxamidoadenosine (CGS 21680) is generally considered to be a selective adenosine A 2A receptor ligand. However, the compound has previously been shown to exhibit binding characteristics that are not compatible with adenosine A 2A receptor binding, at least in brain regions other than the striatum. We have examined binding of [ 3H]CGS 21680 and

Linda Halldner; Luisa V. Lopes; Elisabetta Daré; Karin Lindström; Björn Johansson; Catherine Ledent; Rodrigo A. Cunha; Bertil B. Fredholm

2004-01-01

218

Effects of liposome-entrapped adenosine in the isolated rat aorta.  

PubMed

This study examined the effects of adenosine- and adenosine deaminase-loaded liposomes upon the contractile activity of the vascular smooth muscle, using the isolated, de-endothelised rat aorta ring as in vitro model. While control liposomes had no effect, intraliposomal adenosine (5 x 10(-3) M) induced contraction of the preparation. Intraliposomal adenosine deaminase induced partial relaxation of high K(+)-precontracted rings. The adenosine-induced contraction seems to involve Ca2+ influx through L-type channels as an essential component, but protein kinase C may also have a modulatory role. PMID:8112411

Brailoiu, E; Serban, D N; Slatineanu, S; Filipeanu, C M; Petrescu, B C; Branisteanu, D D

1993-12-21

219

Role of Extracellular Adenosine in Acute Lung Injury  

NSDL National Science Digital Library

Acute lung injury (ALI) is a lung disease characterized by pulmonary edema and severe hypoxia. The past decade hosted a search for endogenous mechanisms controlling lung inflammation and pulmonary edema during ALI. As such, recent evidence indicates extracellular adenosine in orchestrating the resolution of pulmonary edema and inflammation during ALI.

Tobias Eckle (University of Colorado Denver Anesthesiology, Mucosal Inflammation Program); Michael Koeppen (University of Colorado Denver Anesthesiology); Holger K. Eltzschig (University of Colorado Denver Anesthesiology)

2009-10-01

220

Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesis  

PubMed Central

Epigenetic modifications, including changes in DNA methylation, lead to altered gene expression and thus may underlie epileptogenesis via induction of permanent changes in neuronal excitability. Therapies that could inhibit or reverse these changes may be highly effective in halting disease progression. Here we identify an epigenetic function of the brain’s endogenous anticonvulsant adenosine, showing that this compound induces hypomethylation of DNA via biochemical interference with the transmethylation pathway. We show that inhibition of DNA methylation inhibited epileptogenesis in multiple seizure models. Using a rat model of temporal lobe epilepsy, we identified an increase in hippocampal DNA methylation, which correlates with increased DNA methyltransferase activity, disruption of adenosine homeostasis, and spontaneous recurrent seizures. Finally, we used bioengineered silk implants to deliver a defined dose of adenosine over 10 days to the brains of epileptic rats. This transient therapeutic intervention reversed the DNA hypermethylation seen in the epileptic brain, inhibited sprouting of mossy fibers in the hippocampus, and prevented the progression of epilepsy for at least 3 months. These data demonstrate that pathological changes in DNA methylation homeostasis may underlie epileptogenesis and reversal of these epigenetic changes with adenosine augmentation therapy may halt disease progression. PMID:23863710

Williams-Karnesky, Rebecca L.; Sandau, Ursula S.; Lusardi, Theresa A.; Lytle, Nikki K.; Farrell, Joseph M.; Pritchard, Eleanor M.; Kaplan, David L.; Boison, Detlev

2013-01-01

221

Adenosine to inosine RNA editing in animal cells  

Microsoft Academic Search

Major advances in the understanding of adenosine deaminases acting on RNA (ADARs) have come from the generation of ADAR mutant animals. In mice, ADAR1 is a widely expressed essential gene and loss of function in embryos leads to apoptosis through unknown mechanisms in many different cell types. Mammalian ADAR2 is required primarily to edit glutamate receptor transcripts in the nervous

Barry Hoopengardner; Mary O’Connell; Robert Reenan; Liam Keegan

222

Laser photobleaching leads to a fluorescence grade adenosine deaminase  

SciTech Connect

The enzyme adenosine deaminase (adenosine aminohydrolase EC 3.5.4.4) from calf intestinal mucosa is commercially available at high purity grade yet, at the sensitivity at which fluorescence studies may be undertaken, a nonpeptidic fluorescence is detectable at lambda exmax = 350 nm and lambda emmax = 420 nm. A sevenfold decrease of this nonpeptidic fluorescence was obtained upon irradiation by the third harmonic (355 nm) of a Nd:YAG laser for 16 min, at 5 mJ/pulse, with a pulse width of 6 ns at a repetition rate of 10 Hz. The decline of fluorescence was accompanied by a negligible loss of enzymatic activity. Moreover, the integrity of the protein was ascertained by (i) its fluorescence (lambda exmax = 305 nm, lambda emmax = 335 nm) and lifetime distribution and (ii) its kinetics in the presence of the substrate adenosine and two inhibitors, all of which remained essentially unaltered. Laser photobleaching is a simple way to achieve a fluorescence grade adenosine deaminase.

Parola, A.H.; Caiolfa, V.R.; Bar, I.; Rosenwaks, S. (Ben Gurion Univ. of the Negev, Beer Sheva (Israel))

1989-09-01

223

AMINOHYDROLASES ACTING ON ADENINE, ADENOSINE AND THEIR DERIVATIVES  

Microsoft Academic Search

Background: Adenine and adenosine-acting aminohydrolases are important groups of enzymes responsible for the metabolic salvage of purine compounds. Several subclasses of these enzymes have been described and given current knowledge of the full genome sequences of many organisms, it is possible to identify genes encoding these enzymes and group them according to their primary structure. Methods and Results: This article

Hana Pospisilova; Ivo Frebort

224

Adenosine: a potential mediator of immunosuppression in multiple organ failure  

Microsoft Academic Search

Multiple organ failure following a variety of insults, including, trauma, shock and pancreatitis, is the cause of 50–80% of all deaths in surgical intensive care units. In most patients, infections secondary to a general immunosuppressive state serve to trigger the development of multiple organ failure. This immunosuppressive state may be a consequence of excessive release of adenosine into the extracellular

György Haskó; Edwin A Deitch; Csaba Szabó; Zoltán H Németh; E. Sylvester Vizi

2002-01-01

225

Adenosine A1 receptor activation inhibits LTP in sympathetic ganglia.  

PubMed

The effects of adenosine on long-term potentiation of sympathetic ganglia was studied in the isolated superior cervical ganglion of the rat, using extracellularly recorded compound action potential as an index of synaptic transmission. Adenosine in a small concentration (2 microM) blocked the post-tetanic potentiation without affecting long-term potentiation. Higher concentrations blocked both responses with no significant effect on basal transmission. The inhibitory effect appears to be due to activation of adenosine A1 receptors. This was indicated by results from experiments with the A1 agonist N6-cyclopentyladenosine (1 microM) which caused inhibition of the basal transmission as well as long-term potentiation and post-tetanic potentiation. This inhibition was readily antagonized by 8-phenyltheophylline (1 microM), an A1 receptor antagonist. A small enhancement of basal transmission was seen on treatment with 8-phenyltheophylline. The inhibitory effect of N6-cyclopentyladenosine on long-term potentiation was totally prevented when the Ca2+ concentration in the superfusate was doubled (from 2.2 to 4.4 mM). The adenosine A2 receptor agonist 5'-(N-cyclopropyl)-carboxamidoadenosine (1 microM), although caused a slight potentiation of basal transmission, had no significant effect on the post-tetanic potentiation or long-term potentiation. The adenosine transport inhibitors, dipyridamole (2 microM) and S-(4-nitorobenzyl)-6-thioinosine (2 microM) caused significant inhibition of the basal ganglionic transmission without affecting post-tetanic potentiation or long-term potentiation. The effect of dipyradimole on basal transmission was not antagonized in the presence of 8-phenyltheophylline suggesting a non-specific action. The results suggest that exogenous adenosine can inhibit both post-tetanic potentiation and long-term potentiation in sympathetic ganglia, probably by activation of presynaptic A1 receptors. The results also suggest that endogenous adenosine, which is probably released in minute amounts, may only modulate basal transmission without influencing induction or maintenance of long-term potentiation in the superior cervical ganglion. PMID:9756986

Hogan, Y H; Hawkins, R; Alkadhi, K A

1998-10-01

226

Contribution of adenosine to arteriolar autoregulation in striated muscle.  

PubMed

The contribution of adenosine to blood flow autoregulation in striated muscle was evaluated by direct in vivo visualization of arterioles in the rat cremaster muscle. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium, and the cremaster muscle was surgically exposed and maintained in a controlled tissue bath environment with pH 7.40, CO2 tension (PCO2) congruent to 40 mmHg, and O2 tension (PO2) at either a high (congruent to 70 mmHg) or a low (congruent to 10 mmHg) value. Local adenosine activity was blocked in some animals by the addition of theophylline (3 X 10(-5) M) to the bath medium. Individual second (2A)- and third (3A)-order arterioles were observed via closed-circuit television microscopy, and blood flow in each arteriole was calculated from simultaneous measurements of arteriolar diameter and red blood cell velocity. Perfusion pressure to the animal's hindquarters was altered by varying the degree of occlusion of the sacral aorta; arteriolar diameter, velocity, and blood flow responses were plotted as a function of the varying pressure. Both 2A and 3A arterioles exhibited vasodilation and substantial superregulation of blood flow (increased blood flow with decreased perfusion pressure) when bath PO2 was low and adenosine activity was not blocked. Addition of theophylline to the cremaster bath medium significantly reduced the dilation and abolished superregulation, although substantial autoregulation remained. When bath PO2 was high, the degree of arteriolar dilation and autoregulation was reduced compared with the low bath PO2 responses, and blocking adenosine activity had no effect on the responses. These results support the concept that changes in local adenosine levels are involved in the autoregulatory responses observed in the rat cremaster muscle and that the magnitude of adenosine's contribution is directly related to the degree of tissue hypoxia. However, blocking adenosine activity did not totally abolish autoregulation, suggesting that other metabolic and/or myogenic factors may also be contributing to blood flow regulation in this tissue. PMID:6837757

Morff, R J; Granger, H J

1983-04-01

227

Crystal Structures of T. b. rhodesiense Adenosine Kinase Complexed with Inhibitor and Activator: Implications for Catalysis and Hyperactivation  

Microsoft Academic Search

BackgroundThe essential purine salvage pathway of Trypanosoma brucei bears interesting catalytic enzymes for chemotherapeutic intervention of Human African Trypanosomiasis. Unlike mammalian cells, trypanosomes lack de novo purine synthesis and completely rely on salvage from their hosts. One of the key enzymes is adenosine kinase which catalyzes the phosphorylation of ingested adenosine to form adenosine monophosphate (AMP) utilizing adenosine triphosphate (ATP)

Sabine Kuettel; Jason Greenwald; Dirk Kostrewa; Shaheen Ahmed; Leonardo Scapozza; Remo Perozzo

2011-01-01

228

Metabolic changes of cultured DRG neurons induced by adenosine using confocal microscopy imaging  

NASA Astrophysics Data System (ADS)

Adenosine exerts multiple effects on pain transmission in the peripheral nervous system. This study was performed to use confocal microscopy to evaluate whether adenosine could affect dorsal root ganglia (DRG) neurons in vitro and test which adenosine receptor mediates the effect of adenosine on DRG neurons. After adding adenosine with different concentration, we compared the metabolic changes by the real time imaging of calcium and mitochondria membrane potential using confocal microscopy. The results showed that the effect of 500 ?M adenosine on the metabolic changes of DRG neurons was more significant than others. Furthermore, four different adenosine receptor antagonists were used to study which receptor mediated the influences of adenosine on the cultured DRG neurons. All adenosine receptor antagonists especially A1 receptor antagonist (DPCPX) had effect on the Ca2+ and mitochondria membrane potential dynamics of DRG neurons. The above studies demonstrated that the effect of adenosine which may be involved in the signal transmission on the sensory neurons was dose-dependent, and all the four adenosine receptors especially the A1R may mediate the transmission.

Zheng, Liqin; Huang, Yimei; Chen, Jiangxu; Wang, Yuhua; Yang, Hongqin; Zhang, Yanding; Xie, Shusen

2012-12-01

229

Transendothelial transport and metabolism of adenosine and inosine in the intact rat aorta  

SciTech Connect

This study was aimed at defining the role of vascular endothelium in the transport and metabolism of adenosine. For this purpose, endothelium-intact and endothelium-denuded isolated rat aortas, perfused at constant flow (2 ml/min), were prelabeled with 3H-adenosine or 3H-inosine for 10 minutes at concentrations of 0.012-100 microM. Sequestration of adenosine by endothelium was determined from radioactivity recovered during selective endothelial cell removal with deoxycholic acid (0.75% for 15 seconds). In the physiological concentration range of adenosine (0.012-1 microM), fractional sequestration by endothelium was 90-92% of the total adenosine incorporation by the aorta. Endothelial sequestration of inosine at 0.1 microM was 85%. At 100 microM adenosine or inosine, fractional sequestration by aortic endothelium was 33% and 39%, respectively. Analysis of the specific radioactivity of adenine nucleotides extracted from prelabeled aortas indicated that most of the adenosine was incorporated into endothelial adenine nucleotides. Incorporation of inosine into endothelial ATP was approximately 15% that of adenosine. Inhibition of aortic adenosine deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) did not influence sequestration of 0.1 microM adenosine, but resulted in a 49% reduction of total endothelial incorporation at 100 microM adenosine. Transfer of radioactive purines from the endothelium to underlying smooth muscle after prelabeling was equivalent to only 1%/hr of total endothelial radioactivity.

Kroll, K.; Kelm, M.K.; Buerrig, K.F.S.; Schrader, J.

1989-06-01

230

Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling  

SciTech Connect

It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine ((R)-AHPIA) into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling.

Lohse, M.J.; Klotz, K.N.; Schwabe, U.

1991-04-01

231

Regional haemodynamic responses to adenosine receptor activation vary across time following lipopolysaccharide treatment in conscious rats  

PubMed Central

Background and purpose: Studies using adenosine receptor antagonists have shown that adenosine-mediated vasodilatations play an important role in the maintenance of regional perfusion during sepsis, but it is unclear whether vascular sensitivity to adenosine is affected. Here, we assessed regional haemodynamic responses to adenosine agonists and antagonists in normal and lipopolysaccharide (LPS)-treated rats to investigate a possible role for adenosine in the haemodynamic sequelae. Experimental approach: Male Sprague–Dawley rats were chronically instrumented with pulsed Doppler flow probes to measure regional haemodynamic responses to adenosine-receptor agonists (adenosine, 2-choloro-N6-cyclopentyladenosine (CCPA)) and antagonists (8-phenyltheophylline (8-PT), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), at selected time points in control and LPS-treated rats. Key results: The responses to 8-PT were consistent with endogenous adenosine causing bradycardia, and renal and hindquarters vasodilatation in control rats, whereas in LPS-treated rats, there was evidence for endogenous adenosine causing renal (at 1.5?h) and hindquarters (at 6?h) vasoconstriction. In control animals, exogenous adenosine caused hypotension, tachycardia and widespread vasodilatation, whereas in LPS-treated rats, the adenosine-induced renal (at 1.5?h) and hindquarters (at 6?h) vasodilatations were abolished. As enhanced A1 receptor-mediated vasoconstriction could explain the results in LPS-treated rats, vascular responsiveness to a selective A1-receptor agonist (CCPA) or antagonist (DPCPX) was assessed. There was no evidence for enhanced vasoconstrictor responsiveness to CCPA in LPS-treated rats, but DPCPX caused renal vasodilatation, consistent with endogenous adenosine mediating renal vasoconstriction under these conditions. Conclusions and implications: The results show changes in adenosine receptor-mediated cardiovascular effects in endotoxaemia that may have implications for the use of adenosine-based therapies in sepsis. PMID:18500354

Jolly, L; March, J E; Kemp, P A; Bennett, T; Gardiner, S M

2008-01-01

232

Effect of adenosine on bicuculline-resistant paired-pulse inhibition in the rat hippocampal slice.  

PubMed

This study extends previous investigations into the effect of adenosine on bicuculline-resistant paired-pulse inhibition between field potentials evoked 300 ms apart in the CA1 area of the rat hippocampal slice. A direct assessment of the effect of adenosine on paired-pulse inhibition is complicated by the facts that adenosine directly depresses evoked potentials and bicuculline-resistant paired-pulse inhibition is greater between pairs of small potentials than between pairs of larger potentials. Adenosine increased bicuculline-resistant paired-pulse inhibition when stimulus strength was constant between adenosine and control but paired-pulse inhibition of responses in adenosine was markedly less than paired-pulse inhibition of control responses of the same size. Furthermore, adenosine decreased the size of conditioned potentials to a significantly lesser extent than unpaired potentials of the same initial size. Taken together the results indicate that adenosine can decrease bicuculline-resistant paired-pulse inhibition in the hippocampus. A possible mechanism for this effect is that adenosine is suppressing transmission at excitatory terminals onto interneurones which would suggest that these receptors are more sensitive to adenosine than those on the Schaffer collateral/CA1 pyramidal cell synapses. In this case adenosine should reduce paired-pulse inhibition at lower concentrations than are required for depression of single evoked potentials. A comparison of the concentration-response relationships for the effects of adenosine on paired-pulse inhibition and on single evoked potentials ruled out greater sensitivity of adenosine receptors at excitatory terminals onto interneurones as an explanation for adenosine's action on bicuculline-resistant paired-pulse inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7550616

Higgins, M J; Stone, T W

1995-01-01

233

Adenosine receptor control of cognition in normal and disease.  

PubMed

Adenosine and adenosine receptors (ARs) are increasingly recognized as important therapeutic targets for controlling cognition under normal and disease conditions for its dual roles of neuromodulation as well as of homeostatic function in the brain. This chapter first presents the unique ability of adenosine, by acting on the inhibitory A1 and facilitating A2A receptor, to integrate dopamine, glutamate, and BNDF signaling and to modulate synaptic plasticity (e.g., long-term potentiation and long-term depression) in brain regions relevant to learning and memory, providing the molecular and cellular bases for adenosine receptor (AR) control of cognition. This led to the demonstration of AR modulation of social recognition memory, working memory, reference memory, reversal learning, goal-directed behavior/habit formation, Pavlovian fear conditioning, and effort-related behavior. Furthermore, human and animal studies support that AR activity can also, through cognitive enhancement and neuroprotection, reverse cognitive impairments in animal models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and schizophrenia. Lastly, epidemiological evidence indicates that regular human consumption of caffeine, the most widely used psychoactive drug and nonselective AR antagonists, is associated with the reduced cognitive decline in aging and AD patients, and with the reduced risk in developing PD. Thus, there is a convergence of the molecular studies revealing AR as molecular targets for integrating neurotransmitter signaling and controlling synaptic plasticity, with animal studies demonstrating the strong procognitive impact upon AR antagonism in normal and disease brains and with epidemiological and clinical evidences in support of caffeine and AR drugs for therapeutic modulation of cognition. Since some of adenosine A2A receptor antagonists are already in phase III clinical trials for motor benefits in PD patients with remarkable safety profiles, additional animal and human studies to better understand the mechanism underlying the AR-mediated control of cognition under normal and disease conditions will provide the required rationale to stimulate the necessary clinical investigation to rapidly translate adenosine and AR drug as a novel strategy to control memory impairment in neuropsychiatric disorders. PMID:25175970

Chen, Jiang-Fan

2014-01-01

234

Adenosine Kinase Inhibitor Design Bull. Korean Chem. Soc. 2007, Vol. 28, No. 4 561 Adenosine Kinase Inhibitor Design Based on Pharmacophore Modeling  

E-print Network

Scramble method. Thus, the Hypo1 was exploited for searching new lead compounds over 238,819 chemical compounds) inhibitors, Pharmacophore hypotheses, New lead search, Computer-aided drug design Introduction Adenosine (ADO including neuro- degeneration, seizures, ischemia, inflammation and pain.7 Adenosine kinase (AK

Lee, Keun Woo

235

Characterization of cardiac adenosine receptors using N/sup 6/-phenyladenosines and a new radioligand, (/sup 125/I)-(m-aminophenyl)adenosine  

SciTech Connect

The chick heart contains adenosine receptors with characteristics similar to the R adenosine receptors found in the CNS. They have synthesized several N/sup 6/-phenyladenosines and tested their potencies for inhibiting the binding of (/sup 125/I)(p-aminobenzyl)adenosine )(/sup 125/I)ABA) to chick heart membranes. Of the 12 compounds tested, N/sup 6/-(p-aminobenzyl) adenosine (ABA) was the least potent (IC/sub 50/ approx. 40 nM) while N/sup 6/-(m-nitrophenyl)adenosine(MNPA) was the most potent (IC/sub 50/ approx. 1 nM). The IC/sub 50/ of N/sup 6/-(m-aminophenyl)adenosine(MAPA) was greater than that of N/sup 6/-phenyladenosine(PA) while that of MNPA was less than that of PA. The effects of these electron-releasing (-NH/sub 2/) and electron-withdrawing (-NO/sub 2/) groups along with data obtained with other phenyl-substituted N/sup 6/-phenyladenosines suggest that the electron density of the N/sup 6/-nitrogen may affect the affinities of these compounds for the cardiac adenosine receptor. MAPA can be iodinated to produce a new ligand, (/sup 125/I)MAPA. This iodination, like that of ABA, increases the affinity of the compound and produces a ligand with good affinity and low nonspecific binding suitable for studies on tissues with low concentrations of adenosine receptors.

Kwatra, M.M.; Hosey, M.M.; Green, R.

1986-03-05

236

Multiple effects of adenosine in the arterially perfused mammalian eye. Possible mechanisms for the neuroprotective function of adenosine in the retina  

Microsoft Academic Search

It has been postulated that the major physiological role of adenosine is protection of the central nervous system in conditions such as ischemia, hypoxia, or prolonged neuronal excitation. Under these conditions adenosine is released, and exerts multiple effects, including vasodilation, inhibition of neuronal activity, and enhancement of glycogenolysis, resulting in neuroprotection. In this article, published as well as unpublished data

Claudio Macaluso; Laura J. Frishman; Beatrice Frueh; Alain Kaelin-Lang; Shoken Onoe; Günter Niemeyer

2003-01-01

237

Colorimetric Determination of the Purity of 3?-Phospho Adenosine 5?-Phosphosulfate and Natural Abundance of 3?-Phospho Adenosine 5?Phosphate at Picomole Quantities  

Microsoft Academic Search

This work presents novel colorimetric methods not only to measure 3?-phospho adenosine 5?-phosphate (PAP) and 3?-phospho adenosine 5?-phosphosulfate (PAPS) in the range of picomoles, but also to determine the purity of PAPS or PAP contaminants in PAPS in the range of nanomoles. These methods exploit the availability of overexpressed phenol sulfotransferase (PST) and the fact that sulfuryl group transfer requires

En-Shyh Lin; Yuh-Shyong Yang

1998-01-01

238

Neuronal A1 receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion.  

PubMed

The naturally occurring purine nucleoside adenosine has pronounced anticonvulsant and neuroprotective properties and plays a neuromodulatory role in the CNS. Kynurenic acid (KYNA) is an astrocyte-derived, endogenous neuroinhibitory compound, which shares several of adenosine's properties. In a first attempt to examine possible interactions between these two biologically active molecules, adenosine was focally applied into the striatum of freely moving rats by reverse microdialysis, and changes in extracellular KYNA were monitored over time. A 2-h infusion of adenosine increased KYNA levels in a dose-dependent manner, with 10 mm of adenosine causing a twofold elevation within 1 h. This effect was reversible and was effectively blocked by coinfusion of the specific A1 adenosine receptor antagonist 8-cyclopentyltheophylline (100 microm). In contrast, coinfusion of adenosine with MSX-3 (100 microm), an A2A receptor antagonist, did not affect the adenosine-induced increase in KYNA levels. Local striatal perfusion with the A1 receptor agonist N6-cyclopentyladenosine (100 microm) mimicked the effect of adenosine, whereas perfusion with the A2A receptor agonist CGS-21680 (100 microm) was ineffective. Finally, we tested the effect of adenosine (10 mm) on extracellular KYNA in striata that had been injected with quinolinate (60 nmol/1 microL) 7 days earlier. In this neuron-depleted tissue, perfusion with adenosine failed to affect extracellular KYNA levels. These data demonstrate that adenosine is capable of raising extracellular KYNA in the rat striatum by interacting with postsynaptic neuronal A1 receptors. This mechanism may result in a synergism between the neurobiological effects of adenosine and KYNA. PMID:15255939

Wu, Hui-Qiu; Fuxe, Kjell; Schwarcz, Robert

2004-08-01

239

Antiparasitic effect of calcium and magnesium ion-free buffer treatments against a common monogenean Neobenedenia girellae.  

PubMed

This study investigated a new effective method for controlling the capsalid monogenean Neobenedenia girellae. We examined in vitro and in vivo the effect on the percentage survival of N. girellae in buffers containing different metallic ions. Decreased survival was observed in buffer solutions lacking two ions. In particular, the percentage survival of N. girellae was significantly decreased after 10 min exposure to buffer containing neither Ca(2+) nor Mg(2+). Transmission electron microscopic observations showed that treatment with this buffer disrupted intercellular junctions. This significant effect on percentage survival of N. girellae using Ca(2+)/Mg(2+)-free buffer was confirmed in an in vivo assay. Ca(2+)/Mg(2+)-free buffer had no effect on the condition of the host, spotted halibut Verasper variegates (Pleuronectidae). These results suggest that treatment with Ca(2+)/Mg(2+)-free buffer is a new effective control method, which could replace existing control methods. PMID:17032471

Ohashi, H; Umeda, N; Hirazawa, N; Ozaki, Y; Miura, C; Miura, T

2007-02-01

240

Intravenous Calcium and Magnesium for Oxaliplatin-Induced Sensory Neurotoxicity in Adjuvant Colon Cancer: NCCTG N04C7  

PubMed Central

Purpose Cumulative sensory neurotoxicity (sNT) is the dose-limiting toxicity of oxaliplatin, which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant settings. In a nonrandomized, retrospective study, intravenous (IV) calcium/magnesium (Ca/Mg) was associated with reduced oxaliplatin-induced sNT. Methods Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) were randomly assigned to Ca/Mg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo, in a double-blinded manner. The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria. An oxaliplatin-specific sNT scale and patient questionnaires were also used to assess sNT. After 104 of 300 planned patients were enrolled, the study was closed. This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy; these data were subsequently found to be incorrect. Results Overall, 102 patients were available for analysis. Ca/Mg decreased the incidence of chronic, cumulative, grade 2 or greater sNT, as measured by NCI CTCAE (P = .038) and also by the oxaliplatin-specific sNT scale (P = .018). In addition, acute muscle spasms associated with oxaliplatin were significantly reduced (P = .01) No effect on acute, cold-induced sNT was found. No substantial differences in adverse effects were noted between Ca/Mg and placebo. Conclusion Despite early termination and decreased statistical power, this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer. PMID:21189381

Grothey, Axel; Nikcevich, Daniel A.; Sloan, Jeff A.; Kugler, John W.; Silberstein, Peter T.; Dentchev, Todor; Wender, Donald B.; Novotny, Paul J.; Chitaley, Umesh; Alberts, Steven R.; Loprinzi, Charles L.

2011-01-01

241

Evaluation of the content and bioaccessibility of iron, zinc, calcium and magnesium from groats, rice, leguminous grains and nuts.  

PubMed

The objective of this study was to determine the content and the bioaccessibility of minerals (Fe, Zn, Ca and Mg) in commonly consumed food products, such as cereal groats, rice, leguminous grains and nuts purchased from the local market. The contents of Fe, Zn, Ca and Mg in foods were assayed after dry ashing of samples, while the bioaccessibility of these minerals after enzymatic in vitro digestion, was determined by flame atomic absorption spectrometry. A relatively high content of Fe was found in cashew nuts and green lentils, while cashew nuts and buckwheat groats had the highest concentration of Zn. It was found that the highest amount of macro-elements was generally in nuts, in particular: brazil nuts (Ca and Mg), cashews (Mg) and hazelnuts (Ca and Mg). Concerning the mineral bioaccessibility, the highest values for Fe were obtained in cashew nuts and green lentils (2.8 and 1.7 mg/100 g), for Zn in green lentils (2.1 mg/100 g), for Ca in brazil nuts and shelled pea (32.6 and 29.1 mg/100 g), while for Mg in shelled peas and green lentils (43.4 and 33.9 mg/100 g). Generally, the best sources of bioaccessible minerals seem to be leguminous grains and nuts. PMID:24587537

Suliburska, Joanna; Krejpcio, Zbigniew

2014-03-01

242

Structural basis for calcium and magnesium regulation of a large conductance calcium-activated potassium channel with ?1 subunits.  

PubMed

Large conductance Ca(2+)- and voltage-activated potassium (BK) channels, composed of pore-forming ? subunits and auxiliary ? subunits, play important roles in diverse physiological activities. The ?1 is predominately expressed in smooth muscle cells, where it greatly enhances the Ca(2+) sensitivity of BK channels for proper regulation of smooth muscle tone. However, the structural basis underlying dynamic interaction between BK mSlo1 ? and ?1 remains elusive. Using macroscopic ionic current recordings in various Ca(2+) and Mg(2+) concentrations, we identified two binding sites on the cytosolic N terminus of ?1, namely the electrostatic enhancing site (mSlo1(K392,R393)-?1(E13,T14)), increasing the calcium sensitivity of BK channels, and the hydrophobic site (mSlo1(L906,L908)-?1(L5,V6,M7)), passing the physical force from the Ca(2+) bowl onto the enhancing site and S6 C-linker. Dynamic binding of these sites affects the interaction between the cytosolic domain and voltage-sensing domain, leading to the reduction of Mg(2+) sensitivity. A comprehensive structural model of the BK(mSlo1 ?-?1) complex was reconstructed based on these functional studies, which provides structural and mechanistic insights for understanding BK gating. PMID:24764303

Liu, Hao-Wen; Hou, Pan-Pan; Guo, Xi-Ying; Zhao, Zhi-Wen; Hu, Bin; Li, Xia; Wang, Lu-Yang; Ding, Jiu-Ping; Wang, Sheng

2014-06-13

243

Estimation of calcified tissues hardness via calcium and magnesium ionic to atomic line intensity ratio in laser induced breakdown spectra  

NASA Astrophysics Data System (ADS)

Calcified tissues representing three different matrices, namely enamel of human teeth, shells and eggshell, have been studied via Laser Induced Breakdown Spectroscopy (LIBS) technique. The experimental CaII/CaI and MgII/MgI ratios have been measured, in view of the expected correlation between the extent of ionization caused by the laser induced shock wave (SW) and the hardness of the target. The ratio CaII/CaI between the ionic calcium line at 373.69 nm and the neutral line at 428.9 nm is obtained for enamel, shells and eggshell spectra, as well as the ratio MgII/MgI between the ionic magnesium line at 280.26 nm and the neutral line at 285.22 nm. The results show that such spectral lines intensities ratio differs for different matrices and is indeed related to the target materials hardness. It is also found that the MgII/MgI ratio is preferable as an indicator of hardness since these lines are less affected by self absorption. The SW front speed has been measured in the three cases and the obtained values confirm the proportionality to the target hardness. The results here obtained suggest the feasibility of the quantitative estimation of hardness for any other calcified tissues.

Abdel-Salam, Z. A.; Galmed, A. H.; Tognoni, E.; Harith, M. A.

2007-12-01

244

Serum Zinc, Copper, Selenium, Calcium, and Magnesium Levels in Pregnant and Non-Pregnant Women in Gondar, Northwest Ethiopia  

Microsoft Academic Search

Pregnant women in developing countries are vulnerable to multiple micronutrient deficiencies. Studies assessing serum levels\\u000a of the micronutrients and magnitude of their deficiencies are very scarce in African subjects. This study was aimed at determining\\u000a serum levels of micronutrients in 375 pregnant (42 HIV seropositive) and 76 non-pregnant women (20 HIV seropositive) who visited\\u000a the University of Gondar Hospital, Gondar,

Afework Kassu; Tomoki Yabutani; Andargachew Mulu; Belay Tessema; Fusao Ota

2008-01-01

245

Influence of NPK fertilization on calcium and magnesium in Poa pratensis L. with reference to dietary requirements of grazing cattle  

Microsoft Academic Search

A two?year experiment was conducted on Edwards muck (Limnic Medisaprist) on the Pinney?Purdue Agricultural Center at Wanatah, Indiana to study the effect of NPK fertilization on Ca and Mg concentrations in Kentucky bluegrass (Poa pratensis L.). Eight combinations of N?P?K fertilizer (0–0–0, 0–99–0, 0–0–372, 0–99–372, 168–0–0, 168–99–0, 168–0–372, 168–99–372 kg\\/ha), were applied each spring. Four cuttings were taken annually during

J. W. Lightner; C. L. Rhykerd; D. B. Mengel; G. E. Van Scoyoc; E. L. Hood; C. H. Noller

1983-01-01

246

Adenosine receptor antagonist and augmented vasodilation during hypoxic exercise  

PubMed Central

We tested the hypothesis that adenosine contributes to augmented skeletal muscle vasodilation during hypoxic exercise. In separate protocols, subjects performed incremental rhythmic forearm exercise (10% and 20% of maximum) during normoxia and normocapnic hypoxia (80% arterial O2 saturation). In protocol 1 (n = 8), subjects received an intra-arterial administration of saline (control) and aminophylline (adenosine receptor antagonist). In protocol 2 (n = 10), subjects received intra-arterial phentolamine (?-adrenoceptor antagonist) and combined phentolamine and aminophylline administration. Forearm vascular conductance (FVC; in ml·min?1·100 mmHg?1) was calculated from forearm blood flow (in ml/min) and blood pressure (in mmHg). In protocol 1, the change in FVC (?FVC; change from normoxic baseline) during hypoxic exercise with saline was 172 ± 29 and 314 ± 34 ml·min?1·100 mmHg?1 (10% and 20%, respectively). Aminophylline administration did not affect ?FVC during hypoxic exercise at 10% (190 ± 29 ml·min?1·100 mmHg?1, P = 0.4) or 20% (287 ± 48 ml·min?1·100 mmHg?1, P = 0.3). In protocol 2, ?FVC due to hypoxic exercise with phentolamine infusion was 313 ± 30 and 453 ± 41 ml·min?1·100 mmHg?1 (10% and 20% respectively). ?FVC was similar at 10% (352 ± 39 ml·min?1·100 mmHg?1, P = 0.8) and 20% (528 ± 45 ml·min?1·100 mmHg?1, P = 0.2) hypoxic exercise with combined phentolamine and aminophylline. In contrast, ?FVC to exogenous adenosine was reduced by aminophylline administration in both protocols (P < 0.05 for both). These observations suggest that adenosine receptor activation is not obligatory for the augmented hyperemia during hypoxic exercise in humans. PMID:19661449

Madery, Brandon D.; Pike, Tasha L.; Eisenach, John H.; Dietz, Niki M.; Joyner, Michael J.; Wilkins, Brad W.

2009-01-01

247

Adenosine signaling in striatal circuits and alcohol use disorders.  

PubMed

Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction. PMID:23912595

Nam, Hyung Wook; Bruner, Robert C; Choi, Doo-Sup

2013-09-01

248

Modulation of glial cell signaling by adenosine and pharmacological reinforcement  

Microsoft Academic Search

In view of the increasing evidence that a pathological glial activation plays a significant role in the development of neurodegenerative\\u000a diseases, we investigated the underlying molecular signaling as a possible target for a pharmacological therapy. Here, we\\u000a are particularly focusing on the endogenous modulation of the Ca2+ and cyclic nucleotide-dependent signaling by the nucleoside adenosine and its reinforcement by the

P. Schubert; T. Ogata; S. Ferroni; A. McRae; Y. Nakamura; K. Rudolphi

1996-01-01

249

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders  

PubMed Central

Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction. PMID:23912595

Nam, Hyung Wook; Bruner, Robert C.; Choi, Doo-Sup

2013-01-01

250

Inhibition of platelet aggregation by adenosine receptor agonists  

Microsoft Academic Search

2-(Ar)alkoxyadenosines, which are agonists selective for the A2AAR in PC 12 cell and rat striatum membranes, are also agonists at the A2AR coupled to adenylate cyclase (AC) that mediates the inhibition of platelet aggregation. A panel of twelve well-characterized\\u000a adenosine analogues stimulated human platelet AC and inhibited ADP-induced platelet aggregation at sub- to low-micromolar\\u000a concentrations with a potency ranking CGS

Gloria Cristalli; Sauro Vittori; Robert D. Thompson; William L. Padgett; Dan Shi; John W. Daly; Ray A. Olsson

1994-01-01

251

Molecularly imprinted hybrid adsorbents for adenine and adenosine-5'-triphosphate.  

PubMed

Submicrometer-sized silica gel particles were coated with a polyanion and a polycation bearing thymine chromophores. The polymer-coated particles were found to selectively adsorb adenine and adenosine-5'-triphosphate (ATP), as compared to other nucleobases and nucleotides, respectively. The adsorption was enhanced by the irradiation of the particles in the presence of adenine which resulted in the molecular imprinting of adenine. ATP adsorption was strongly pH-dependent. PMID:22994134

Plewa, Anna; Yusa, Shin-Ichi; Szuwarzy?ski, Micha?; Szczubia?ka, Krzysztof; Morishima, Yotaro; Nowakowska, Maria

2012-10-25

252

Adenosine: A Partial Agonist of the Growth Hormone Secretagogue Receptor  

Microsoft Academic Search

The growth hormone secretagogue receptor (GHS-R) is involved in the regulation of pulsatile GH release. However, until recently, natural endogenous ligands for the receptor were unknown. We fractionated porcine hypothalamic extracts and assayed fractions for activity on HEK293 cells expressing GHS-R and aequorin. A partial agonist was isolated and identified using microspray tandem mass spectrometry as adenosine. GHS-R activation by

Roy G. Smith; Patrick R. Griffin; Yuan Xu; Alexander G. A. Smith; Ken Liu; Jimmy Calacay; Scott D. Feighner; C.-S. Pong; Denis Leong; Anna Pomés; Kang Cheng; Andrew D. Howard; James Schaeffer; Reid J. Leonard

2000-01-01

253

Soluble Ecto-5?-nucleotidase (5?-NT), Alkaline Phosphatase, and Adenosine Deaminase (ADA1) Activities in Neonatal Blood Favor Elevated Extracellular Adenosine*  

PubMed Central

Extracellular adenosine, a key regulator of physiology and immune cell function that is found at elevated levels in neonatal blood, is generated by phosphohydrolysis of adenine nucleotides released from cells and catabolized by deamination to inosine. Generation of adenosine monophosphate (AMP) in blood is driven by cell-associated enzymes, whereas conversion of AMP to adenosine is largely mediated by soluble enzymes. The identities of the enzymes responsible for these activities in whole blood of neonates have been defined in this study and contrasted to adult blood. We demonstrate that soluble 5?-nucleotidase (5?-NT) and alkaline phosphatase (AP) mediate conversion of AMP to adenosine, whereas soluble adenosine deaminase (ADA) catabolizes adenosine to inosine. Newborn blood plasma demonstrates substantially higher adenosine-generating 5?-NT and AP activity and lower adenosine-metabolizing ADA activity than adult plasma. In addition to a role in soluble purine metabolism, abundant AP expressed on the surface of circulating neonatal neutrophils is the dominant AMPase on these cells. Plasma samples from infant observational cohorts reveal a relative plasma ADA deficiency at birth, followed by a gradual maturation of plasma ADA through infancy. The robust adenosine-generating capacity of neonates appears functionally relevant because supplementation with AMP inhibited whereas selective pharmacologic inhibition of 5?-NT enhanced Toll-like receptor-mediated TNF-? production in neonatal whole blood. Overall, we have characterized previously unrecognized age-dependent expression patterns of plasma purine-metabolizing enzymes that result in elevated plasma concentrations of anti-inflammatory adenosine in newborns. Targeted manipulation of purine-metabolizing enzymes may benefit this vulnerable population. PMID:23897810

Pettengill, Matthew; Robson, Simon; Tresenriter, Megan; Millan, Jose Luis; Usheva, Anny; Bingham, Taiese; Belderbos, Mirjam; Bergelson, Ilana; Burl, Sarah; Kampmann, Beate; Gelinas, Laura; Kollmann, Tobias; Bont, Louis; Levy, Ofer

2013-01-01

254

Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis  

SciTech Connect

The annotation of protein function is almost completely performed by in silico approaches. However, computational prediction of protein function is frequently incomplete and error prone. In Mycobacterium tuberculosis (Mtb), ~25% of all genes have no predicted function and are annotated as hypothetical proteins. This lack of functional information severely limits our understanding of Mtb pathogenicity. Current tools for experimental functional annotation are limited and often do not scale to entire protein families. Here, we report a generally applicable chemical biology platform to functionally annotate bacterial proteins by combining activity-based protein profiling (ABPP) and quantitative LC-MS-based proteomics. As an example of this approach for high-throughput protein functional validation and discovery, we experimentally annotate the families of ATP-binding proteins in Mtb. Our data experimentally validate prior in silico predictions of >250 ATPases and adenosine nucleotide-binding proteins, and reveal 73 hypothetical proteins as novel ATP-binding proteins. We identify adenosine cofactor interactions with many hypothetical proteins containing a diversity of unrelated sequences, providing a new and expanded view of adenosine nucleotide binding in Mtb. Furthermore, many of these hypothetical proteins are both unique to Mycobacteria and essential for infection, suggesting specialized functions in mycobacterial physiology and pathogenicity. Thus, we provide a generally applicable approach for high throughput protein function discovery and validation, and highlight several ways in which application of activity-based proteomics data can improve the quality of functional annotations to facilitate novel biological insights.

Ansong, Charles; Ortega, Corrie; Payne, Samuel H.; Haft, Daniel H.; Chauvigne-Hines, Lacie M.; Lewis, Michael P.; Ollodart, Anja R.; Purvine, Samuel O.; Shukla, Anil K.; Fortuin, Suereta; Smith, Richard D.; Adkins, Joshua N.; Grundner, Christoph; Wright, Aaron T.

2013-01-24

255

Adenosine induces growth-cone turning of sensory neurons  

PubMed Central

The formation of appropriate connections between neurons and their specific targets is an essential step during development and repair of the nervous system. Growth cones are located at the leading edges of the growing neurites and respond to environmental cues in order to be guided to their final targets. Directional information can be coded by concentration gradients of substrate-bound or diffusible-guidance molecules. Here we show that concentration gradients of adenosine stimulate growth cones of sensory neurons (dorsal root ganglia) from chicken embryos to turn towards the adenosine source. This response is mediated by adenosine receptors. The subsequent signal transduction process involves cAMP. It may be speculated that the in vivo function of this response is concerned with the formation or the repair and regeneration of the peripheral nervous system. Electronic supplementary material The online version of this article (doi:10.1007/s11302-008-9121-3) contains supplementary material, which is available to authorised users. PMID:18777107

Grau, Benjamin; Eilert, John-Christian; Munck, Sebastian

2008-01-01

256

Pathophysiological roles for purines: adenosine, caffeine and urate  

PubMed Central

The motor symptoms of Parkinson's disease (PD) are due primarily to the degeneration of the dopaminergic neurons in the nigrostriatal pathway. However, several other brain areas and neurotransmitters other than dopamine such as noradrenaline, 5-hydroxytryptamine and acetylcholine are affected in the disease. Moreover, adenosine because of the extensive interaction of its receptors with the dopaminergic system has been implicated in the in the pathophysiology of the disease. Based on the involvement of these nondopaminergic neurotransmitters in PD and the sometimes severe adverse effects that limit the mainstay use of dopamine-based antiparkinsonian treatments, recent assessments have called for a broadening of therapeutic options beyond the traditional dopaminergic drug arsenal. In this review we describe the interactions between dopamine and adenosine receptors that underpin the preclinical and clinical rationale for pursuing adenosine A2A receptor antagonists as symptomatic and potentially neuroprotective treatment of PD. The review will pay particular attention to recent results regarding specific A2A receptor-receptor interactions and recent findings identifying urate, the end product of purine metabolism, as a novel prognostic biomarker and candidate neuroprotectant in PD. PMID:20696321

Morelli, Micaela; Carta, Anna R; Kachroo, Anil; Schwarzschild, Michael A.

2011-01-01

257

Extracellular adenosine metabolism in immune cells in melanoma.  

PubMed

Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, which leads to a strong immunosuppression associated with a rapid tumor progression. Adenosine is considered as one of the main immunosuppressive factors in the tumor environment. It is produced via enzymatic hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 localized on cell surface. Using the ret transgenic mouse melanoma model that closely mimics human melanoma, we demonstrated an increased frequency of ectonucleotidase-positive myeloid-derived suppressor cells (MDSCs) in melanoma lesions and lymphoid organs. Furthermore, we observed that conventional CD4(+)FoxP3(-) and CD8(+) T cells infiltrating melanoma lesions of ret transgenic mice were distinctly enriched in the CD39(+)CD73(+) subpopulation that co-expressed also PD-1. Ectonucleotidase expression was also up-regulated in CD4(+) and CD8(+) T cells upon activation. In addition, these ectoenzymes were largely found to be expressed on memory T cell compartment (in particular, on effector memory cells). Our data suggest that extracellular adenosine produced by regulatory T cells (Tregs) and MDSCs can suppress T cell effector functions through paracrine signaling. Another mechanism involves its production also by effector T cells and an inhibition of their anti-tumor reactivity via autocrine signaling as a part of the negative feedback loop. This mode of adenosine signaling could be also used by Tregs and MDSCs to enhance their immunosuppressive activity. PMID:24756420

Umansky, Viktor; Shevchenko, Ivan; Bazhin, Alexandr V; Utikal, Jochen

2014-10-01

258

Bioluminescent assay for serum adenosine deaminase with immobilized bacterial luciferase.  

PubMed

We describe a bioluminescence method for measuring adenosine deaminase activity in serum. The method involves use of batchwise enzyme reaction containing adenosine, alpha-ketoglutarate, glutamic dehydrogenase and NADH. The resulting solution is injected to the continuous-flow bioluminescence system. In the system, a bacterial luciferase and NAD(P)H:FMN oxidoreductase are covalently co-immobilized on Sepharose 4B. Carrier solution (pH 6.8) for bioluminescence reaction contains FMN and decanal. The continuous-flow light-emitting system, in which the reactor (flow cell packed with immobilized enzyme) is placed in front of a photomultiplier tube inside a photon counter, is versatile and simple. Concentration and response are linearly related from 1.2 to 92.5 pmol per injection of ammonia. The precision of the method is satisfactory (coefficient of variation 3.9-6.8%). We validated the technique by comparing results with conventional assay method (UV method). Normal values for adenosine deaminase activity of serum ranged from 7.0 to 22.0 U/l in agreement with those obtained by other method. The Sepharose 4B-immobilized enzymes are stable for more than one year. This assay system could be used as a routine clinical laboratory test in the diagnosis of liver damage. PMID:2620450

Oda, K; Yoshida, S; Hirose, S; Takeda, T

1989-10-31

259

Activities and some properties of 5'-nucleotidase, adenosine kinase and adenosine deaminase in tissues from vertebrates and invertebrates in relation to the control of the concentration and the physiological role of adenosine.  

PubMed Central

1. The maximal activities of 5'-nucleotidase, adenosine kinase and adenosine deaminase together with the Km values for their respective substrates were measured in muscle, nervous tissue and liver from a large range of animals to provide information on the mechanism of control of adenosine concentration in the tissues. 2. Detailed evidence that the methods used were optimal for the extraction and assay of these enzymes has been deposited as Supplementary Publication SUP 50088 (16pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K.,from whom copies can be obtained on the terms indicated in Biochem. J. (1978), 169, 5. This evidence includes the effects of pH and temperature on the activities of the enzymes. 3. In many tissues, the activities of 5'-nucleotidase were considerably higher than the sum of the activities of adenosine kinase and deaminase, which suggests that the activity of the nucleotidase must be markedly inhibited in vivo so that adenosine does not accumulate. In the tissues in which comparison is possible, the Km of the nucleotidase is higher than the AMP content of the tissue, and since some of the latter may be bound within the cell, the low concentration of substrate may, in part, be responsible for a low activity in vivo. 4. In most tissues and animals investigated, the values of the Km of adenosine kinase for adenosine are between one and two orders of magnitude lower than those for the deaminase. It is suggested that 5'-nucleotidase and adenosine kinase are simultaneously active so that a substrate cycle between AMP and adenosine is produced: the difference in Km values between kinase and deaminase indicates that, via the cycle, small changes in activity of kinase or nucleotidase produce large changes in adenosine concentration. 5. The activities of adenosine kinase or deaminase from vertebrate muscles are inversely correlated with the activities of phosphorylase in these muscles. Since the magnitude of the latter activities are indicative of the anaerobic nature of muscles, this negative correlation supports the hypothesis that an important role of adenosine is the regulation of blood flow in the aerobic muscles. PMID:215126

Arch, J R; Newsholme, E A

1978-01-01

260

Modulatory Effects of Endogenous Adenosine on Epinephrine Secretion From the Adrenal Medulla of the Rat  

Microsoft Academic Search

Abstract The purpose of this study was to examine (1) whether endogenous,adenosine receptors inhibit the release of epineph- rine and norepinephrine,from adrenal medulla in response to physiological and pharmacological,stimuli and (2) whether,the renin-angiotensin system modulates,this effect of endogenous adenosine. We used a conscious animal model,to approximate normal physiological conditions. Male Sprague-Dawley rats were treated with a surface adenosine receptor antagonist,

Ching-jiunn Tseng; Wen-yu Ho; Hui-ching Lin; Che-se Tung; Chia-jen Kuan

261

Roles of adenosine and its receptors in sleep-wake regulation.  

PubMed

This chapter summarizes the current knowledge about the role of adenosine in the sleep-wake regulation with a focus on adenosine in the brain, regulation of adenosine levels, adenosine receptors, and manipulations of the adenosine system by the use of pharmacological and molecular biological tools. Adenosine is neither stored nor released as a classical neurotransmitter and is thought to be formed inside cells or on their surface, mostly by breakdown of adenine nucleotides. The extracellular level of adenosine increases in the cortex and basal forebrain (BF) during prolonged wakefulness and decreases during the sleep-recovery period. Therefore, adenosine is proposed to act as a homeostatic regulator of sleep. The endogenous somnogen prostaglandin (PG) D2 increases the extracellular level of adenosine under the subarachnoid space of the BF and promotes physiological sleep. There are four adenosine receptor subtypes: adenosine A1 receptor (R, A1R), A2AR, A2BR, and A3R. Both the A1R and the A2AR have been reported to be involved in sleep induction. The A2AR plays an important role in the somnogenic effects of PGD2. Activation of A2AR by its agonist infused into the brain potently increases sleep and the arousal effect of caffeine, an A1R and A2AR antagonist, was shown to be dependent on the A2AR. On the other hand, inhibition of wake-promoting neurons via the A1R also mediates the sleep-inducing effects of adenosine, whereas activation of A1R in the lateral preoptic area induces wakefulness. These findings indicate that A2AR plays a predominant role in sleep induction, whereas A1R regulates the sleep-wake cycle in a site-dependent manner. PMID:25175972

Huang, Zhi-Li; Zhang, Ze; Qu, Wei-Min

2014-01-01

262

John Montgomery's Legacy: Carbocyclic Adenosine Analogues as Sah Hydrolase Inhibitors with Broad-Spectrum Antiviral Activity  

Microsoft Academic Search

Ever since the S-adenosylhomocysteine (AdoHcy, SAH) hydrolase was recognized as a pharmacological target for antiviral agents (J. A. Montgomery et al., J. Med. Chem. 25:626–629, 1982), an increasing number of adenosine, acyclic adenosine, and carbocyclic adenosine analogues have been described as potent SAH hydrolase inhibitors endowed with broad-spectrum antiviral activity. The antiviral activity spectrum of the SAH hydrolase inhibitors include

E. De Clercq

2005-01-01

263

Adenosine regulates the IL1beta-induced cellular functions of human gingival fibroblasts  

Microsoft Academic Search

In this study we examined the influence of adenosine on the cellular functions of human gingival fibroblasts (HGF), such as the production of inflammatory cytokines and extracellular matrices (ECM), and the expression and function of adhesion molecules. Concerning the expression of adenosine receptors, RT-PCR analysis revealed that HGF expressed adenosine receptor A1, A2a and A2b, but not A3 mRNA. Ligation

Shinya Murakami; Tomoko Hashikawa; Teruyuki Saho; Masahide Takedachi; Takenori Nozaki; Yoshio Shimabukuro; Hiroshi Okada

2001-01-01

264

S-Adenosylhomocysteine hydrolase as a target for intracellular adenosine action  

Microsoft Academic Search

S-Adenosylhomocysteine hydrolase (AdoHcyase) controls intracellular levels of S-adenosylhomocysteine (AdoHcy). AdoHcy is a potent product inhibitor of some S-adenosylmethionine-dependent methyltransferases. Pharmacological modulation of AdoHcyase to indirectly inhibit methyltransferases can be guided by the fact that adenosine binds with high affinity to AdoHcyase and inhibits enzyme activity. cAMP can compete with adenosine and can counteract the adenosine-induced inhibition of AdoHcyase. Thus, the

Doris Kloor; Hartmut Osswald

2004-01-01

265

Adenosine A 1 receptor agonism in the immature rat brain and heart  

Microsoft Academic Search

We examined if the adenosine A1 receptor agonist adenosine amine congener (ADAC, 100 ?g\\/kg i.p.) is neuroprotective in 7-day-old rats subjected to hypoxic ischemia. Brain damage, evaluated as weight deficit and gross morphology, was not affected by ADAC treatment. Nonetheless, ADAC (100 ?g\\/kg i.p.) reduced heart rate by 44% (p<0.0001), indicating that the dose given was pharmacologically active. Adenosine A1

Ulrika Ådén; Anna-Lena Leverin; Henrik Hagberg; Bertil B Fredholm

2001-01-01

266

Mechanisms involved in the adenosine-induced vasorelaxation to the pig prostatic small arteries  

Microsoft Academic Search

Benign prostatic hypertrophy has been related with glandular ischemia processes and adenosine is a potent vasodilator agent.\\u000a This study investigates the mechanisms underlying the adenosine-induced vasorelaxation in pig prostatic small arteries. Adenosine\\u000a receptors expression was determined by Western blot and immunohistochemistry, and rings were mounted in myographs for isometric\\u000a force recording. A2A and A3 receptor expression was observed in the

Ana S. F. Ribeiro; Vítor S. Fernandes; Luis M. Orensanz; María Pilar Martínez; Paz Recio; Ana Martínez-Sáenz; Belén Climent; Jose Luis Arteaga; Albino García-Sacristán; Dolores Prieto; Medardo Hernández

267

Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture  

Microsoft Academic Search

Acupuncture is an invasive procedure commonly used to relieve pain. Acupuncture is practiced worldwide, despite difficulties in reconciling its principles with evidence-based medicine. We found that adenosine, a neuromodulator with anti-nociceptive properties, was released during acupuncture in mice and that its anti-nociceptive actions required adenosine A1 receptor expression. Direct injection of an adenosine A1 receptor agonist replicated the analgesic effect

Nanna Goldman; Michael Chen; Takumi Fujita; Qiwu Xu; Weiguo Peng; Wei Liu; Tina K Jensen; Yong Pei; Fushun Wang; Xiaoning Han; Jiang-Fan Chen; Jurgen Schnermann; Takahiro Takano; Kim Tieu; Maiken Nedergaard

2010-01-01

268

Changes in Myocardial A1 Adenosine Receptor and Message Levels during Fetal Development and Postnatal Maturation  

Microsoft Academic Search

Previously we have shown myocardial adenosine A1 receptors are up-regulated during the newborn period. The timing of the increase or the mechanism of the changes are not known. The purpose of the present study was to (1) determine the time course of increased A1 adenosine receptors during fetal development and (2) determine if A1 adenosine receptor regulation is secondary to

Paul Matherne; Anne M. Byford; Joan T. Gilrain; Alan C. Dalkin

1996-01-01

269

Intracoronary Adenosine versus Intravenous Adenosine during Primary PCI for ST-Elevation Myocardial Infarction: Which One Offers Better Outcomes in terms of Microvascular Obstruction?  

PubMed Central

Aims. Previous studies have suggested that intravenous administration of adenosine improves myocardial reperfusion and reduces infarct size in ST-elevation myocardial infarction (STEMI) patients. Intracoronary administration of adenosine has shown conflicting results. Methods. In this retrospective, single-centre, blinded clinical study, we assessed whether selective intracoronary administration of adenosine distal to the occlusion site immediately before initial balloon inflation reduces microvascular obstruction (MVO) as assessed with cardiac magnetic resonance imaging (MRI). Using contrast-enhanced sequences, microvascular obstruction (MVO) was calculated. We found 81 patients presenting with STEMI within 12?h from symptom onset who were eligible for the study. In 80/81 (100%) patients receiving the study drug, MRI was performed on Day 1 after primary angioplasty. Results. The prevalence of MVO was reduced in the patients treated with intracoronary adenosine, (45%) compared to 85% of patients who were administered intravenous adenosine (P = 0.0043). We found that the size of MVO in patients receiving intracoronary adenosine was significantly reduced compared to 0.91?g in the intravenous-treated group (P = 0.027). There was no statistically significant difference in TIMI flow and clinical outcomes after primary PCI. Conclusion. We found significant evidence that selective high-dose intracoronary administration of adenosine distal to the occlusion site of the culprit lesion in STEMI patients results in a decrease in microvascular obstruction. PMID:23606984

Doolub, Gemina; Dall'Armellina, Erica

2013-01-01

270

Activity-dependent adenosine release may be linked to activation of Na(+)-K(+) ATPase: an in vitro rat study.  

PubMed

In the brain, extracellular adenosine increases as a result of neuronal activity. The mechanisms by which this occurs are only incompletely understood. Here we investigate the hypothesis that the Na(+) influxes associated with neuronal signalling activate the Na(+)-K(+) ATPase which, by consuming ATP, generates intracellular adenosine that is then released via transporters. By measuring adenosine release directly with microelectrode biosensors, we have demonstrated that AMPA-receptor evoked adenosine release in basal forebrain and cortex depends on extracellular Na(+). We have simultaneously imaged intracellular Na(+) and measured adenosine release. The accumulation of intracellular Na(+) during AMPA receptor activation preceded adenosine release by some 90 s. By removing extracellular Ca(2+), and thus preventing indiscriminate neuronal activation, we used ouabain to test the role of the Na(+)-K(+) ATPase in the release of adenosine. Under conditions which caused a Na(+) influx, brief applications of ouabain increased the accumulation of intracellular Na(+) but conversely rapidly reduced extracellular adenosine levels. In addition, ouabain greatly reduced the amount of adenosine released during application of AMPA. Our data therefore suggest that activity of the Na(+)-K(+) ATPase is directly linked to the efflux of adenosine and could provide a universal mechanism that couples adenosine release to neuronal activity. The Na(+)-K(+) ATPase-dependent adenosine efflux is likely to provide adenosine-mediated activity-dependent negative feedback that will be important in many diverse functional contexts including the regulation of sleep. PMID:24489921

Sims, Robert Edward; Dale, Nicholas

2014-01-01

271

Activity-Dependent Adenosine Release May Be Linked to Activation of Na+-K+ ATPase: An In Vitro Rat Study  

PubMed Central

In the brain, extracellular adenosine increases as a result of neuronal activity. The mechanisms by which this occurs are only incompletely understood. Here we investigate the hypothesis that the Na+ influxes associated with neuronal signalling activate the Na+-K+ ATPase which, by consuming ATP, generates intracellular adenosine that is then released via transporters. By measuring adenosine release directly with microelectrode biosensors, we have demonstrated that AMPA-receptor evoked adenosine release in basal forebrain and cortex depends on extracellular Na+. We have simultaneously imaged intracellular Na+ and measured adenosine release. The accumulation of intracellular Na+ during AMPA receptor activation preceded adenosine release by some 90 s. By removing extracellular Ca2+, and thus preventing indiscriminate neuronal activation, we used ouabain to test the role of the Na+-K+ ATPase in the release of adenosine. Under conditions which caused a Na+ influx, brief applications of ouabain increased the accumulation of intracellular Na+ but conversely rapidly reduced extracellular adenosine levels. In addition, ouabain greatly reduced the amount of adenosine released during application of AMPA. Our data therefore suggest that activity of the Na+-K+ ATPase is directly linked to the efflux of adenosine and could provide a universal mechanism that couples adenosine release to neuronal activity. The Na+-K+ ATPase-dependent adenosine efflux is likely to provide adenosine-mediated activity-dependent negative feedback that will be important in many diverse functional contexts including the regulation of sleep. PMID:24489921

Sims, Robert Edward; Dale, Nicholas

2014-01-01

272

Characterization of Spontaneous, Transient Adenosine Release in the Caudate-Putamen and Prefrontal Cortex  

PubMed Central

Adenosine is a neuroprotective agent that inhibits neuronal activity and modulates neurotransmission. Previous research has shown adenosine gradually accumulates during pathologies such as stroke and regulates neurotransmission on the minute-to-hour time scale. Our lab developed a method using carbon-fiber microelectrodes to directly measure adenosine changes on a sub-second time scale with fast-scan cyclic voltammetry (FSCV). Recently, adenosine release lasting a couple of seconds has been found in murine spinal cord slices. In this study, we characterized spontaneous, transient adenosine release in vivo, in the caudate-putamen and prefrontal cortex of anesthetized rats. The average concentration of adenosine release was 0.17±0.01 µM in the caudate and 0.19±0.01 µM in the prefrontal cortex, although the range was large, from 0.04 to 3.2 µM. The average duration of spontaneous adenosine release was 2.9±0.1 seconds and 2.8±0.1 seconds in the caudate and prefrontal cortex, respectively. The concentration and number of transients detected do not change over a four hour period, suggesting spontaneous events are not caused by electrode implantation. The frequency of adenosine transients was higher in the prefrontal cortex than the caudate-putamen and was modulated by A1 receptors. The A1 antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine, 6 mg/kg i.p.) increased the frequency of spontaneous adenosine release, while the A1 agonist CPA (N6-cyclopentyladenosine, 1 mg/kg i.p.) decreased the frequency. These findings are a paradigm shift for understanding the time course of adenosine signaling, demonstrating that there is a rapid mode of adenosine signaling that could cause transient, local neuromodulation. PMID:24494035

Nguyen, Michael D.; Lee, Scott T.; Ross, Ashley E.; Ryals, Matthew; Choudhry, Vishesh I.; Venton, B. Jill

2014-01-01

273

Adenosine Inhibits the Excitatory Synaptic Inputs to Basal Forebrain Cholinergic, GABAergic, and Parvalbumin Neurons in Mice  

PubMed Central

Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal forebrain (BF) region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV) neurons to determine the effect of adenosine. Whole-cell recordings were made from BF cholinergic neurons and from BF GABAergic and PV neurons with the size (>20??m) and intrinsic membrane properties (prominent H-currents) corresponding to cortically projecting neurons. A brief (2?min) bath application of adenosine (100??M) decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in all groups of BF cholinergic, GABAergic, and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1??M). Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1 receptor-mediated inhibition of glutamatergic inputs to cortically projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required for attention and cognition. PMID:23801984

Yang, Chun; Franciosi, Serena; Brown, Ritchie E.

2013-01-01

274

Adenosine signaling contributes to ethanol-induced fatty liver in mice  

PubMed Central

Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the biochemical and pharmacological mechanisms by which ethanol stimulates these molecular changes remain unknown. During ethanol metabolism, adenosine is generated by the enzyme ecto-5?-nucleotidase, and adenosine production and adenosine receptor activation are known to play critical roles in the development of hepatic fibrosis. We therefore investigated whether adenosine and its receptors play a role in the development of alcohol-induced fatty liver. WT mice fed ethanol on the Lieber-DeCarli diet developed hepatic steatosis, including increased hepatic triglyceride content, while mice lacking ecto-5?-nucleotidase or adenosine A1 or A2B receptors were protected from developing fatty liver. Similar protection was also seen in WT mice treated with either an adenosine A1 or A2B receptor antagonist. Steatotic livers demonstrated increased expression of genes involved in fatty acid synthesis, which was prevented by blockade of adenosine A1 receptors, and decreased expression of genes involved in fatty acid metabolism, which was prevented by blockade of adenosine A2B receptors. In vitro studies supported roles for adenosine A1 receptors in promoting fatty acid synthesis and for A2B receptors in decreasing fatty acid metabolism. These results indicate that adenosine generated by ethanol metabolism plays an important role in ethanol-induced hepatic steatosis via both A1 and A2B receptors and suggest that targeting adenosine receptors may be effective in the prevention of alcohol-induced fatty liver. PMID:19221436

Peng, Zhongsheng; Borea, Pier Andrea; Wilder, Tuere; Yee, Herman; Chiriboga, Luis; Blackburn, Michael R.; Azzena, Gianfranco; Resta, Giuseppe; Cronstein, Bruce N.

2009-01-01

275

Regulation of Arousal by Adenosine A1 and A2A Receptors in the Prefrontal Cortex of C57BL/6J Mouse.  

E-print Network

??Adenosine levels in the basal forebrain and cortex increase with prolonged wakefulness to promote sleep. Caffeine increases wakefulness by blocking adenosine receptors, yet the neurotransmitter… (more)

Van Dort, Christa J.

2008-01-01

276

Adenosine analogue inhibitors of S-adenosylhomocysteine hydrolase.  

PubMed

Elevated plasma homocysteine (Hcy) levels are an independent risk factor for the onset and progression of Alzheimer's disease. Reduction of Hcy to normal levels therefore presents a new approach for disease modification. Hcy is produced by the cytosolic enzyme S-adenosylhomocysteine hydrolase (AHCY), which converts S-adenosylhomocysteine (SAH) to Hcy and adenosine. Herein we describe the design and characterization of novel, substrate-based S-adenosylhomocysteine hydrolase inhibitors with low nanomolar potency in vitro and robust activity in vivo. PMID:24813734

Converso, Antonella; Hartingh, Timothy; Fraley, Mark E; Garbaccio, Robert M; Hartman, George D; Huang, Shaei Y; Majercak, John M; McCampbell, Alexander; Na, Sang Jin; Ray, William J; Savage, Mary J; Wolffe, Carrie; Yeh, Suzie; Yu, Yuanjiang; White, Rebecca; Zhang, Rena

2014-06-15

277

Inhibitory effects of black soybean on platelet activation mediated through its active component of adenosine.  

PubMed

Owing to the beneficial health effects on human cardiovascular system, soybeans and soy-related products have been a focus of intensive research. Soy isoflavones are known to be primarily responsible for the soy-related biological effects including anti-platelet activity but its in vivo relevancy has not been fully verified. Here we compared the role of adenosine, an active ingredient abundant in black soybean (BB) extract, in the anti-platelet effects of BB, to that of soy isoflavones. At the concentrations existing in BB, isoflavones such as genistein and daidzein could not attenuate collagen-induced platelet aggregation, however, adenosine significantly inhibited platelet aggregation with an equivalent potency to BB, suggesting that adenosine may be the major bioactive component. Consistently, the anti-aggregatory effects of BB disappeared after treatment of adenosine receptor antagonists. The effects of BB are mediated by adenosine through intracellular cAMP and subsequent attenuation of calcium mobilization. Of note, adenosine and BB significantly reduced platelet fibrinogen binding and platelet adhesion, other critical events for platelet activation, which were not affected by isoflavones. Taken together, we demonstrated that adenosine might be the major active ingredient for BB-induced anti-platelet activity, which will shed new light on the roles of adenosine as a bioactive compound in soybeans and soy-related food. PMID:23332980

Kim, Keunyoung; Lim, Kyung-Min; Shin, Hyun-Jung; Seo, Dae-Bang; Noh, Ji-Yoon; Kang, Seojin; Chung, Han Young; Shin, Sue; Chung, Jin-Ho; Bae, Ok-Nam

2013-03-01

278

Photomodulation of g protein-coupled adenosine receptors by a novel light-switchable ligand.  

PubMed

The adenosinergic system operates through G protein-coupled adenosine receptors, which have become promising therapeutic targets for a wide range of pathological conditions. However, the ubiquity of adenosine receptors and the eventual lack of selectivity of adenosine-based drugs have frequently diminished their therapeutic potential. Accordingly, here we aimed to develop a new generation of light-switchable adenosine receptor ligands that change their intrinsic activity upon irradiation, thus allowing the spatiotemporal control of receptor functioning (i.e., receptor activation/inactivation dependent on location and timing). Therefore, we synthesized an orthosteric, photoisomerizable, and nonselective adenosine receptor agonist, nucleoside derivative MRS5543 containing an aryl diazo linkage on the N(6) substituent, which in the dark (relaxed isomer) behaved as a full adenosine A3 receptor (A3R) and partial adenosine A2A receptor (A2AR) agonist. Conversely, upon photoisomerization with blue light (460 nm), it remained a full A3R agonist but became an A2AR antagonist. Interestingly, molecular modeling suggested that structural differences encountered within the third extracellular loop of each receptor could modulate the intrinsic, receptor subtype-dependent, activity. Overall, the development of adenosine receptor ligands with photoswitchable activity expands the pharmacological toolbox in support of research and possibly opens new pharmacotherapeutic opportunities. PMID:25248077

Bahamonde, María Isabel; Taura, Jaume; Paoletta, Silvia; Gakh, Andrei A; Chakraborty, Saibal; Hernando, Jordi; Fernández-Dueñas, Víctor; Jacobson, Kenneth A; Gorostiza, Pau; Ciruela, Francisco

2014-10-15

279

Adenosine Diphosphate Effect on Contractility of Human Muscle Actomyosin: Inhibition by Ethanol and Acetaldehyde  

Microsoft Academic Search

Magnesium adenosine triphosphate (Mg2+-ATP) is known to produce dissociation of muscle actin and myosin in vitro, while its hydrolysis leads to reassociation. The interaction of purified actin and myosin from human muscle, in the presence of Mg2+-ATP. was stimulated by minute amounts of adenosine diphosphate (ADP), a product of ATP hydrolysis. By contrast, the dissociation of the actomyosin complex was

Saul Puszkin; Emanuel Rubin

1975-01-01

280

Adenosine and glutamate in neuroglial interaction: implications for circadian disorders and alcoholism.  

PubMed

Recent studies have demonstrated that the function of glia is not restricted to the support of neuronal function. In fact, astrocytes are essential for neuronal activity in the brain and play an important role in the regulation of complex behavior. Astrocytes actively participate in synapse formation and brain information processing by releasing and uptaking glutamate, D-serine, adenosine 5'-triphosphate (ATP), and adenosine. In the central nervous system, adenosine-mediated neuronal activity modulates the actions of other neurotransmitter systems. Adenosinergic fine-tuning of the glutamate system in particular has been shown to regulate circadian rhythmicity and sleep, as well as alcohol-related behavior and drinking. Adenosine gates both photic (light-induced) glutamatergic and nonphotic (alerting) input to the circadian clock located in the suprachiasmatic nucleus of the hypothalamus. Astrocytic, SNARE-mediated ATP release provides the extracellular adenosine that drives homeostatic sleep. Acute ethanol increases extracellular adenosine, which mediates the ataxic and hypnotic/sedative effects of alcohol, while chronic ethanol leads to downregulated adenosine signaling that underlies insomnia, a major predictor of relapse. Studies using mice lacking the equilibrative nucleoside transporter 1 have illuminated how adenosine functions through neuroglial interactions involving glutamate uptake transporter GLT-1 [referred to as excitatory amino acid transporter 2 (EAAT2) in human] and possibly water channel aquaporin 4 to regulate ethanol sensitivity, reward-related motivational processes, and alcohol intake. PMID:25236726

Ruby, Christina L; O'Connor, Katheryn M; Ayers-Ringler, Jennifer; Choi, Doo-Sup

2014-01-01

281

Monoclonal antibodies to adenosine receptor by an auto-anti-idiotypic approach  

SciTech Connect

BALB/c mice were immunized with adenosine 6-aminocaproyl-BSA. Hybridoma cell lines that secreted anti-idiotypic antibodies were identified by their binding to rabbit anti-adenosine antibodies, but not to normal rabbit immunoglobulins. Two such monoclonal antibodies, AA18 and AA21, also inhibited the binding of ({sup 3}H)adenosine to the rabbit anti-adenosine antibodies. Therefore, both appeared to recognize idiotypic determinants on the rabbit anti-adenosine antibodies. The monoclonal antibodies AA18 and AA21 were established as being directed at adenosine receptors by the following criteria: (1) they bound to both rat and bovine brain membranes, and binding could be inhibited by CHA, an adenosine receptor agonist, (2) they inhibited the binding of ({sup 3}H)R-PIA, an adenosine receptor agonist, to rat brain membranes; and (3) they inhibited the adenylate cyclase of rat brain membranes. The monoclonal antibodies were used to screen cDNA libraries in lambda gt11.

Ku, Hsing-Hsu.

1988-01-01

282

Modulation of Hippocampal Glutamatergic Transmission by ATP Is Dependent on Adenosine A1 Receptors  

Microsoft Academic Search

Excitatory glutamatergic synapses in the hippocampal CA1 region of rats are potently inhibited by purines, including aden- osine, ATP, and ATP analogs. Adenosine A1 receptors are known to mediate at least part of the response to adenine nucleotides, either because adenine nucleotides activate A1 receptors directly, or activate them secondarily upon the nu- cleotides' conversion to adenosine. In the present

SUSAN A. MASINO; LIHONG DIAO; PETER ILLES; NANCY R. ZAHNISER; GAYNOR A. LARSON; ORN JOHANSSON; BERTIL B. FREDHOLM; THOMAS V. DUNWIDDIE

2002-01-01

283

Increase of adenosine content in cerebral cortex of the cat during bicuculline-induced seizure  

Microsoft Academic Search

In order to elucidate whether adenosine may be involved in the increase in cerebral blood flow (CBF) during functional hyperemia, cortical tissue levels of adenosine, inosine and hypoxanthine were measured in the cat following bicuculline (3 mg\\/kg)-induced seizure. In addition, the subcellular distribution of 5'-nucleotidase in the cortex was determined by histochemical techniques. Experiments were performed on anaesthetized and immobilized

J. Schrader; M. Wahl; W. Kuschinsky; G. W. Kreutzberg

1980-01-01

284

A model of dual circulation in liver acini with hypoxia regulated adenosine secretion  

Microsoft Academic Search

It was postulated by W.W. Lautt that the hepatic artery flow compensation for changes in portal vein flow (the ‘hepatic arterial buffer response’) is regulated through the portal blood washout of adenosine from the small fluid compartment that surrounds the hepatic arterial resistance vessels. It is presumed that the adenosine secretion there is constant and independent of oxygen supply or

Sven Kurbel; Beatrica Kurbel; Aleksandar V?ev; Branka Lon?ar; Vesna Vegar-Brozovi?; Josip ?av?i?

2003-01-01

285

Spreading depolarization-induced adenosine accumulation reflects metabolic status in vitro and in vivo.  

PubMed

Spreading depolarization (SD), a pathologic feature of migraine, stroke and traumatic brain injury, is a propagating depolarization of neurons and glia causing profound metabolic demand. Adenosine, the low-energy metabolite of ATP, has been shown to be elevated after SD in brain slices and under conditions likely to trigger SD in vivo. The relationship between metabolic status and adenosine accumulation after SD was tested here, in brain slices and in vivo. In brain slices, metabolic impairment (assessed by nicotinamide adenine dinucleotide (phosphate) autofluorescence and O2 availability) was associated with prolonged extracellular direct current (DC) shifts indicating delayed repolarization, and increased adenosine accumulation. In vivo, adenosine accumulation was observed after SD even in otherwise healthy mice. As in brain slices, in vivo adenosine accumulation correlated with DC shift duration and increased when DC shifts were prolonged by metabolic impairment (i.e., hypoglycemia or middle cerebral artery occlusion). A striking pattern of adenosine dynamics was observed during focal ischemic stroke, with nearly all the observed adenosine signals in the periinfarct region occurring in association with SDs. These findings suggest that adenosine accumulation could serve as a biomarker of SD incidence and severity, in a range of clinical conditions. PMID:25160669

Lindquist, Britta E; Shuttleworth, C William

2014-11-01

286

Ab initio study of the reaction mechanism of ribonuclease A with cytidyl-3',5'-adenosine. I. Geometry optimization of cytidyl-3', 5'-adenosine.  

PubMed

As a first part of the ab initio study of the reaction mechanism of ribonuclease A with cytidyl-3',5'-adenosine, the geometry of the cytidyl-3',5'-adenosine substrate has been optimized using the Hartree-Fock method. Eleven different starting structures of cytidyl-3',5'-adenosine have been studied. To guarantee a proper alignment with the active site of the ribonuclease A enzyme, a part of the substrate was fixed during the geometry optimization. The geometry and intramolecular interactions of the refined conformations have been evaluated and two possible prototype structures have been proposed. One of these prototypes is more in accordance with the results of a molecular dynamics simulation and is therefore presented as a model for the geometry of cytidyl-3', 5'-adenosine in the initial step of the reaction with ribonuclease A. PMID:10547525

Peeters, A; Van Alsenoy, C

1999-12-01

287

Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: Role of purine release in ischemic and reperfusion injury  

Microsoft Academic Search

In a previous report, we have demonstrated that simultaneous inhibition of nucleoside transport and adenosine deaminase accumulates endogenous adenosine and protects the myocardium against stunning. The differential cardioprotective effects of erythro-9(2-hydroxy-3-nonyl)-adenine (EHNA), a potent inhibitor of adenosine deamination but not transport, and p-nitrobenzylthioinosine (NBMPR), a selective blocker of adenosine and inosine transport, are not known.

Anwar S. Abd-Elfattah; Michael E. Jessen; Jon Lekven; Andrew S. Wechsler

1998-01-01

288

Transducing system operated by adenosine A 2A receptors to facilitate acetylcholine release in the rat hippocampus  

Microsoft Academic Search

Although molecular biology studies indicate the presence of adenosine A2A receptors in the rat hippocampus, the pharmacological characterization of adenosine A2A receptor binding and of its putative facilitatory effects has revealed features essentially different from these found for adenosine A2A receptors in most preparations. We now confirmed that activation of adenosine A2A receptors with 2-[4-(2-p-carboxyethyl)phenylamino]-5?-N-ethylcarboxamidoadenosine (CGS 21680, 1-30 nM) or

Nelson Rebola; Catarina R. Oliveira; Rodrigo A. Cunha

2002-01-01

289

An Adenosine Analogue, IB-MECA, Down-Regulates Estrogen Receptor and Suppresses Human Breast Cancer Cell Proliferation1  

Microsoft Academic Search

Adenosine, a natural metabolite, plays important roles in several physiological and pathological processes, including modulation of cel- lular proliferation. Here, we report that among different adenosine analogues tested, micromolar concentrations of the A3 adenosine receptor (A3AR)-selective agonist N 6 -(3-iodobenzyl)adenosine-5-N- methyluronamide (IB-MECA) completely inhibited the growth of the human breast cancer cell lines MCF-7 and ZR-75 while inducing apoptosis in

Jun Lu; Anne Pierron; Katya Ravid

2003-01-01

290

Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists: Effect of the N-5 bond type on the affinity and selectivity at the four adenosine receptor subtypes  

Microsoft Academic Search

In the last few years, many efforts have been made to search for potent and selective human A3 adenosine antagonists. In particular, one of the most promising human A3 adenosine receptor antagonists is represented by the pyrazolo-triazolo-pyrimidine family. This class of compounds has been\\u000a strongly investigated from the point of view of structure-activity relationships. In particular, it has been observed

Chiara Bolcato; Claudia Cusan; Giorgia Pastorin; Giampiero Spalluto; Barbara Cacciari; Karl Norbert Klotz; Erika Morizzo; Stefano Moro

2008-01-01

291

On-Pump Inhibition of the es-ENT1 Nucleoside Transporter and Adenosine Deaminase during Aortic Cross-Clamping Entraps Intracellular Adenosine and Protects against Reperfusion Injury  

PubMed Central

Objectives Inhibition of adenosine deaminase, with EHNA (erythro-9 (2-hydroxy-3-nonyl)-adenine), and the es-ENT1 transporter, with NBMPR (p-nitro- benzylthioinosine), entraps myocardial intracellular adenosine during on pump warm cross clamping (ACC) leading to a complete recovery of cardiac function and ATP during reperfusion. The differential role of entrapped intracellular and circulating adenosine in EHNA/NBMPR-mediated protection is unknown. Selective, DPCPX [8-cyclopentyl-1,3-dipropyl-xanthine], or non-selective, [8-(p-sulfophenyltheophyline], A1-receptor antagonists were used to block adenosine A1-receptor contribution in EHNA/NBMPR-mediated cardiac recovery. Methods Anesthetized dogs (n= 45), instrumented to measure heart performance using sonomicrometry, were subjected to 30 minutes of warm ACC and 60 minutes of reperfusion. Three boluses of the vehicle (Series A) or 100?M EHNA and 25?M NBMPR (Series B) were infused into the pump at baseline, before ischemia and before reperfusion. DPCPX (10 ?M) or 8-SPT (100?M) was intra-aortically infused immediately after ACC distal to the clamp in Series (A) and Series (B). ATP pool and NAD+ was determined using HPLC. Results Ischemia depleted ATP in all groups by 50%. The ratios between adenosine to inosine were >10 fold higher in Series (B) than in Series (A) (p<0.001). ATP and function recovered in the EHNA/NBMPR-treated group (p<0.05 vs. control group). DPCPX or 8-SPT partially reduced cardiac function in Series (A) and (B) to the same degree but did not abolish EHNA/NBMPR-mediated protection in Series (B). Conclusion In addition to cardioprotection mediated by activation of adenosine receptors by extracellular adenosine, EHNA/NBMPR-entrapment of intracellular adenosine provides a significant component of myocardial protection despite of A1-R blockade. PMID:22325325

Abd-Elfattah, Anwar Saad; Ding, Mai; Jessen, Michael E.; Wechsler, Andrew S.

2012-01-01

292

Modulation of protein kinase C by adenosine: Involvement of adenosine A 1 receptor-pertussis toxin sensitive nucleotide binding protein system  

Microsoft Academic Search

The objective of this study was to determine whether adenosine A1 or A2 receptor was responsible for the regulation of protein kinase C (PKC) in porcine coronary artery and its coupling to G-protein. Endothelium denuded arterial rings were incubated with PDBu (200nM) in the presence or absence of adenosine receptor agonists and antagonists for 1 day. Following incubation, the arterial

Ravi B. Marala; S. Jamal Mustafa

1995-01-01

293

Noncovalent Interaction of Uridine 5?Monophosphate with Adenosine, Cytidine, and Thymidine, as well as Adenosine 5?Monophosphate and Cytidine 5?Monophosphate in Aqueous Solution  

Microsoft Academic Search

Adduct formation has been studied in the systems of uridine 5?-monophosphate (UMP) with adenosine (Ado), cytidine (Cyd), thymidine (Thd), adenosine 5?-monophosphate (AMP), and cytidine 5?-monophosphate (CMP) by the potentiometric method with computer analysis of the data and 13C and 31P NMR spectroscopic measurements. It has been established that in the complexes identified, ion–dipole and dipole–dipole interactions\\u000a occur with the positive

Lechoslaw Lomozik; Renata Jastrzab

2006-01-01

294

Synchrotron-excited time-resolved fluorescence spectroscopy of adenosine, protonated adenosine and 6 N, 6 N-dimethyladenosine in aqueous solution at room temperature  

Microsoft Academic Search

The fluorescence behavior of adenosine in neutral solution has been studied by time-resolved spectroscopy using synchrotron excitation and timecorrelated single photon counting, and by decay time measurements. Three emissions have been identified and correlated with three excitation spectra. The assignment of these transitions has been made by comparison with similar measurements on 6N, 6N-dimethyladenosine (6 DMA), and on adenosine in

J.-P. Ballini; M. Daniels; P. Vigny

1988-01-01

295

Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies.  

PubMed

Over the last decade, adenosine receptors in the central nervous system have been implicated in the modulation of cognitive functions. Despite the general view that endogenous adenosine modulates cognition through the activation of adenosine A1 receptors, evidence is now emerging on a possible role of A2A receptors in learning and memory. The present review attempts to examine results reported in different studies using diverse animal models, to provide a comprehensive picture of the recent evidence of a relationship between adenosinergic function and memory deficits. The present data suggest that caffeine (a nonselective adenosine receptor antagonist) and selective adenosine A2A receptor antagonists can improve memory performance in rodents evaluated through different tasks. They might also afford protection against memory dysfunction elicited in experimental models of aging, Alzheimer's disease, Parkinson's disease and, in spontaneously hypertensive rats (SHR), a putative genetic model of attention deficit hyperactivity disorder (ADHD). PMID:17981738

Takahashi, Reinaldo Naoto; Pamplona, Fabricio Alano; Prediger, Rui Daniel Schroder

2008-01-01

296

Enhanced release of adenosine in rat hind paw following spinal nerve ligation: involvement of capsaicin-sensitive sensory afferents  

Microsoft Academic Search

Modulation of endogenous adenosine levels by inhibition of adenosine metabolism produces a peripheral antinociceptive effect in a neuropathic pain model. The present study used microdialysis to investigate the neuronal mechanisms modulating extracellular adenosine levels in the rat hind paw following tight ligation of the L5 and L6 spinal nerves. Subcutaneous injection of 50 ?l saline into the nerve-injured paw induced

X. J Liu; T. D White; J Sawynok

2002-01-01

297

Communications: Near edge x-ray absorption fine structure spectroscopy of aqueous adenosine triphosphate at the carbon and nitrogen  

E-print Network

Communications: Near edge x-ray absorption fine structure spectroscopy of aqueous adenosine and carbon K-edges was used to study the hydration of adenosine triphosphate in liquid microjets. The total of adenosine triphosphate ATP to the corresponding diphosphate is able to thermodynamically drive many

Cohen, Ronald C.

298

Limits of Ligand Selectivity from Docking to Models: In Silico Screening for A1 Adenosine Receptor Antagonists  

E-print Network

Limits of Ligand Selectivity from Docking to Models: In Silico Screening for A1 Adenosine Receptor models for the A1 adenosine receptor (A1AR) and docked ,2.2 M lead-like compounds. High-ranking molecules of Ligand Selectivity from Docking to Models: In Silico Screening for A1 Adenosine Receptor Antagonists. PLo

Sali, Andrej

299

N-H Stretching Excitations in Adenosine-Thymidine Base Pairs in Solution: Pair Geometries, Infrared Line Shapes, and Ultrafast  

E-print Network

N-H Stretching Excitations in Adenosine-Thymidine Base Pairs in Solution: Pair Geometries, Infrared vibrations of adenosine-thymidine base pairs in chloroform solution with linear and nonlinear infrared spectroscopy. Based on estimates from NMR measurements and ab initio calculations, we conclude that adenosine

Mukamel, Shaul

300

An adenosine-to-inosine tRNA-editing enzyme that can perform C-to-U deamination of DNA  

E-print Network

An adenosine-to-inosine tRNA-editing enzyme that can perform C-to-U deamination of DNA Mary Anne T (received for review February 24, 2007) Adenosine-to-inosine editing in the anticodon of tRNAs is essential for viability. Enzymes mediating tRNA adenosine deamination in bacteria and yeast contain cytidine deaminase

Papavasiliou, F. Nina

301

N-H Stretching Modes of Adenosine Monomer in Solution Studied by Ultrafast Nonlinear Infrared Spectroscopy and Ab Initio  

E-print Network

N-H Stretching Modes of Adenosine Monomer in Solution Studied by Ultrafast Nonlinear Infrared modified adenosine monomer dissolved in chloroform. For the single-quantum excitation manifold, the normal. In this article, the N-H stretching modes of adenosine monomer in chloroform solution (Figure 1) are studied

Mukamel, Shaul

302

Biophysical Journal Volume 70 May 1997 2275-2284 Adenosine Conformations of Nucleotides Bound to Methionyl tRNA  

E-print Network

Biophysical Journal Volume 70 May 1997 2275-2284 Adenosine Conformations of Nucleotides Bound with the observed curves. The final structures deduced for the adenosine moieties in the three complexes are very common motif for the recognition and binding of the adenosine moiety at the active sites of ATP

Paris-Sud XI, Université de

303

J Physiol 589.2 (2011) pp 283295 283 The dynamics of single spike-evoked adenosine release  

E-print Network

J Physiol 589.2 (2011) pp 283­295 283 The dynamics of single spike-evoked adenosine release-technicalsummaryAdenosinemodulatesbrainactivityinbothhealthanddisease.Although we know a lot about adenosine action, we know little about how it is released and its cellular sources. We have previously shown that adenosine can be released in the cerebellum by a train of action

Richardson, Magnus

304

Comparison of Adenosine and Exercise Stress Test for Quantitative Perfusion Imaging in Patients on Beta-Blocker Therapy  

Microsoft Academic Search

Beta-blocker therapy is used to decrease myocardial ischemia during exercise but may cause suboptimal diagnostic performance in exercise stress testing. The aim of the present study was to compare results of quantitative technetium-99-sestamibi single photon emission tomography (SPECT), following exercise stress test or pharmacological stress test with adenosine. We chose adenosine as comparison, since betablockers may not interfere with adenosine

Roland Müller-Suur; Sven V. Eriksson; Lars Erik Strandberg; Laszlo Mesko

2001-01-01

305

Release of adenosine and ATP in the brain of the freshwater turtle ( Trachemys scripta) during long-term anoxia  

Microsoft Academic Search

Extracellular adenosine and ATP levels were monitored by microdialysis in the striatum of the freshwater turtle Trachemys scripta during long-term N2 respiration. After an initial rise in extracellular adenosine, a second peak of longer duration and higher in intensity, followed. The frequencies of these adenosine cycles varied considerably between individual turtles, such that the shortest time between the peaks was

Peter L Lutz; Sandra Kabler

1997-01-01

306

Autophagy occurs within an hour of adenosine triphosphate treatment after nerve cell damage: the neuroprotective effects of adenosine triphosphate against apoptosis  

PubMed Central

After hypoxia, ischemia, or inflammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, flow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations (2, 4, 6, 8, 10 mmol/L) over time (1, 2, 3, and 6 hours) on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SY5Y cells. The enhanced autophagy first appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury. PMID:25368646

Lu, Na; Wang, Baoying; Deng, Xiaohui; Zhao, Honggang; Wang, Yong; Li, Dongliang

2014-01-01

307

Activity regulation of adenosine deaminases acting on RNA (ADARs).  

PubMed

Adenosine deaminases acting on RNA (ADARs) are the enzymes that are responsible for the A to I RNA editing process in mammals, which is an important mechanism that increases molecular diversity. A to I RNA editing consists of an enzymatic conversion of specific adenosine in pre-mRNA, leading to alteration of the properties of both the RNA itself and the translated protein. Currently, the importance of this phenomenon is increasingly recognized as it affects a diverse set of cellular pathways. ADAR function within the cell, especially in the neurons, is to diversify the features of a limited set of unique transcripts, mostly neurotransmitter receptors; however, a growing set of target is going to be discovered, increasing the importance of the RNA editing event in the proper physiology of the cell. Despite the functional relevance of these enzymes, there is a gap of knowledge in the mechanisms that regulate ADAR activity and consequently about the modulation of RNA editing process. This review summarizes ongoing investigations of ADAR regulation at the transcriptional, post-transcriptional and post-translational level and addresses new hypothetical mechanisms that are capable of modulating ADAR activity, including subcellular localization, dimerization and interaction with trans-acting factors. PMID:22113393

Orlandi, Cesare; Barbon, Alessandro; Barlati, Sergio

2012-02-01

308

Sawhorse waveform voltammetry for selective detection of adenosine, ATP, and hydrogen peroxide.  

PubMed

Fast-scan cyclic voltammetry (FSCV) is an electrochemistry technique which allows subsecond detection of neurotransmitters in vivo. Adenosine detection using FSCV has become increasingly popular but can be difficult because of interfering agents which oxidize at or near the same potential as adenosine. Triangle shaped waveforms are traditionally used for FSCV, but modified waveforms have been introduced to maximize analyte sensitivity and provide stability at high scan rates. Here, a modified sawhorse waveform was used to maximize the time for adenosine oxidation and to manipulate the shapes of cyclic voltammograms (CVs) of analytes which oxidize at the switching potential. The optimized waveform consists of scanning at 400 V/s from -0.4 to 1.35 V and holding briefly for 1.0 ms followed by a ramp back down to -0.4 V. This waveform allows the use of a lower switching potential for adenosine detection. Hydrogen peroxide and ATP also oxidize at the switching potential and can interfere with adenosine measurements in vivo; however, their CVs were altered with the sawhorse waveform and they could be distinguished from adenosine. Principal component analysis (PCA) was used to determine that the sawhorse waveform was better than the triangle waveform at discriminating between adenosine, hydrogen peroxide, and ATP. In slices, mechanically evoked adenosine was identified with PCA and changes in the ratio of ATP to adenosine were observed after manipulation of ATP metabolism by POM-1. The sawhorse waveform is useful for adenosine, hydrogen peroxide, and ATP discrimination and will facilitate more confident measurements of these analytes in vivo. PMID:25005825

Ross, Ashley E; Venton, B Jill

2014-08-01

309

Expression and pharmacological characterization of a stimulatory subtype of adenosine receptor in fetal chick ventricular myocytes.  

PubMed

Ventricular and atrial myocytes cultured from chick embryos 14 days in ovo were used as model systems to study cardiac adenosine receptors. In membranes of ventricular cultures, blocking of the A1-adenosine receptor pathway by the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or by pertussis toxin treatment of the myocyte resulted in a significant adenosine agonist-mediated stimulation of the adenylate cyclase activity. The maximal increases in adenylate cyclase activity caused by the equipotent or the A2-adenosine receptor-selective agonists (from 52.1 +/- 3% to 63 +/- 10% [mean +/- SEM]) were significantly greater than those caused by the A1-selective agonists (from 11 +/- 5% to 34.6 +/- 7%) (p less than 0.01, by t test, n = 4-8). However, in membranes of atrial myocytes, when A1-subtype had been blocked, the various adenosine agonists had no effect on the adenylate cyclase activity. Whether the stimulatory adenylate cyclase-coupled adenosine receptor is also capable of stimulating contractility in the intact ventricular myocyte was next investigated. In ventricular but not in atrial cells, the various adenosine agonists caused an increase in the contractile amplitude in the presence of DPCPX or in myocytes preexposed to pertussis toxin. The increase in contraction amplitude caused by each agonist was expressed as percent of maximum (maximum is the increase in contractility caused by 2.4 mM calcium). In the pertussis toxin-treated myocyte, the maximal increases caused by the equipotent or A2-agonists (NECA, MECA, CV-1808, and CGS21680, from 49.6 +/- 3% to 52.5 +/- 6%, n = 8-12) were significantly greater than those elicited by the A1-agonists (2-CADO, S-PIA, R-PIA, and DCCA, from 12 +/- 4% to 37 +/- 3%, n = 8) (p less than 0.05, by t test). These data demonstrated that a stimulatory adenosine receptor, likely the A2-adenosine receptor, was present on the ventricular but not the atrial myocytes and was linked directly to a stimulation of the cardiac contractility. The functional effects mediated by the A1-subtype became manifested in the presence of isoproterenol, as evidence by an inhibition of the isoproterenol-stimulated increases in adenylate cyclase activity and in cardiac contractility by adenosine agonists. Thus, both subtypes of adenosine receptors, each mediating opposing responses, were present on the ventricular myocytes, whereas only the A1-subtype was found in the atria. The presence of a stimulatory functional A2-adenosine receptor may help explain the absence of a direct negative inotropic response to adenosine in the ventricle. PMID:1727688

Xu, D; Kong, H Y; Liang, B T

1992-01-01

310

The bis(adenosin-N6-yl)alkanes, a family of potential dinucleoside-polyphosphate analogue precursors. Cytotoxicity, adenosine-receptor binding and metabolism.  

PubMed

A series of bis(adenosin-N6-yl)alkanes, in which two adenosine residues are linked via their N6 positions by alkyl bridges comprising between 2 and 14 methylene units, were synthesized as potential precursors to dinucleoside-polyphosphate analogues. These compounds were moderately cytotoxic to mammalian cells, the toxicity increasing with the length of the alkyl chain. For example, the dose of bis(adenosin-N6-yl)dodecane, A[CH2]12A, leading to 50% inhibition of cell growth (ID50) for BHK fibroblasts, Walker 256 carcinoma cells and S-49 T-lymphoma cells were 90 +/- 8, 100 +/- 5 and 23 +/- 4 microM respectively. A significant amount of A[CH2]12A bound to serum albumin in the growth media; thus the ID50 for S-49 cells grown in serum-free medium was 9 +/- 2 microM. The corresponding bis-cytidine analogues were much less toxic; however the presence of a second adenosine moeity/molecule had little significant effect on cell growth when compared to N6-alkyladenosines. Toxicity to S-49 cells was unaffected by the nucleoside-transporter inhibitor nitrobenzylthioinosine and was even higher (ID50 = 5 +/- 0.5 microM) towards nucleoside-transport-deficient AE-1 cells, showing that the analogues could pass freely through the plasma membrane. Interaction with A1 adenosine receptors was shown by displacement of [3H]N6-R-phenylisopropyladenosine (Kd = 6 nM) from rat adipocyte membranes, with Ki values of 45, 65, 85 and 390 nM for the compounds containing 12, 8, 6 and 4 methylene units, respectively. Affinity for human platelet membrane A2 adenosine receptors was about 100-fold less, however the compounds were weak A2 agonists, producing up to a threefold increase in intracellular cyclic AMP in WI-38/VA-13 cells. Thus, these compounds behave, not surprisingly, as adenosine analogues. In addition, A[CH2]12A was metabolized in vitro and intracellularly by adenosine kinase (Ki = 70 nM) and adenylate kinase to yield a number of phosphorylated derivatives with the potential to act as diadenosine polyphosphate analogues. One of these, the bismonophosphate, was recognized by and inhibited adenylate kinase more effectively than adenosine(5')tetraphospho(5')adenosine (Ap4A, Ki = 3 microM). PMID:8391440

Chen, H; McLennan, A G

1993-06-15

311

BAY60-6583 acts as a partial agonist at adenosine A2B receptors.  

PubMed

BAY60-6583 [2-({6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-yl}sulfanyl)acetamide] is the most potent and selective adenosine A2B receptor (A2B AR) agonist known to date. Therefore, it has been widely used for in vitro and in vivo experiments. In the present study, we investigated the binding and functional properties of BAY60-6583 in various native and recombinant cell lines with different A2B AR expression levels. In cAMP accumulation and calcium mobilization assays, BAY60-6583 was found to be significantly less efficacious than adenosine or the adenosine derivative NECA. When it was tested in human embryonic kidney (HEK)293 cells, its efficacy correlated with the A2B expression level of the cells. In Jurkat T cells, BAY60-6583 antagonized the agonistic effect of NECA and adenosine as determined in cAMP accumulation assays. On the basis of these results, we conclude that BAY60-6583 acts as a partial agonist at adenosine A2B receptors. At high levels of the physiologic agonist adenosine, BAY60-6583 may act as an antagonist and block the effects of adenosine at A2B receptors. This has to be considered when applying the A2B-selective "agonist" BAY60-6583 in pharmacological studies, and previous research results may have to be reinterpreted. PMID:24633424

Hinz, Sonja; Lacher, Svenja K; Seibt, Benjamin F; Müller, Christa E

2014-06-01

312

Evidence for evoked release of adenosine and glutamate from cultured cerebellar granule cells  

SciTech Connect

Evoked release of ({sup 3}H)-D-aspartate which labels the neurotransmitter glutamate pool in cultured cerebellar granule cells was compared with evoked release of adenosine from similar cultures. It was found that both adenosine and (3H)-D-aspartate could be released from the neurons in a calcium dependent manner after depolarization of the cells with either 10-100 microM glutamate or 50 mM KCl. Cultures of cerebellar granule cells treated with 50 microM kainate to eliminate GABAergic neurons behaved in the same way. This together with the observation that cultured astrocytes did not exhibit a calcium dependent, potassium stimulated adenosine release strongly suggest that cerebellar granule cells release adenosine in a neurotransmitter-like fashion together with glutamate which is the classical neurotransmitter of these neurons. Studies of the metabolism of adenosine showed that in the granule cells adenosine is rapidly metabolized to ATP, ADP, and AMP, but in spite of this, adenosine was found to be released preferential to ATP.

Schousboe, A.; Frandsen, A.; Drejer, J. (Univ. of Copenhagen (Denmark))

1989-09-01

313

A new method of sampling blood for measurement of plasma adenosine  

SciTech Connect

The half-life of adenosine in human blood is 1-2 s at 37{degrees}C. To measure plasma adenosine concentration accurately, it is necessary to inhibit adenosine metabolism during transit of blood through the sampling catheter. We have tested a double-lumen catheter and a solution of compounds that inhibit adenosine metabolism (stop solution) for this purpose. Stop solution and radiolabeled adenosine were delivered via an inner lumen, mixed with blood at the catheter tip, and withdrawn to a collection syringe in an outer lumen. Extracellular recovery of label was 89 +/- 5% and proportional to the quantity of label added to blood. In contrast, when blood and radiolabel were mixed with stop solution in the collecting syringe only after passage through the catheter, recovery of radiolabel was 7 +/- 3%. The importance of inhibiting pathways of adenosine formation and degradation or uptake during transit of blood through the catheter was demonstrated. The results suggest that a double-lumen catheter and stop solution are both necessary and suitable for collection of human blood to determine the concentration of plasma adenosine.

Shryock, J.C.; Boykin, M.T.; Hill, J.A.; Belardinelli, L. (Univ. of Florida, Gainesville (USA))

1990-04-01

314

Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, 57Fe Mössbauer, DFT, and in vitro cytotoxicity studies  

Microsoft Academic Search

Iron complexes (1–7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(Ln)Cl3]·H2O {where L1=N6-(2-fluorobenzyl)adenosine (1), L2=N6-(4-fluorobenzyl)adenosine (2), L3=N6-(2-trifluoromethylbenzyl)adenosine (3), L4=N6-(3-trifluoromethylbenzyl)adenosine (4), L5=N6-(4-trifluoromethylbenzyl)adenosine (5), L6=N6-(4-trifluoromethoxybenzyl)adenosine (6), and L7=N6-(4-chlorobenzyl)adenosine (7)} have been synthesized. The compounds have been characterized by elemental analysis, variable-temperature and in-field 57Fe Mössbauer, ES+ MS, FTIR, 1H and 13C NMR spectroscopies, magnetochemical and conductivity measurements, thermal (TGA\\/DSC\\/DTA) analyses, and DFT

Zden?k Trávní?ek; Ji?í Mikulík; Michal ?ajan; Radek Zbo?il; Igor Popa

2008-01-01

315

Lack of Endogenous Adenosine Tonus on Sympathetic Neurotransmission in Spontaneously Hypertensive Rat Mesenteric Artery  

PubMed Central

Background Increased sympathetic activity has been implicated in hypertension. Adenosine has been shown to play a role in blood flow regulation. In the present study, the endogenous adenosine neuromodulatory role, in mesenteric arteries from normotensive and spontaneously hypertensive rats, was investigated. Methods and Results The role of endogenous adenosine in sympathetic neurotransmission was studied using electrically-evoked [3H]-noradrenaline release experiments. Purine content was determined by HPLC with fluorescence detection. Localization of adenosine A1 or A2A receptors in adventitia of mesenteric arteries was investigated by Laser Scanning Confocal Microscopy. Results indicate a higher electrically-evoked noradrenaline release from hypertensive mesenteric arteries. The tonic inhibitory modulation of noradrenaline release is mediated by adenosine A1 receptors and is lacking in arteries from hypertensive animals, despite their purine levels being higher comparatively to those determined in normotensive ones. Tonic facilitatory adenosine A2A receptor-mediated effects were absent in arteries from both strains. Immunohistochemistry revealed an adenosine A1 receptors redistribution from sympathetic fibers to Schwann cells, in adventitia of hypertensive mesenteric arteries which can explain, at least in part, the absence of effects observed for these receptors. Conclusion Data highlight the role of purines in hypertension revealing that an increase in sympathetic activity in hypertensive arteries is occurring due to a higher noradrenaline/ATP release from sympathetic nerves and the loss of endogenous adenosine inhibitory tonus. The observed nerve-to-glial redistribution of inhibitory adenosine A1 receptors in hypertensive arteries may explain the latter effect. PMID:25158061

Sousa, Joana Beatriz; Vieira-Rocha, Maria Sofia; Sa, Carlos; Ferreirinha, Fatima; Correia-de-Sa, Paulo; Fresco, Paula; Diniz, Carmen

2014-01-01

316

Footprint traversal by adenosine-triphosphate-dependent chromatin remodeler motor  

NASA Astrophysics Data System (ADS)

Adenosine-triphosphate (ATP)-dependent chromatin remodeling enzymes (CREs) are biomolecular motors in eukaryotic cells. These are driven by a chemical fuel, namely, ATP. CREs actively participate in many cellular processes that require accessibility of specific segments of DNA which are packaged as chromatin. The basic unit of chromatin is a nucleosome where 146 bp ˜ 50 nm of a double-stranded DNA (dsDNA) is wrapped around a spool formed by histone proteins. The helical path of histone-DNA contact on a nucleosome is also called “footprint.” We investigate the mechanism of footprint traversal by a CRE that translocates along the dsDNA. Our two-state model of a CRE captures effectively two distinct chemical (or conformational) states in the mechanochemical cycle of each ATP-dependent CRE. We calculate the mean time of traversal. Our predictions on the ATP dependence of the mean traversal time can be tested by carrying out in vitro experiments on mononucleosomes.

Garai, Ashok; Mani, Jesrael; Chowdhury, Debashish

2012-04-01

317

Adenosine A2A Receptor Antagonists and Parkinson's Disease  

PubMed Central

This Review summarizes and updates the work on adenosine A2A receptor antagonists for Parkinson’s disease from 2006 to the present. There have been numerous publications, patent applications, and press releases within this time frame that highlight new medicinal chemistry approaches to this attractive and promising target to treat Parkinson’s disease. The Review is broken down by scaffold type and will discuss the efforts to optimize particular scaffolds for activity, pharmacokinetics, and other drug discovery parameters. The majority of approaches focus on preparing selective A2A antagonists, but a few approaches to dual A2A/A1 antagonists will also be highlighted. The in vivo profiles of compounds will be highlighted and discussed to compare activities across different chemical series. A clinical report and update will be given on compounds that have entered clinical trials. PMID:22860156

2011-01-01

318

Probing GPCR Structure: Adenosine and P2Y Nucleotide Receptors  

PubMed Central

The adenosine receptors (ARs) provide an example of how to accurately predict ligand recognition, even prior to the availability of a crystallographic structure. Homology modeling has been used to gain structural insight, in conjunction with site-directed mutagenesis and structure activity relationships of small molecular ligands. Recent X-ray structures greatly improved the accuracy of knowledge of AR ligand recogntion and furthermore characterized conformational changes induced by receptor activation. Now homology modeling extends these structural insights to related GPCRs and suggests new ligand structures. This strategy is also being applied to the eight subtypes of P2Y receptors for extracellular nucleotides, which lack X-ray structures and are best modeled by homology to the CXCR4 (peptide) receptor. Neoceoptors, as studied for three of the four AR subtypes, create a molecular complementarity between a mutant receptor and a chemically tailored agonist ligand to selectively enhance affinity, implying direct physical contact and thus validating docking hypotheses. PMID:23332701

Jacobson, Kenneth A.; Costanzi, Stefano; Deflorian, Francesca

2013-01-01

319

[Design, synthesis and biological activity evaluation of adenosine analogues].  

PubMed

N6-(2-Hydroxyethyl) adenosine, HEA (1), an active ingredient isolated from cultured mycelia of cordyceps species which is a famous traditional tonic in China, showed brain protective, sedative hypnotic activity in pharmacological tests. In order to explore novel non-benzodiazepine sedative-hypnotic agents, HEA was treated as the lead compound. Twenty three target compounds were designed and synthesized. Their chemical structures were characterized by 1H NMR, MS and elemental analysis. Pharmacological test in vivo showed that target compounds 8, 4, 13 were more active than HEA on locomotor and gasping activities of mice. Structure-activity relationships showed that the ribose moiety at N-9 position of adenine base was critical for activity. PMID:23984522

Wang, Dong-Mei; Liu, Xiao-Hui; Guo, Hui; Huang, Jun-Hua; Wang, Lin

2013-06-01

320

Adenosine deaminase gene amplification in deoxycoformycin-resistant mammalian cells.  

PubMed

Deoxycoformycin (dCF)-resistant mutants of rat hepatoma, mouse LMTK-, and Chinese hamster ovary (CHO) cells have been isolated and shown to overproduce adenosine deaminase (ADA). The overproduction of ADA was found to be due to ADA-gene amplification in rat and mouse cells but not in CHO cells. Deoxycoformycin-resistant rat hepatoma cells have large HSRs (homogeneously staining regions), mouse cells carry DMs (Double minutes), and CHO cells do not appear to have any gross chromosomal anomalies. When dCF-resistant rat hepatoma and mouse cells are selected by increasing the concentration of the inhibitor in small increments, there is a good correlation between the increase in ADA gene copy number and the increase in the level of expression of ADA, suggesting that all of the amplified genes are equally active in the expression of ADA. PMID:3873908

Rowland, P; Pfeilsticker, J; Hoffee, P A

1985-06-01

321

Extraction and analysis of adenosine triphosphate from aquatic environments  

USGS Publications Warehouse

A variety of adenosine triphosphate (ATP) extraction procedures have been investigated for their applicability to samples from aquatic environments. The cold sulfuric-oxalic acid procedure was best suited to samples consisting of water, periphyton, and sediments. Due to cation and fulvic acid interferences, a spike with a known quantity of ATP was necessary to estimate losses when sediments were extracted. Variable colonization densities for periphyton required that several replicates be extracted to characterize accurately the periphyton community. Extracted samples were stable at room temperature for one to five hours, depending on the ATP concentration, if the pH was below 2. Neutralized samples which were quick frozen and stored at -30C were stable for months. (USGS)

Stephens, Doyle W.; Shultz, David J.

1981-01-01

322

In vitro of adenosine on lymphocytes and erythrocytes from horses with combined immunodeficiency.  

PubMed Central

The effect of adenosine on the mitogenic response of peripheral blood lymphocytes (PBL) and on the nucleotide pools of erythrocytes from normal horses, horses heterozygous for the combined immunodeficiency (CID) trait (carriers), and foals with CID was studied. When PBL from normal, carrier, and CID horses were stimulated by phytohemagglutinin (PHA), concanavalin A, or pokeweed mitogen, [3H]thymidine uptake was inhibited by adenosine (0.1 microM) to 1.0 mM) in a dose-dependent manner. Adenosine (100 microM) mediated inhibition of [3H]thymidine uptake was prevented in both normal and carrier horse PBL by incubation with uridine. Uridine had no sparing effect on PBL from horses with CID. Differences were detected between human and horse PBL in response to adenosine and erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), a competitive inhibitor of adenosine deaminase. In the first assay, mitogen-stimulated PBL from horses were more sensitive to adenosine. In the second assay, adenosine was added to PBL cultures at various times after PHA addition. Adenosine inhibited mitogenesis in horse PBL if added within the first 24 h. In human PBL cultures, adenosine inhibited mitogenesis only if added within the first 4 h. The third assay measured capacity of PHA-stimulated human and horse lymphocytes to escape inhibition by adenosine or EHNA. At the end of a 72-h culture period, horse PBL were still inhibited of mitogenesis in both human and horse PBL. With prolonged incubation (72 h), synergistic inhibition was detected only in horse PB. With high-pressure liquid chromatography, nucleotide levels in erythrocytes of normal, carrier, and CID horses were found to be similar. Incubation with adenosine produced a 1.5- to 2-fold increase in total adenine nucleotide pools in erythrocytes from all horses. However, these increases were accompanied by alterations in the relative amounts of the nucleotide components. This was seen as a significant decrease in the ATP:(AMP plus ADP plus ATP) ratio and energy charge in erythrocytes from normal horses. In contrast, the ATP:(AMP plus ADP plus ATP) ratio decreased only slightly in erythrocytes from CID horses, whereas no change in the energy charge was detected. The data from these studies indicate a difference in adenosine metabolism exists between human and horse lymphoyctes, and an abnormality may exist in purine metabolism or in an interconnecting pathway in horses with CID. PMID:447864

Magnuson, N S; Perryman, L E

1979-01-01

323

Identification of the A2 Adenosine Receptor Binding Subunit by Photoaffinity Crosslinking  

Microsoft Academic Search

A high-affinity iodinated agonist radioligand for the A2 adenosine receptor has been synthesized to facilitate studies of the A2 adenosine receptor binding subunit. The radioligand 125I-labeled PAPA-APEC (125I-labeled 2-[4-2-{2-[(4-aminophenyl)methylcarbonylamino]ethylaminocarbonyl}- ethyl)phenyl]ethylamino-5'-N-ethylacarboxamidoadenosine) was synthesized and found to bind to the A2 adenosine receptor in bovine striatal membranes with high affinity (Kd = 1.5 nM) and A2 receptor selectivity. Competitive binding studies reveal

William W. Barrington; Kenneth A. Jacobson; Alan J. Hutchison; Michael Williams; Gary L. Stiles

1989-01-01

324

Structural and Metabolic Specificity of Methylthiocoformycin for Malarial Adenosine Deaminases  

SciTech Connect

Plasmodium falciparum is a purine auxotroph requiring hypoxanthine as a key metabolic precursor. Erythrocyte adenine nucleotides are the source of the purine precursors, making adenosine deaminase (ADA) a key enzyme in the pathway of hypoxanthine formation. Methylthioadenosine (MTA) is a substrate for most malarial ADAs, but not for human ADA. The catalytic site specificity of malarial ADAs permits methylthiocoformycin (MT-coformycin) to act as a Plasmodium-specific transition state analogue with low affinity for human ADA. The structural basis for MTA and MT-coformycin specificity in malarial ADAs is the subject of speculation. Here, the crystal structure of ADA from Plasmodium vivax (PvADA) in a complex with MT-coformycin reveals an unprecedented binding geometry for 5?-methylthioribosyl groups in the malarial ADAs. Compared to malarial ADA complexes with adenosine or deoxycoformycin, 5?-methylthioribosyl groups are rotated 130 degrees. A hydrogen bonding network between Asp172 and the 3?-hydroxyl of MT-coformycin is essential for recognition of the 5?-methylthioribosyl group. Water occupies the 5?-hydroxyl binding site when MT-coformycin is bound. Mutagenesis of Asp172 destroys the substrate specificity for MTA and MT-coformycin. Kinetic, mutagenic, and structural analyses of PvADA and kinetic analysis of five other Plasmodium ADAs establish the unique structural basis for its specificity for MTA and MT-coformycin. Plasmodium gallinaceum ADA does not use MTA as a substrate, is not inhibited by MT-coformycin, and is missing Asp172. Treatment of P. falciparum cultures with coformycin or MT-coformycin in the presence of MTA is effective in inhibiting parasite growth.

Ho, M.; Cassera, M; Madrid, D; Ting, L; Tyler, P; Kim, K; Almo, S; Schramm, V

2009-01-01

325

Adenosine Deaminases Acting on RNA, RNA Editing, and Interferon Action  

PubMed Central

Adenosine deaminases acting on RNA (ADARs) catalyze adenosine (A) to inosine (I) editing of RNA that possesses double-stranded (ds) structure. A-to-I RNA editing results in nucleotide substitution, because I is recognized as G instead of A both by ribosomes and by RNA polymerases. A-to-I substitution can also cause dsRNA destabilization, as I:U mismatch base pairs are less stable than A:U base pairs. Three mammalian ADAR genes are known, of which two encode active deaminases (ADAR1 and ADAR2). Alternative promoters together with alternative splicing give rise to two protein size forms of ADAR1: an interferon-inducible ADAR1-p150 deaminase that binds dsRNA and Z-DNA, and a constitutively expressed ADAR1-p110 deaminase. ADAR2, like ADAR1-p110, is constitutively expressed and binds dsRNA. A-to-I editing occurs with both viral and cellular RNAs, and affects a broad range of biological processes. These include virus growth and persistence, apoptosis and embryogenesis, neurotransmitter receptor and ion channel function, pancreatic cell function, and post-transcriptional gene regulation by microRNAs. Biochemical processes that provide a framework for understanding the physiologic changes following ADAR-catalyzed A-to-I (?=?G) editing events include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA-structure-dependent activities such as microRNA production or targeting or protein–RNA interactions. PMID:21182352

George, Cyril X.; Gan, Zhenji; Liu, Yong

2011-01-01

326

Substrate- and product-affinity resins for adenosine deaminase obtained by immobilisation of adenosine and inosine via 2',3'-cyclic acetal derivatives.  

PubMed

Immobilised inosine (6a) and adenosine (6c) and their 5'-phosphates have been synthesized. Reaction of the nucleosides with ethyl levulinate, followed by saponification or phosphorylation and then saponification, gave the 2',3'-O-[1-(2-carboxyethyl)ethylidene] derivatives 3 and 4 and the corresponding 5'-phosphates 2b and 2d. 6-Aminohexylagarose (5) was severally coupled to 2b, 2d, 3, and 4 through the carboxyl groups to give the polymers 6a-d. Adenosine deaminase converts 3 into 4, and 6c into 6a. The polymers can be used as affinity resins for adenosine deaminase, which is bound more strongly to 6c than to 6a. The operational capacity of 6a for adenosine deaminase is constant at 15--25 degrees, but decreases by approximately 16% from 25 degrees to 35 degrees. The resin 6a has been used to separate adenosine deaminase from mixtures containing other enzymes, for example, guanase or alcohol dehydrogenase. PMID:647708

Rosemeyer, H; Seela, F

1978-04-01

327

Association of adenosine receptor gene polymorphisms and in vivo adenosine A1 receptor binding in the human brain.  

PubMed

Adenosine A1 receptors (A1ARs) and the interacting adenosine A2A receptors are implicated in neurological and psychiatric disorders. Variants within the corresponding genes ADORA1 and ADORA2A were shown associated with pathophysiologic alterations, particularly increased anxiety. It is unknown so far, if these variants might modulate the A1AR distribution and availability in different brain regions. In this pilot study, the influence of ADORA1 and ADORA2A variants on in vivo A1AR binding was assessed with the A1AR-selective positron emission tomography (PET) radioligand [(18)F]CPFPX in brains of healthy humans. Twenty-eight normal control subjects underwent PET procedures to calculate the binding potential BPND of [(18)F]CPFPX in cerebral regions and to assess ADORA1 and ADORA2A single nucleotide polymorphism (SNP) effects on regional BPND data. Our results revealed SNPs of both genes associated with [(18)F]CPFPX binding to the A1AR. The strongest effects that withstood even Bonferroni correction of multiple SNP testing were found in non-smoking subjects (N=22) for ADORA2A SNPs rs2236624 and rs5751876 (corr. Pall<0.05). SNP alleles previously identified at risk for increased anxiety like the rs5751876 T-allele corresponded to consistently higher A1AR availability in all brain regions. Our data indicate for the first time that variation of A1AR availability was associated with ADORA SNPs. The finding of increased A1AR availability in regions of the fear network, particularly in ADORA2A risk allele carriers, strongly warrants evaluation and replication in further studies including individuals with increased anxiety. PMID:24943643

Hohoff, Christa; Garibotto, Valentina; Elmenhorst, David; Baffa, Anna; Kroll, Tina; Hoffmann, Alana; Schwarte, Kathrin; Zhang, Weiqi; Arolt, Volker; Deckert, Jürgen; Bauer, Andreas

2014-12-01

328

Pharmacological probes for A1 and A2 adenosine receptors in vivo in feline pulmonary vascular bed.  

PubMed

Under conditions of controlled pulmonary blood flow and constant left atrial pressure, adenosine produces dose-dependent, tone-dependent responses in the pulmonary vascular (PV) bed of intact-chest, spontaneously breathing cats. The potency profile for adenosine receptor agonists to produce vasoconstriction at low baseline PV tone is 5'-(N-ethylcarboxamido)adenosine > or = CGS-21680 > or = 2-chloroadenosine (2-CADO) > or = [R]-N6-(2-phenylisopropyl)adenosine (R-PIA) > or = N6-cyclopentyladenosine > adenosine > > CV-1808. After an increase in PV tone with the use of an intralobar infusion of the thromboxane mimic U-46619, the potency profile for adenosine receptor agonists to produce vasodilation at elevated PV tone is 2-CADO > or = CV-1808 > or = CGS-21680 > R-PIA > or = adenosine. The selective A1 adenosine receptor antagonists xanthine amine congener (XAC) and 8-cyclopentyl-1,3-dipropylxanthine (DP-CPX) significantly antagonize the vasoconstrictor responses of adenosine and R-PIA at low baseline PV tone while having less effect on the vasodilator responses of adenosine, 2-CADO, and R-PIA at elevated PV tone. DPCPX antagonizes the vasoconstrictor responses of CGS-21680 at low baseline PV tone. The nonselective A1 and A2 adenosine receptor antagonist BWA-1433U significantly antagonizes vasoconstrictor responses of R-PIA and vasodilator responses of adenosine, 2-CADO, and R-PIA. These data support that adenosine produces vasoconstriction at low baseline PV tone and vasodilation at elevated PV tone in the feline PV bed by acting on A1 and A2 adenosine receptors, respectively. Compared with the adenosine receptor agonists tested in this in vivo model, R-PIA and CV-1808 are the most selective adenosine receptor agonists for A1 and A2 adenosine receptors, respectively, in the feline PV bed. R-PIA, CV-1808, DPCPX, and XAC may be used in this in vivo model to define the roles of A1 and A2 adenosine receptors in acute lung injury and pathophysiological changes in the pulmonary vasculature associated with pulmonary hypertension and edema formation in the same animal model. PMID:8779837

Neely, C F; Matot, I

1996-02-01

329

No Effect of Nutritional Adenosine Receptor Antagonists on Exercise Performance in the Heat.  

National Technical Information Service (NTIS)

Nutritional adenosine receptor antagonists can enhance endurance exercise performance in temperate environments, but their efficacy during heat stress is not well understood. This double-blinded, placebo-controlled study compared the effects of an acute d...

B. B. Michniak-Kohn, B. R. Ely, J. C. Rood, R. W. Kenefick, S. N. Cheuvront

2008-01-01

330

Adenosine-based molecular beacons as light-up probes for sensing heparin in plasma.  

PubMed

This study presents an adenosine-based molecular beacon (MB) for the selective and sensitive detection of heparin based on the competitive binding between heparin and the MB stem to coralyne. PMID:23563586

Kuo, Chia-Yin; Tseng, Wei-Lung

2013-05-21

331

Adenosine Inhibition of Ca Uptake by Synaptosomes as Function of Time of Electrical Stimulation  

Microsoft Academic Search

The effect of adenosine on Ca uptake by rat brain synaptosomes electrically stimulated was studied as function of time of stimulation (10, 30, 120 s). Inhibition of Ca uptake was more evident for 120 s.

M. L. Gonçalves; F. Pinto; J. A. Ribeiro

1991-01-01

332

Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles  

PubMed Central

Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery. PMID:22619519

Galagudza, Michael; Korolev, Dmitry; Postnov, Viktor; Naumisheva, Elena; Grigorova, Yulia; Uskov, Ivan; Shlyakhto, Eugene

2012-01-01

333

Cardiac sodium, potassium-adenosine triphosphatase as a possible site of adriamycin-induced cardiotoxicity.  

PubMed

Adriamycin ws tested as a possible inhibitor of cardiac sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase). At concentrations of 10(-4) M and lower, Adriamycin had no effect upon either ouabain-sensitive (Na-K-ATPase) or ouabain-insensitive adenosine triphosphatase activity in homogenates and microsomal fractions of cardiac tissue from several different species. Adriamycin inhibited adenosine triphosphatase activity at a concentration of 10(-3) M, but this was due to the inhibition of ouabain-insensitive adenosine triphosphatase rather than to inhibition of Na-K-ATPase. Under no condition was an inhibition of Na-K-ATPase activity by Adriamycin observed. These conditions included preincubation of the enzyme with Adriamycin, chelation of Ca2+, addition of reduced nicotinamide adenine dinucleotide phosphate, and variation of buffer and pH. It was concluded that Na-K-ATPase is not a likely site of Adriamycin-induced cardiotoxicity. PMID:6256069

Solomonson, L P; Halabrin, P R

1981-02-01

334

Rat cerebral-cortex adenosine deaminase activity and its subcellular distribution  

PubMed Central

A radioisotopic assay for adenosine deaminase (EC 3.5.4.4) is described together with its application in investigating the activity of the enzyme in rat cerebral cortex. Activity of the adenosine deaminase was determined to be 115nmol/min per g of tissue, measured in isoosmotic sucrose dispersions of the neocortex, and to be 170nmol/min per g of tissue after treatment with Triton X-100. The enzyme was concluded to be largely cytoplasmic, with a Km of 54–57?m for adenosine. Action of the deaminase, and other aspects of the metabolism of adenosine in intact neocortical tissue, were quantitatively appraised on the basis of the newly determined characteristics. PMID:4462574

Pull, Ian; McIlwain, Henry

1974-01-01

335

Caffeine, Adenosine Receptors and Estrogen in Toxin Models of Parkinson's Disease.  

National Technical Information Service (NTIS)

Substantial progress has been made toward each of the 3 Specific Aims (SAs) of our research project, 'Caffeine, adenosine receptors andestrogen in toxin models of Parkinson's disease (PD)'. The overarching hypothesis of the project is that multiple enviro...

M. A. Schwarzschild

2005-01-01

336

Laboratory procedures manual for the firefly luciferase assay for adenosine triphosphate (ATP)  

NASA Technical Reports Server (NTRS)

A manual on the procedures and instruments developed for the adenosine triphosphate (ATP) luciferase assay is presented. Data cover, laboratory maintenance, maintenance of bacterial cultures, bacteria measurement, reagents, luciferase procedures, and determination of microbal susceptibility to antibiotics.

Chappelle, E. W.; Picciolo, G. L.; Curtis, C. A.; Knust, E. A.; Nibley, D. A.; Vance, R. B.

1975-01-01

337

Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors.  

PubMed

Limonene is a major aromatic compound in essential oils extracted from citrus rind. The application of limonene, especially in aromatherapy, has expanded significantly, but its potential effects on cellular metabolism have been elusive. We found that limonene directly binds to the adenosine A(2A) receptor, which may induce sedative effects. Results from an in vitro radioligand binding assay showed that limonene exhibits selective affinity to A(2A) receptors. In addition, limonene increased cytosolic cAMP concentration and induced activation of protein kinase A and phosphorylation of cAMP-response element-binding protein in Chinese hamster ovary cells transfected with the human adenosine A(2A) receptor gene. Limonene also increased cytosolic calcium concentration, which can be achieved by the activation of adenosine A(2A) receptors. These findings suggest that limonene can act as a ligand and an agonist for adenosine A(2A) receptors. PMID:21134357

Park, Hyo Min; Lee, Ji Hae; Yaoyao, Jia; Jun, Hee Jin; Lee, Sung Joon

2011-01-01

338

Potentiation of Uterine Effects of Prostaglandin F2 by Adenosine 5 -Triphosphate  

E-print Network

, DSc, Julia T. Zefirova, MD, Tatiana P. Zefirova, PhD, Lilia E. Ziganshina, DSc, Charles H. V. Hoyle, DSc, and Geoffrey Burnstock, DSc OBJECTIVE: To investigate the interaction of exogenous adenosine 5

Burnstock, Geoffrey

339

Increased adenosine concentration in bronchoalveolar lavage fluid of horses with lower airway inflammation  

PubMed Central

Several reports have suggested a role for adenosine in the pathogenesis of chronic airway conditions and this has led to new therapeutic strategies to limit airway inflammation. In this study, detectable levels of adenosine in bronchoalveolar lavage (BAL) samples from 11 horses with non-infectious lower-airway inflammation and 14 healthy controls are reported, with significantly higher values in horses with airway inflammation. Although these increased levels did not correlate with changes in neutrophil percentage in BAL, a positive association between adenosine levels and signs of lower airway inflammation (clinical score) was observed. These novel findings support the hypothesis that adenosine may contribute to bronchoconstriction and also act as a pro-inflammatory mediator in the bronchoalveolar milieu of horses with airway inflammation. Further investigation of this axis could lead to new approaches for the treatment of highly prevalent lower airway inflammatory conditions in the horse. PMID:22206730

Zhang, Li; Franchini, Marco; Eser, Meret Wehrli; Jackson, Edwin K.; Dip, Ramiro

2013-01-01

340

Role of CNPase in the Oligodendrocytic Extracellular 2?,3?-cAMP-Adenosine Pathway  

PubMed Central

Extracellular adenosine 3?,5?-cyclic monophosphate (3?,5?-cAMP) is an endogenous source of localized adenosine production in many organs. Recent studies suggest that extracellular 2?,3?-cAMP (positional isomer of 3?,5?-cAMP) is also a source of adenosine, particularly in the brain in vivo post-injury. Moreover, in vitro studies show that both microglia and astrocytes can convert extracellular 2?,3?-cAMP to adenosine. Here we examined the ability of primary mouse oligodendrocytes and neurons to metabolize extracellular 2?,3?-cAMP and their respective adenosine monophosphates (2?-AMP and 3?-AMP). Cells were also isolated from mice deficient in 2?,3?-cyclic nucleotide-3?-phosphodiesterase (CNPase). Oligodendrocytes metabolized 2?,3?-cAMP to 2?-AMP with 10-fold greater efficiency than did neurons (and also more than previously examined microglia and astrocytes); whereas, the production of 3?-AMP was minimal in both oligodendrocytes and neurons. The production of 2?-AMP from 2?,3?-cAMP was reduced by 65% in CNPase -/- versus CNPase +/+ oligodendrocytes. Oligodendrocytes also converted 2?-AMP to adenosine, and this was also attenuated in CNPase -/- oligodendrocytes. Inhibition of classic 3?,5?-cAMP-3?-phosphodiesterases with 3-isobutyl-1-methylxanthine did not block metabolism of 2?,3?-cAMP to 2?-AMP and inhibition of classic ecto-5?-nucleotidase (CD73) with ?,?-methylene-adenosine-5?-diphosphate did not attenuate the conversion of 2?-AMP to adenosine. These studies demonstrate that oligodendrocytes express the extracellular 2?,3?-cAMP-adenosine pathway (2?,3?-cAMP ? 2?-AMP ? adenosine). This pathway is more robustly expressed in oligodendrocytes than in all other CNS cell types because CNPase is the predominant enzyme that metabolizes 2?,3?-cAMP to 2-AMP in CNS cells. By reducing levels of 2?,3?-cAMP (a mitochondrial toxin) and increasing levels of adenosine (a neuroprotectant), oligodendrocytes may protect axons from injury. PMID:23922219

Verrier, Jonathan D.; Jackson, Travis C.; Gillespie, Delbert G.; Janesko-Feldman, Keri; Bansal, Rashmi; Goebbels, Sandra; Nave, Klaus-Armin; Kochanek, Patrick M.; Jackson, Edwin K.

2014-01-01

341

Thallium-201 scintigraphy after intravenous infusion of adenosine compared with exercise thallium testing in the diagnosis of coronary artery disease  

SciTech Connect

Adenosine is an endogenously produced compound that has significant effects as a coronary and systemic vasodilator. Previous studies suggest that intravenous infusion of adenosine, coupled with thallium-201 scintigraphy, may have specific value as a noninvasive means of evaluating coronary artery disease. The purpose of this study was to compare the diagnostic value of adenosine thallium testing with that of standard exercise thallium testing. One hundred subjects were studied with exercise thallium imaging and thallium imaging after adenosine infusion, including 47 with angiographically proved coronary artery disease and 53 control subjects. The overall sensitivity of the thallium procedures was 81% for the exercise study and 83% for the adenosine study (p = NS); the specificity was 74% for the exercise study and 75% for the adenosine study (p = NS). The diagnostic accuracy of the exercise study was 77% and that of the adenosine study was 79%. Ninety-four percent of subjects had an adverse effect due to the adenosine infusion; however, most of these effects were mild and well tolerated. All adverse effects abated within 30 to 45 s of the termination of the study, consistent with the very brief half-life of the agent. Thus, thallium-201 scintigraphy after intravenous infusion of adenosine has a diagnostic value similar to that of exercise thallium testing for evaluation of coronary artery disease. Adenosine thallium testing may be particularly useful in evaluating patients unable to perform treadmill exercise testing.

Coyne, E.P.; Belvedere, D.A.; Vande Streek, P.R.; Weiland, F.L.; Evans, R.B.; Spaccavento, L.J. (Department of Medicine, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas (USA))

1991-05-01

342

Effect of adenosine and AICAR on ATP content and regional contractile function in reperfused canine myocardium  

Microsoft Academic Search

Summary We investigated whether the postischemic acceleration of adenosine triphosphate (ATP) synthesis by means of precursor infusion is beneficial for the contractile function of reperfused myocardium. A coronary artery was occluded for 45 min in 21 dogs to produce a marked but reversible ischemia. During the following 3 hours of reperfusion either adenosine (n=6) or AICAR (5-amino-imidazole-4-carboxamide-riboside) (n=6) was infused

H. M. Hoffmeister; M. Mauser; W. Schaper

1985-01-01

343

Adenosine A 2A receptor deficient mice are partially resistant to limbic seizures  

Microsoft Academic Search

The neuromodulator adenosine, acting through activation of four defined metabotropic receptors called A1, A2A, A2B and A3, has been proposed as an endogenous anticonvulsant. Here, the consequences of deleting the adenosine A2A receptor have been examined in different experimental models of epilepsy. A2AR KO mice were not protected against seizures originating from brainstem structures, namely electroshock-induced seizures.\\u000a The intensities of

Malika El Yacoubi; Catherine Ledent; Marc Parmentier; Jean Costentin; Jean-Marie Vaugeois

2009-01-01

344

Receptor crosstalk: haloperidol treatment enhances A 2A adenosine receptor functioning in a transfected cell model  

Microsoft Academic Search

A2A adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders.\\u000a It is noteworthy that the responses evoked by A2A adenosine receptors are regulated by D2 dopamine receptor ligands. These two receptors are co-expressed at the level of the basal ganglia and interact to form functional\\u000a heterodimers. In this context, possible changes in A2A

Maria Letizia Trincavelli; Serena Cuboni; Mario Catena Dell’Osso; Roberto Maggio; Karl-Norbert Klotz; Francesca Novi; Anna Panighini; Simona Daniele; Claudia Martini

2010-01-01

345

Toxicity of Cordycepin in Combination with the Adenosine Deaminase Inhibitor 2?Deoxycoformycin in Beagle Dogs  

Microsoft Academic Search

For 3 consecutive days, the nucleoside cordycepin (3?-deoxyadenosine) was administered as 1-hr iv infusions (0, 1, 4, 8, 10, or 20 mg\\/kg\\/day) to dogs. These doses were given 1 hr after a bolus iv injection (0.25 mg\\/kg\\/day) of 2?-deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase. The hypothesis was that dCF would affect the toxicity of cordycepin. Plasma adenosine deaminase

Larry E. Rodman; Daniel R. Farnell; John M. Coyne; Paula W. Allan; Donald L. Hill; Kimberly L. K. Duncan; Joseph E. Tomaszewski; Adaline C. Smith; John G. Page

1997-01-01

346

Adenosine A1 receptor-mediated inhibition of surfactant secretion in rat type II pneumocytes.  

PubMed

Phosphatidylcholine secretion in type II pneumocytes has been reported to be stimulated by P1 and P2 purinoceptor agonists. P1 receptors are divided into A1 and A2 subtypes with opposite effects on the levels of adenosine 3',5'-cyclic monophosphate (cAMP). Stimulated secretion in type II cells is mediated by the A2 receptor and accompanied by an increase in cAMP concentration. We now report evidence suggesting the existence of an A1 receptor-inhibiting secretion in type II cells from adult rats. The rate of phosphatidylcholine secretion was approximately doubled by 5'(N-ethylcarboxyamido) adenosine (NECA), terbutaline, and forskolin, all of which increase cAMP levels. Adenosine deaminase increased the stimulatory effect of these agonists to approximately three-fold but it had not effect on secretion stimulated by agonists which do not increase cAMP levels. The effect of adenosine deaminase on terbutaline-stimulated secretion was antagonized by selective adenosine A1 receptor agonists, N6-cyclopentyladenosine (CPA) and 1-deaza-2-chloro-N6-cyclopentyladenosine (DCCA). The maximum inhibitory effects of CPA and DCCA were achieved at 10(-9) M and 10(-11) M, respectively. At these concentrations CPA and DCCA had no effect on the rate of basal secretion or on terbutaline-stimulated secretion in the absence of adenosine deaminase. We suggest that adenosine deaminase stimulates phosphatidylcholine secretion by removing adenosine that occupies A1 receptors, thus reversing inhibition of cAMP-mediated secretion. PMID:2305899

Gobran, L I; Rooney, S A

1990-02-01

347

Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies.  

PubMed

Neurodegenerative disorders are some of the most feared illnesses in modern society, with no effective treatments to slow or halt this neurodegeneration. Several decades after the earliest attempt to treat Parkinson's disease using caffeine, tremendous amounts of information regarding the potential beneficial effect of caffeine as well as adenosine drugs on major neurodegenerative disorders have accumulated. In the first part of this review, we provide general background on the adenosine receptor signaling systems by which caffeine and methylxanthine modulate brain activity and their role in relationship to the development and treatment of neurodegenerative disorders. The demonstration of close interaction between adenosine receptor and other G protein coupled receptors and accessory proteins might offer distinct pharmacological properties from adenosine receptor monomers. This is followed by an outline of the major mechanism underlying neuroprotection against neurodegeneration offered by caffeine and adenosine receptor agents. In the second part, we discuss the current understanding of caffeine/methylxantheine and its major target adenosine receptors in development of individual neurodegenerative disorders, including stroke, traumatic brain injury Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple sclerosis. The exciting findings to date include the specific in vivo functions of adenosine receptors revealed by genetic mouse models, the demonstration of a broad spectrum of neuroprotection by chronic treatment of caffeine and adenosine receptor ligands in animal models of neurodegenerative disorders, the encouraging development of several A(2A) receptor selective antagonists which are now in advanced clinical phase III trials for Parkinson's disease. Importantly, increasing body of the human and experimental studies reveals encouraging evidence that regular human consumption of caffeine in fact may have several beneficial effects on neurodegenerative disorders, from motor stimulation to cognitive enhancement to potential neuroprotection. Thus, with regard to neurodegenerative disorders, these potential benefits of methylxanthines, caffeine in particular, strongly argue against the common practice by clinicians to discourage regular human consumption of caffeine in aging populations. PMID:20859800

Chen, Jiang-Fan; Chern, Yijuang

2011-01-01

348

Cloning of cDNAs Encoding Mammalian Double-Stranded RNA-Specific Adenosine Deaminase  

Microsoft Academic Search

Double-stranded RNA (dsRNA)-specific adenosine deaminase converts adenosine to inosine in dsRNA. The protein has been purified from calf thymus, and here we describe the cloning of cDNAs encoding both the human and rat proteins as well as a partial bovine clone. The human and rat clones are very similar at the aminoacidlevelexceptattheirNterminiandcontainthreedsRNAbindingmotifs,aputativenucleartargeting signal, and a possible deaminase motif. Antibodies raised

MARY A. O'CONNELL; SABINE KRAUSE; MIYOKO HIGUCHI; J. JUSTIN HSUAN; NICHOLAS F. TOTTY; ANDREAS JENNY; ANDWALTER KELLER

1995-01-01

349

Effect of adenosine in extracellular matrix synthesis in human and rat mesangial cells  

Microsoft Academic Search

Adenosine (ADO) is an intermediary metabolite of adenosine trisphosphate degradation and a vasoactive mediator. We showed\\u000a previously that ADO induces contraction and proliferation in rat mesangial cells by a mechanism involving A1 and A2 receptors.\\u000a The studies concerning the effect of ADO on extracellular matrix (ECM) accumulation in mesangial cells are scarce. The purpose\\u000a of our study was to evaluate

Carlos Martínez-Salgado; Begoña García-Cenador; Isabel Fuentes-Calvo; Juan F. Macías Núñez; José M. López-Novoa

2007-01-01

350

Adenosine stimulates connexin 43 expression and gap junctional communication in pituitary folliculostellate cells.  

PubMed

Adenosine is known to stimulate interleukin (IL)-6 and vascular endothelial growth factor (VEGF) secretion from pituitary TtT/GF folliculostellate [corrected] (FS) cells indicating that it is an important paracrine regulator of anterior pituitary function. This study demonstrates that rodent anterior pituitary cell lines produce extracellular adenosine that is able to increase intercellular gap junction communication in FS cells. Ecto-5'-nucleotidase (CD73), the enzyme that generates adenosine from AMP, was demonstrated by immunocytochemistry in approximately 20% of anterior pituitary cells, and some of these cells colocalized with prolactin and growth hormone. CD73 mRNA and protein were detected in GH3 and MMQ (somatotroph-lactotroph lineages) and TtT/GF cells, and enzyme activity was demonstrated by the conversion of exogenously added fluorescent ethenoAMP to ethenoadenosine. Adenosine production, as measured by HPLC, was detected in GH3 (1 microM/h) and MMQ (3 microM/h) but not in TtT/GF cells. Adenosine (EC50: 0.5 microM) and NECA (universal adenosine receptor agonist; EC50 0.1 microM) stimulated connexin 43 (Cx43) mRNA and protein expression within 1-2 h in TtT/GF cells. Adenosine and NECA also stimulated gap junctional intercellular communication (as assessed by transmission of Alexa Fluor 488) by 6- to 8-fold in comparison with untreated TtT/GF cells. In cocultures of MMQ and TtT/GF cells, Cx43 expression in TtT/GF cells increased in proportion to the number of MMQ cells plated out. These data suggest that adenosine, formed locally in the anterior pituitary gland can stimulate gap junction communication in FS cells. PMID:17065216

Lewis, B Mary; Pexa, Annette; Francis, Karen; Verma, Vandana; McNicol, Anne M; Scanlon, Maurice; Deussen, Andreas; Evans, W Howard; Rees, D Aled; Ham, Jack

2006-12-01

351

Opiate-induced Changes in Brain Adenosine Levels and Narcotic Drug Responses  

PubMed Central

We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. Escalating morphine doses (10–40 mg/kg) administered over a 4-day period selectively induced a two-fold decrease (p<0.00005) in adenosine abundance in the brainstem of C57BL/6 mice, which exhibited symptoms of narcotic drug dependence; but did not decrease adenosine abundance in 129Sv1 mice, which do not exhibit symptoms of dependence. Based on this finding, the effect of adenosine on dependence was investigated in genetically engineered mice with alterations in adenosine tone in the brain and in pharmacologic experiments. Morphine withdrawal behaviors were significantly diminished (P<0.0004) in genetically engineered mice with reduced adenosine tone in the brainstem, and by treatment with an adenosine receptor1 (A1) agonist (2-chloro-N6-cyclopentyladenosine, 0.5 mg/kg) or an A2a receptor (A2a) antagonist (SCH 58261 1 mg/kg). These results indicate that adenosine homeostasis plays a crucial role in narcotic drug responses. Opiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal. PMID:23098802

Wu, Manhong; Sahbaie, Peyman; Zheng, Ming; Lobato, Robert; Boison, Detlev; Clark, J. David; Peltz, Gary

2012-01-01

352

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine  

Microsoft Academic Search

The carotid body (CB) is the main arterial chemoreceptor with a low threshold to hypoxia. CB activity is augmented by A2-adenosine receptors stimulation and attenuated by D2-dopamine receptors. The effect of aging on ventilatory responses mediated by the CB to hypoxia, ischemia, and to adenosine\\u000a and dopamine administration is almost unknown. This study aims to investigate the ventilatory response to

Teresa Castro Monteiro; Joana Rita Batuca; Ana Obeso; Constancio González; Emília Carreira Monteiro

353

Adenosine in Peripheral Chemoreception: New Insights into a Historically Overlooked Molecule – Invited Article  

Microsoft Academic Search

In the present article we review in a concise manner the literature on the general biology of adenosine signalling.\\u000a In the first section we describe briefly the historical aspects of adenosine research. In the second section is presented\\u000a the biochemical characteristics of this nucleoside, namely its metabolism and regulation, and its physiological actions. In\\u000a the third section we have succinctly

S. V. Conde; E. C. Monteiro; A. Obeso; C. Gonzalez

354

Enhanced Release of Adenosine Under Cell-Damaging Conditions in the Developing and Adult Mouse Hippocampus  

Microsoft Academic Search

The inhibitory neuromodulator adenosine has been thought to act as an endogenous neuroprotectant against cerebral ischemia and neuronal damage. The release of preloaded [3H]adenosine from hippocampal slices from developing (7-day-old) and adult (3-month-old) mice was characterized using a superfusion system under various cell-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress, and the presence of free radicals and metabolic poisons. The

Pirjo Saransaari; Simo S. Oja

2003-01-01

355

Adenosine stimulates anabolic metabolism in developing castor bean ( Ricinus communis L.) cotyledons  

Microsoft Academic Search

In previous experiments it was shown that Castor-bean (Ricinus communis) endosperm releases carbohydrates, amino acids and nucleoside derivatives, which are subsequently imported into the developing\\u000a cotyledons (Kombrink and Beevers in Plant Physiol 73:370–376, 1983). To investigate the importance of the most prominent nucleoside adenosine for the metabolism of growing Ricinus seedlings, we supplied adenosine to cotyledons of 5-days-old seedlings after

Martin Flörchinger; Marc Zimmermann; Michaela Traub; H. Ekkehard Neuhaus; Torsten Möhlmann

2006-01-01

356

Blockade of adenosine and dopamine receptors inhibits the development of rapid tolerance to ethanol in mice  

Microsoft Academic Search

Rationale  Several reports have suggested the involvement of brain adenosine and dopamine receptors in different actions produced by\\u000a ethanol such as motor incoordination or anxiolytic, hypnotic and reinforcing effects. The co-localization and interaction\\u000a between adenosine and dopamine receptors in different brain regions has also been well documented. However, few studies have\\u000a demonstrated the involvement of these mechanisms in the tolerance induced

Luciano C. Batista; Rui D. S. Prediger; Gina S. Morato; Reinaldo N. Takahashi

2005-01-01

357

Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport  

Microsoft Academic Search

Previously, we have shown that pancreatic acini release adenosine triphosphate (ATP) and ATP-handling enzymes, and pancreatic\\u000a ducts express various purinergic P2 receptors. The aim of the present study was to establish whether pancreatic ducts also\\u000a express adenosine receptors and whether these could be involved in secretory processes, which involve cystic fibrosis transmembrane\\u000a regulator (CFTR) Cl? channels or Ca2+-activated Cl? channels

Ivana Novak; Susanne E. Hede; Mette R. Hansen

2008-01-01

358

Functional assessment of coronary artery flow using adenosine stress dual-energy CT: a preliminary study  

Microsoft Academic Search

We attempted to assess coronary artery flow using adenosine-stress and dual-energy mode with dual-source CT (DE-CT). Data\\u000a of 18 patients with suspected coronary arteries disease who had undergone cardiac DE-CT were retrospectively analyzed. The\\u000a patients were divided into two groups: 10 patients who performed adenosine stress CT, and 8 patients who performed rest CT\\u000a as controls. We reconstructed an iodine

Michinobu Nagao; Teruhito Kido; Kouki Watanabe; Hideyuki Saeki; Hideki Okayama; Akira Kurata; Kohei Hosokawa; Hiroshi Higashino; Teruhito Mochizuki

2011-01-01

359

Diminished arterial smooth muscle response to adenosine during NaK pump inhibition  

Microsoft Academic Search

The possibility of a role of the sarcolemmal Na-K pump of arterial smooth muscle in the mechanism of action of adenosine was explored in this study. Isolated helical strips of rabbit coronary and femoral arteries were suspended in organ baths with physiological salt solution, and isometric contractions were recorded. Concentration-dependent relaxations produced by adenosine were attenuated during Na-K pump inhibition.

Duane H. Foley

1984-01-01

360

Intrinsic A(1) adenosine receptor activation during ischemia or reperfusion improves recovery in mouse hearts.  

PubMed

We assessed the role of A(1) adenosine receptor (A(1)AR) activation by endogenous adenosine in the modulation of ischemic contracture and postischemic recovery in Langendorff-perfused mouse hearts subjected to 20 min of total ischemia and 30 min of reperfusion. In control hearts, the rate-pressure product (RPP) and first derivative of pressure development over time (+dP/dt) recovered to 57 +/- 3 and 58 +/- 3% of preischemia, respectively. Diastolic pressure remained elevated at 20 +/- 2 mmHg (compared with 3 +/- 1 mmHg preischemia). Interstitial adenosine, assessed by microdialysis, rose from approximately 0.3 to 1.9 microM during ischemia compared with approximately 15 microM in rat heart. Nonetheless, these levels will near maximally activate A(1)ARs on the basis of effects of exogenous adenosine and 2-chloroadenosine. Neither A(1)AR blockade with 200 nM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) during the ischemic period alone nor A(1)AR activation with 50 nM N(6)-cyclopentyladenosine altered rapidity or extent of ischemic contracture. However, ischemic DPCPX treatment significantly depressed postischemic recovery of RPP and +dP/dt (44 +/- 3 and 40 +/- 4% of preischemia, respectively). DPCPX treatment during the reperfusion period alone also reduced recovery of RPP and +dP/dt (to 44 +/- 2 and 47 +/- 2% of preischemia, respectively). These data indicate that 1) interstitial adenosine is lower in mouse versus rat myocardium during ischemia, 2) A(1)AR activation by endogenous adenosine or exogenous agonists does not modify ischemic contracture in murine myocardium, 3) A(1)AR activation by endogenous adenosine during ischemia attenuates postischemic stunning, and 4) A(1)AR activation by endogenous adenosine during the reperfusion period also improves postischemic contractile recovery. PMID:11045950

Peart, J; Headrick, J P

2000-11-01

361

Stability of undiluted and diluted adenosine at three temperatures in syringes and bags.  

PubMed

The stability of adenosine in various diluents in polypropylene syringes and polyvinyl chloride (PVC) bags at three temperatures was studied. Portions of pooled undiluted adenosine infusion (3 mg/ mL) were stored in 60-mL capped syringes, 20 for each storage condition. Adenosine infusions were prepared by mixing adenosine with 5% dextrose injection, 0.9% sodium chloride injection, lactated Ringer's injection, or 5% dextrose and lactated Ringer's injection to produce a concentration of 0.75 mg/mL. Samples of each infusion were stored in 60-mL capped syringes and 50-mL bags, 20 syringes and 20 bags for each storage condition. Syringes and bags were stored in the dark at 25, 5, and -15 degrees C. At various sampling times, three syringes and three bags of each infusion were removed for visual inspection, pH measurement, and high-performance liquid chromatographic analysis. At 10 and 16 days, fungal growth at 25 degrees C was suspected in the infusions prepared with 5% dextrose injection. For all other samples, there was no evidence of precipitation or change in pH. The concentration of adenosine remained constant in all samples at all storage conditions. Adenosine 3 mg/mL was stable in polypropylene syringes for 7 days at 25 degrees C, 14 days at 5 degrees C, and 28 days at -15 degrees C; adenosine 0.75 mg/ mL in 0.9% sodium chloride injection and in 5% dextrose injection was stable in polypropylene syringes and PVC bags for 16 days at 25, 5, and -15 degrees C; and adenosine 0.75 mg/mL in lactated Ringer's injection and in 5% dextrose and lactated Ringer's injection was stable in syringes and bags for 14 days at 25, 5, and -15 degrees C. PMID:9522931

Ketkar, V A; Kolling, W M; Nardviriyakul, N; VanDer Kamp, K; Wurster, D E

1998-03-01

362

Roles of the Adenosine Receptor and CD73 in the Regulatory Effect of ?? T Cells  

PubMed Central

The adenosine A2A receptor (A2AR), the main functional adenosine receptor on murine T cells, plays a unique role in the attenuation of inflammation and tissue damage in vivo. Here, we showed that, of the immune cell types tested, activated ?? T cells expressed the highest levels of A2AR mRNA and that A2AR ligation inhibited ?? T cell activation, but enhanced ?? T cell activation. We also showed that the inhibitory effect of an adenosine receptor agonist on autoreactive T cells was prevented by addition of a low percentage of activated ?? T cells. Furthermore, compared to resting cells, activated ?? T cells expressed significantly lower levels of CD73, an enzyme involved in the generation of extracellular adenosine. Exogenous AMP had a significant inhibitory effect on autoreactive T cell responses, but only in the presence of CD73+ ?? T cells, and this effect was abolished by a CD73 inhibitor. Our results show that expression of increased amounts of A2AR allows ?? T cells to bind adenosine and thereby attenuate its suppressive effect, while decreased expression of CD73 results in less generation of adenosine in the inflammatory site. Together, these events allow activated ?? T cells to acquire increased proinflammatory activity, leading to augmented autoimmune responses. PMID:25268760

Liang, Dongchun; Zuo, Aijun; Shao, Hui; Chen, Mingjiazi; Kaplan, Henry J.; Sun, Deming

2014-01-01

363

A ketogenic diet suppresses seizures in mice through adenosine A? receptors.  

PubMed

A ketogenic diet (KD) is a high-fat, low-carbohydrate metabolic regimen; its effectiveness in the treatment of refractory epilepsy suggests that the mechanisms underlying its anticonvulsive effects differ from those targeted by conventional antiepileptic drugs. Recently, KD and analogous metabolic strategies have shown therapeutic promise in other neurologic disorders, such as reducing brain injury, pain, and inflammation. Here, we have shown that KD can reduce seizures in mice by increasing activation of adenosine A1 receptors (A1Rs). When transgenic mice with spontaneous seizures caused by deficiency in adenosine metabolism or signaling were fed KD, seizures were nearly abolished if mice had intact A1Rs, were reduced if mice expressed reduced A1Rs, and were unaltered if mice lacked A1Rs. Seizures were restored by injecting either glucose (metabolic reversal) or an A1R antagonist (pharmacologic reversal). Western blot analysis demonstrated that the KD reduced adenosine kinase, the major adenosine-metabolizing enzyme. Importantly, hippocampal tissue resected from patients with medically intractable epilepsy demonstrated increased adenosine kinase. We therefore conclude that adenosine deficiency may be relevant to human epilepsy and that KD can reduce seizures by increasing A1R-mediated inhibition. PMID:21701065

Masino, Susan A; Li, Tianfu; Theofilas, Panos; Sandau, Ursula S; Ruskin, David N; Fredholm, Bertil B; Geiger, Jonathan D; Aronica, Eleonora; Boison, Detlev

2011-07-01

364

The Role of Ectonucleotidases CD39 and CD73 and Adenosine Signaling in Solid Organ Transplantation  

PubMed Central

Extracellular adenosine is a potent immunomodulatory molecule that accumulates in states of inflammation. Nucleotides such as adenosine triphosphate and adenosine diphosphate are release from injured and necrotic cells and hydrolyzed to adenosine monophosphate and adenosine by the concerted action of the ectonucleotidases CD39 and CD73. Accumulating evidence suggest that purinergic signaling is involved in the inflammatory response that accompanies acute rejection and chronic allograft dysfunction. Modification of the purinergic pathway has been shown to alter graft survival in a number of solid organ transplant models and the response to ischemia–reperfusion injury (IRI). Furthermore, the purinergic pathway is intrinsically involved in B and T cell biology and function. Although T cells have traditionally been considered the orchestrators of acute allograft rejection, a role for B cells in chronic allograft loss is being increasingly appreciated. This review focuses on the role of the ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation including the effects on IRI and T and B cell biology. PMID:24600452

Roberts, Veena; Stagg, John; Dwyer, Karen M.

2013-01-01

365

P2X7 receptor drives osteoclast fusion by increasing the extracellular adenosine concentration.  

PubMed

Defects in bone homeostasis are a major health problem. Osteoclast differentiation and activation have a crucial role in bone remodeling in health and disease. Osteoclasts are bone-resorbing cells derived from mononuclear phagocyte progenitors. The key event in osteoclast formation is fusion of mononucleate precursors to form mature multinucleated osteclasts. Here we provide evidence of an absolute requirement for the P2X7 receptor, ATP release, and adenosine signaling in human osteoclast formation, as shown by the following findings: macrophage-colony stimulating factor/receptor activator for nuclear factor-?B ligand (M-CSF/RANKL)-stimulated fusion of human monocytes is fully prevented by an anti-P2X7 mAb, by specific P2X7 pharmacological antagonists, or by inhibition of CD39/NTPDase; fusion-competent monocytes release ATP via the P2X7 receptor; accelerated degradation of released ATP by addition of either apyrase or hexokinase strongly increases fusion; removal of extracellular adenosine by adenosine deaminase blocks, while addition of exogenous adenosine strongly potentiates, fusion; and pharmacologic stimulation of the adenosine A2A receptor increases, while selective A2A blockade inhibits, fusion. These results show that the purinergic axis plays a crucial and as yet undescribed role in osteoclast formation and reconcile previous evidence advocating a key role for either ATP or adenosine receptors in multinucleated giant cell formation. PMID:21233486

Pellegatti, Patrizia; Falzoni, Simonetta; Donvito, Giovanna; Lemaire, Irma; Di Virgilio, Francesco

2011-04-01

366

Intravenous adenosine (adenoscan) versus exercise in the noninvasive assessment of coronary artery disease by SPECT  

SciTech Connect

Fifteen patients at a mean age of 58 underwent adenosine and maximal exercise thallium SPECT imaging. All scans were performed 1 week apart and within 4 weeks of cardiac catheterization. SPECT imaging was performed after the infusion of 140 micrograms/kg/min of adenosine for 6 minutes. Mean heart rate increment during adenosine administration was 67 +/- 3.7 to 77 +/- 4.1. Mean blood pressure was 136 +/- 7.2 to 135 +/- 6.2 systolic and 78 +/- 1.8 to 68 +/- 2.6 diastolic. No adverse hemodynamic effects were observed. There were no changes in PR or QRS in intervals. Five stress ECGs were ischemic. No ST changes were observed with adenosine. Although 68% of the patients had symptoms of flushing, light-headedness, and dizziness during adenosine infusion, symptoms resolved within 1 minute of dosage adjustment or termination of the infusion in all but one patient, who required theophylline. Sensitivity for coronary artery detection was 77% and specificity 100%. Concordance between adenoscans and exercise thallium scintigraphy was high (13/15 = 87%). In two patients, there were minor scintigraphic differences. The authors conclude that adenosine is a sensitive, specific, and safe alternative to exercise testing in patients referred for thallium imaging and may be preferable to dipyridamole.

LaManna, M.M.; Mohama, R.; Slavich, I.L. 3d.; Lumia, F.J.; Cha, S.D.; Rambaran, N.; Maranhao, V. (Deborah Heart and Lung Center, Browns Mills, NJ (USA))

1990-11-01

367

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells  

SciTech Connect

Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, the authors determined whether a 48-hr pretreatment with methotrexate affected adenosine release from ({sup 14}C)adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts. The effect of methotrexate on adenosine release was not due to cytotoxicity since cells treated with maximal concentrations of methotrexate took up ({sup 14}C)adenine and released {sup 14}C-labeled purine (a measure of cell injury) in a manner identical to control cells. Methotrexate treatment of fibroblasts dramatically inhibited adherence to fibroblasts by both unstimulated neutrophils and stimulated neutrophils. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, methotrexate induces the accumulation of AICAR, the nucleoside precursor of which has previously been shown to cause adenosine release from ischemic cardiac tissue. The observation that the antiinflammatory actions of methotrexate are due to the capacity of methotrexate to induce adenosine release may form the basis for the development of an additional class of antiinflammatory drugs.

Cronstein, B.N.; Eberle, M.A.; Levin, R.I. (New York Univ. Medical Center, New York (United States)); Gruber, H.E. (Gensia Pharmaceuticals, Inc., San Diego, CA (United States))

1991-03-15

368

Changes in adenosine sensitivity in the hippocampus of rats with streptozotocin-induced diabetes.  

PubMed Central

1. Hippocampal slices have been used to assess the sensitivity of the CNS to adenosine and gamma-aminobutyric acid (GABA) in diabetes. The effects of adenosine, 2-chloroadenosine, GABA, muscimol and baclofen were studied on orthodromic synaptic potentials recorded in the CA1 region of slices taken from normal rats or animals made diabetic by the injection of streptozotocin. 2. In diabetic animals the sensitivity to adenosine was increased 4 fold compared with normal rats. The potency of 2-chloroadenosine was unchanged. 3. The nucleoside transport inhibitor, hydroxynitrobenzylthioinosine (HNBTI), increased the potency of adenosine in slices from normal rats but not in slices from diabetic rats. 4. No change was observed in the potency of GABA or muscimol, although a small but significant decrease was detected in the EC50 value for baclofen. 5. Treatment of diabetic animals with insulin restored the potency of adenosine to control levels. 6. It is concluded that the diabetic state is accompanied by substantial changes of adenosine sensitivity due to the loss of nucleoside uptake processes. Secondary neurochemical changes following from this in human diabetic patients may contribute to the reported behavioural changes. PMID:1504709

Morrison, P. D.; Mackinnon, M. W.; Bartrup, J. T.; Skett, P. G.; Stone, T. W.

1992-01-01

369

Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist CF101  

Microsoft Academic Search

Adenosine is a purine nucleoside that acts as a regulatory molecule by binding to specific G-protein-coupled A1, A2A, A2B, and A3 cell surface receptors. We have recently demonstrated that adenosine inhibits tumour cell growth and concomitantly stimulates bone marrow cell proliferation via activation of the A3 adenosine receptor (A3AR). In the present study, we show that a synthetic agonist to

G Ohana; S Bar-Yehuda; A Arich; L Madi; Z Dreznick; L Rath-Wolfson; D Silberman; G Slosman; P Fishman

2003-01-01

370

The Role of Muscarinic Receptors in the Beneficial Effects of Adenosine against Myocardial Reperfusion Injury in Rats  

Microsoft Academic Search

Adenosine, a catabolite of ATP, displays a wide variety of effects in the heart including regulation of cardiac response to myocardial ischemia and reperfusion injury. Nonetheless, the precise mechanism of adenosine-induced cardioprotection is still elusive. Isolated Sprague-Dawley rat hearts underwent 30 min global ischemia and 120 min reperfusion using a Langendorff apparatus. Both adenosine and acetylcholine treatment recovered the post-reperfusion

Lei Sun; Dong-Ling Li; Mei Zhao; Xi He; Xiao-Jiang Yu; Yi Miao; Hao Wang; Jun Ren; Wei-Jin Zang

2011-01-01

371

A comparison of the adenosine-mediated synaptic inhibition in the CA3 area of immature and adult rat hippocampus  

Microsoft Academic Search

We compared the effects of the adenosine A1 receptor activation on the postsynaptic potentials (psps) recorded from the CA3 area of immature (postnatal days 10–20) and adult rat hippocampal neurons in vitro. The adenosine A1 receptor agonist 2-phenyl-isopropyl-adenosine (PIA, 1 ?M) depressed the stimulus-induced psps less in immature and more in adult neurons. In the presence of the GABAA receptor

Severine Descombes; Massimo Avoli; Caterina Psarropoulou

1998-01-01

372

Accumulation of adenosine 3?,5? -monophosphate in slices of rat cerebral cortex induced by alpha-adrenergic agonists  

Microsoft Academic Search

Incubation of slices of rat cerebral cortex with the calcium ionophore A23187 produced small increases in the accumulation of adenosine 3',5'-monophosphate (cyclic AMP). While low concentrations of Ca2+ ions (e.g., 200 µM) were sometimes necessary, the presence of adenosine (e.g., 50 µM) was essential; no effect of ionophore was observed when isoproterenol or isobutylmethylxanthine was substituted for adenosine. These results

D. R. O'Brien; T. W. Rall

1987-01-01

373

Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study  

Microsoft Academic Search

Previous data suggested that increases in extracellular adenosine in the basal forebrain mediated the sleep-inducing effects of prolonged wakefulness. The present study sought to determine if the state-related changes found in basal forebrain adenosine levels occurred uniformly throughout the brain. In vivo microdialysis sample collection coupled to microbore high-performance liquid chromatography measured extracellular adenosine levels in six brain regions of

T Porkka-Heiskanen; R. E Strecker; R. W McCarley

2000-01-01

374

Cyclic Adenosine 3?:5?-Monophosphate in Moss Protonema  

PubMed Central

From the protonema of the moss Funaria hygrometrica (L.) Sibth, a factor indistinguishable from cyclic adenosine 3?:5?-monophosphate (cAMP) has been isolated. The factor stimulated the activity of protein kinase from rabbit skeletal muscle and co-chromatographed with authentic cAMP in two solvent systems. Its ability to stimulate protein kinase activity was completely abolished by 3?:5?-cyclic nucleotide phosphodiesterase, the rate of inactivation being similar to that of authentic cAMP. Based on these properties, this factor is identified as 3?,5?-cAMP. Cyclic AMP could be readily removed from the cells and washing the cells with water reduced the endogenous level of cAMP by 2- to 3-fold. A comparison of cAMP levels by protein kinase and Gilman assays was made. The intracellular levels determined by protein kinase assay were about 7-fold lower than the values obtained by Gilman assay. This discrepancy was due to the presence of unidentified compounds which were completely degraded by 3?:5?-cyclic nucleotide phosphodiesterase. Although these displaced labeled cAMP in the Gilman assay, they did not stimulate the protein kinase activity. The protonema may contain cyclic nucleotides other than cAMP; these will not be detected in the protein kinase assay due to the specificity of this reaction. The crude extracts were found to be unsuitable for assaying cAMP by either method. PMID:16659878

Handa, Avtar Krishan; Johri, Man Mohan

1977-01-01

375

Plasma adenosine deaminase isoform 2 in cancer patients undergoing chemotherapy.  

PubMed

Adenosine deaminase (AD), a purine salvage enzyme, exists as AD isoform 1 (AD1) and AD isoform 2 (AD2). Plasma AD has been advocated for the screening and monitoring of cancer, as AD2 activity is increased in conditions associated with tumour growth. Plasma AD2 was measured before and seven to 10 days after the first dose of chemotherapy in patients with different tumours. A 'tumour regression score' was assessed independently based on radiological changes seen in the tumour following completion of chemotherapy. Changes in plasma AD2 were then compared with the tumour regression score. Following first-dose chemotherapy, plasma AD2 decreased on average from 22.7 +/- 10.5 U/L to 15.0 +/- 4.6 U/L. The percentage decrease in plasma AD2 correlated with the tumour regression score (r=0.5, P=0.028). These data suggest plasma AD2 may have a role in determining tumour response to treatment. PMID:22558798

Roberts, E L; Roberts, O T

2012-01-01

376

Targeting the A3 adenosine receptor for glaucoma treatment (review).  

PubMed

Glaucoma is a worldwide disease and the second leading cause of blindness. Current treatments are associated with a number of side-effects and poor compliance, due to the requirement for treatment administration several times a day. These treatments typically aim to lower intraocular pressure (IOP); however, they are unable to protect retinal ganglion cells (RGCs) from undergoing apoptosis, which is the main cause of vision loss. A3 adenosine receptor (A3AR) agonists have been found to protect normal cells from undergoing apoptosis via the downregulation of death signals. Furthermore, A3AR agonists have been reported to have several ophthalmological effects, including the prevention of ganglion cell apoptosis in vitro and in vivo and anti?inflammatory effects in experimental models of autoimmune uveitis. CF101, an orally bioavailable A3AR agonist, has been analyzed in dry eye syndrome phase II clinical trials and was identified to be safe and well tolerated. The anti?inflammatory effect of CF101 was shown to significantly improve corneal staining, tear meniscus and tear break?up time in dry eye patients. In addition, CF101 was found to decrease IOP in patients. The safety and efficacy of CF101, together with its suitability for oral administration, indicates that it has potential as a candidate drug for the treatment of glaucoma. PMID:23563604

Fishman, Pnina; Cohen, Shira; Bar-Yehuda, Sara

2013-06-01

377

ADA (adenosine deaminase) gene therapy enters the competition  

SciTech Connect

Around the world, some 70 children are members of a select and deadly club. Born with an immune deficiency so severe that they will die of infection unless their immune systems can be repaired, they have captured the attention of would-be gene therapists who believe that a handful of these kids--the 15 or 20 who lack functioning levels of the enzyme adenosine deaminase (ADA)--could be saved by a healthy ADA gene. A team of gene therapists is ready to put the theory to the test. In April 1987, a team of NIH researchers headed by R. Michael Blaese and W. French Anderson came up with the first formal protocol to introduce a healthy ADA gene into an unhealthy human. After 3 years of line-by-line scrutiny by five review committees, they have permission to go ahead. Two or three children will be treated in the next year, and will be infused with T lymphocytes carrying the gene for ADA. If the experiment works, the ADA gene will begin producing normal amounts of ADA. An interesting feature of ADA deficiency, that makes it ideal for initial gene studies, is that the amount of ADA one needs for a healthy immune system is quite variable. Hence, once inside a patient's T cells, the new ADA gene needs only to express the enzyme in moderate amounts. No precise gene regulation is necessary.

Culliton, B.J.

1990-08-31

378

Apoptosis induced by adenosine in human leukemia HL-60 cells.  

PubMed

Among several nucleosides and nucleotides, which showed strong inhibition of growth of HL-60 cells, only adenosine (Ado) specifically induced typical apoptotic death of the cells, accompanying double-strand cleavage of DNA into nucleosomal size fragments, and subsequent apoptotic body formation. A marked enhancement of endogenous poly(ADP-ribosyl)ation activity in the cell was detected at a relatively early stage of cell death, whereas other nucleosides and nucleotides tested were ineffective on poly(ADP-ribosyl)ation activity, suggesting that the enzyme activation is closely related to apoptosis. The observed Ado effect was not mediated by Ado receptors, in contrast to the Ado-induced apoptotic death of thymocytes, judging from the facts that all of the receptor agonists tested did not substitute for Ado and that a receptor antagonist did not inhibit the effect of Ado. Ado transport into the cell seemed to be essential for the induction of apoptosis, since an inhibitor of Ado transport (dipyridamole) strongly suppressed apoptosis. Cytochalasin B blocked Ado-induced apoptotic body formation without affecting activation of endogenous poly(ADP-ribosyl)ation activity in the cell. Thus, the process of apoptosis in HL-60 cells induced by Ado seems to be separated into at least two steps, an initial step of DNA degradation and a following morphological change. While the adenine moiety of Ado was essential for its apoptosis-inducing activity, the sugar was replaceable, and various analogs with modified sugar were inducers of apoptosis, although they were less efficient than Ado. PMID:8020596

Tanaka, Y; Yoshihara, K; Tsuyuki, M; Kamiya, T

1994-07-01

379

Structure-Activity Relationships of 2,N6,5?-Substituted Adenosine Derivatives with Potent Activity at the A2B Adenosine Receptor  

PubMed Central

2, N6, and/or 5? substituted adenosine derivatives were synthesized via alkylation of 2-oxypurine nucleosides leading to 2-aralkylether derivatives. 2-(3-(Indolyl)ethyloxy)adenosine 17 was found to be a potent agonist of the human A2BAR in both binding and cAMP assays. Simplification, altered connectivity and mimicking of the indole ring of 17 failed to maintain A2BAR potency. Introduction of N6-ethyl or N6-guanidino substitution, shown to favor A2BAR potency, failed to enhance potency in the 2-(3-(indolyl)ethyloxy)adenosine series. Indole 5?- or 6?-halo substitution was favored at the A2BAR, but a 5?-N-ethylcarboxyamide did not further enhance potency. 2-(3?-(6?-Bromoindolyl)ethyloxy)adenosine 28 displayed an A2BAR EC50 value (nM) of 128, i.e. more potent than the parent 17 (299) and similar to 5?-N-ethylcarboxamidoadenosine (140). 28 was a full agonist at A2B and A2AARs and a low efficacy partial agonist at A1 and A3ARs. Thus, we have identified and optimized 2-(2-arylethyl)oxo moieties in AR agonists that enhance A2BAR potency and selectivity. PMID:17378544

Adachi, Hayamitsu; Palaniappan, Krishnan K.; Ivanov, Andrei A.; Bergman, Nathaniel; Gao, Zhan-Guo; Jacobson, Kenneth A.

2012-01-01

380

Role of endogenous adenosine in the acute and late response to allergen challenge in actively sensitized Brown Norway rats  

PubMed Central

Endogenous adenosine has been suggested to amplify the response of airway mast cells to allergen in vivo. We have sought evidence for this by monitoring the acute and late-phase response to allergen in Brown Norway (BN) rats actively sensitised to ovalbumin (OA) and treated either with adenosine deaminase (ADA) linked covalently to polyethylene glycol (PEG-ADA; Adagen®) to decrease adenosine availability or with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an inhibitor of ADA, plus S-(4-nitrobenzyl)-6-thioinosine (NBTI), an inhibitor of facilitated adenosine transport, to increase adenosine availability. The cardiovascular effects of adenosine (0.01–3 mg kg?1 i.v.) were significantly reduced in PEG-ADA-treated animals and augmented in EHNA/NBTI-treated animals. The difference in sensitivity to adenosine in the treated groups was 33- and 15-fold, at the level of 30% reduction in blood pressure and heart rate, respectively. The acute response to allergen, given either intravenously or intratracheally, was quantified as bronchoconstriction. The late phase to allergen was measured as the influx and activation of immunoinflammatory cells into the bronchoalveolar lavage fluid 24 h after challenge. Despite evidence of a substantial difference in adenosine availability following pretreatment with PEG-ADA or EHNA/NBTI, there were no differences in either the acute or late response to allergen in the actively sensitised BN rat. Our data suggest no role for endogenous adenosine in determining the response to allergen under our experimental conditions. PMID:12871841

Ellis, K M; Mazzoni, L; Fozard, J R

2003-01-01

381

Fluorometric Determination of Adenosine Nucleotide Derivatives as Measures of the Microfouling, Detrital, and Sedimentary Microbial Biomass and Physiological Status  

PubMed Central

Adenosine, adenine, cyclic adenosine monophosphate (AMP), AMP, nicotinamide adenine dinucleotide, adenosine diphosphate, and adenosine triphosphate (ATP) were recovered quantitatively from aqueous portions of lipid extracts of microfouling, detrital, and sedimentary microbial communities. These could be detected quantitatively in the picomolar range by forming their 1-N6-etheno derivatives and analyzing by high-pressure liquid chromatography with fluorescence detection. Lipid extraction and subsequent analysis allowed the simultaneous measurement of the microbial community structure, total microbial biomass with the quantitative recovery of the adenine-containing cellular components, which were protected from enzymatic destruction. This extraction and fluorescent derivatization method showed equivalency with the luciferin-luciferase method for bacterial ATP measurements. Quick-freezing samples in the field with dry ice-acetone preserved the ATP and energy charge (a ratio of adenosine nucleotides) for analysis at remote laboratories. The metabolic lability of ATP in estuarine detrital and microfouling communities, as well as bacterial monocultures of constant biomass, showed ATP to be a precarious measure of biomass under some conditions. Combinations of adenosine and adenine nucleotides gave better correlations with microbial biomass measured as extractable lipid phosphate in the detrital and microfouling microbial communities than did ATP alone. Stresses such as anoxia or filtration are reflected in the rapid accumulation of intracellular adenosine and the excretion of adenosine and AMP into the surrounding milieu. Increases in AMP and adenosine may prove to be more sensitive indicators of metabolic status than the energy charge. PMID:16345633

Davis, William M.; White, David C.

1980-01-01

382

Inhibition of Platelet Activation and Thrombus Formation by Adenosine and Inosine: Studies on Their Relative Contribution and Molecular Modeling  

PubMed Central

Background The inhibitory effect of adenosine on platelet aggregation is abrogated after the addition of adenosine-deaminase. Inosine is a naturally occurring nucleoside degraded from adenosine. Objectives The mechanisms of antiplatelet action of adenosine and inosine in vitro and in vivo, and their differential biological effects by molecular modeling were investigated. Results Adenosine (0.5, 1 and 2 mmol/L) inhibited phosphatidylserine exposure from 52±4% in the control group to 44±4 (p<0.05), 29±2 (p<0.01) and 20±3% (p<0.001). P-selectin expression in the presence of adenosine 0.5, 1 and 2 mmol/L was inhibited from 32±4 to 27±2 (p<0.05), 14±3 (p<0.01) and 9±3% (p<0.001), respectively. At the concentrations tested, only inosine to 4 mmol/L had effect on platelet P-selectin expression (p<0.05). Adenosine and inosine inhibited platelet aggregation and ATP release stimulated by ADP and collagen. Adenosine and inosine reduced collagen-induced platelet adhesion and aggregate formation under flow. At the same concentrations adenosine inhibited platelet aggregation, decreased the levels of sCD40L and increased intraplatelet cAMP. In addition, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent adenosine receptor A2A antagonist) attenuated the effect of adenosine on platelet aggregation induced by ADP and intraplatelet level of cAMP. Adenosine and inosine significantly inhibited thrombosis formation in vivo (62±2% occlusion at 60 min [n?=?6, p<0.01] and 72±1.9% occlusion at 60 min, [n?=?6, p<0.05], respectively) compared with the control (98±2% occlusion at 60 min, n?=?6). A2A is the adenosine receptor present in platelets; it is known that inosine is not an A2A ligand. Docking of adenosine and inosine inside A2A showed that the main difference is the formation by adenosine of an additional hydrogen bond between the NH2 of the adenine group and the residues Asn253 in H6 and Glu169 in EL2 of the A2A receptor. Conclusion Therefore, adenosine and inosine may represent novel agents lowering the risk of arterial thrombosis. PMID:25393959

Fuentes, Eduardo; Pereira, Jaime; Mezzano, Diego; Alarcón, Marcelo; Caballero, Julio; Palomo, Iván

2014-01-01

383

Recombinant AAV-Mediated Gene Transfer for the Potential Therapy of Adenosine Deaminase Deficient Severe Combined Immune Deficiency.  

E-print Network

??Adenosine deaminase (ADA) deficiency fosters a rare, but devastating pediatric severe combined immune deficiency (SCID) with a T- B- NK- phenotype, concomitant opportunistic infections including… (more)

Silver, Jared

2008-01-01

384

Adenosine Receptors and the Heart: Role in Regulation of Coronary Blood Flow and Cardiac Electrophysiology  

PubMed Central

Adenosine is an autacoid that plays a critical role in regulating cardiac function, including heart rate, contractility, and coronary flow. In this chapter, current knowledge of the functions and mechanisms of action of coronary flow regulation and electrophysiology will be discussed. Currently, there are four known adenosine receptor (AR) subtypes, namely A1, A2A, A2B, and A3. All four subtypes are known to regulate coronary flow. In general, A2AAR is the predominant receptor subtype responsible for coronary blood flow regulation, which dilates coronary arteries in both an endothelial-dependent and -independent manner. The roles of other ARs and their mechanisms of action will also be discussed. The increasing popularity of gene-modified models with targeted deletion or overexpression of a single AR subtype has helped to elucidate the roles of each receptor subtype. Combining pharmacologic tools with targeted gene deletion of individual AR subtypes has proven invaluable for discriminating the vascular effects unique to the activation of each AR subtype. Adenosine exerts its cardiac electrophysiologic effects mainly through the activation of A1AR. This receptor mediates direct as well as indirect effects of adenosine (i.e., anti-?-adrenergic effects). In supraventricular tissues (atrial myocytes, sinua-trial node and atriovetricular node), adenosine exerts both direct and indirect effects, while it exerts only indirect effects in the ventricle. Adenosine exerts a negative chronotropic effect by suppressing the automaticity of cardiac pacemakers, and a negative dromotropic effect through inhibition of AV-nodal conduction. These effects of adenosine constitute the rationale for its use as a diagnostic and therapeutic agent. In recent years, efforts have been made to develop A1R-selective agonists as drug candidates that do not induce vasodilation, which is considered an undesirable effect in the clinical setting. PMID:19639282

Morrison, R. Ray; Teng, Bunyen; Pelleg, Amir

2010-01-01

385

[Fast determination of adenosine and cordycepin in Cordyceps and its deserted solid medium].  

PubMed

A fast analytical method for adenosine and cordycepin in Cordyceps and its deserted solid medium was developed by using a normal-phase cyan-group chromatographic column. The sample was extracted for 1.5 min using a microwave-assisted extraction system. The extraction was repeated twice. The analysis of adenosine and cordycepin was performed on an Eclipse XDB-CN column. The mobile phase was composed of methanol and water with a ratio of 7:93 (v/v) for isocratic elution. The detection wavelength was 260 nm. The composition and pH value of the mobile phase were investigated. The results showed that adenosine and cordycepin could be completely separated without matrix interference in 4.5 min. The linearity of the method was good with a linear correlation coefficient (r2) of 0. 999 8 for adenosine and 0.999 5 for cordycepin. The limits of quantification (LOQs, S/N = 10) of adenosine and cordycepin were 0.21 and 0.083 mg/L, respectively. The relative standard deviations (RSDs) of peak areas of six replicate injections were less than 2% both for intra-day and inter-day analysis. The average recoveries of adenosine and cordycepin ranged from 93.8% to 102.9% with the RSD not more than 3.62% (n = 5). The developed method is simple, fast, accurate and low-cost, and it can be used in the fast detection of adenosine and cordycepin in Cordyceps, carpohole, the deserted solid medium and its praeparatum. PMID:23189667

Li, Chen; Yan, Aiguo; Cai, Chunyan; Liu, Zhiping

2012-07-01

386

Contribution of adenosine to isoproterenol-stimulated prostacyclin production in rabbit heart.  

PubMed

This study investigated adenosine's contribution to isoproterenol-stimulated prostacyclin production, measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output, and mechanical function in the isolated rabbit heart perfused with Krebs-Henseleit buffer. The isoproterenol-induced increase in 6-keto-PGF1 alpha was diminished by adenosine (10 microM), the A1 receptor antagonist 1,3-dipropyl, 8-cyclopentylxanthine (DPCPX 0.06 microM), and the A2 receptor agonist CGS-21680 (0.6 microM); CGS-21680 did not decrease heart rate (HR) or myocardial contractility (dP/dt(max)). The isoproterenol-induced increase in 6-keto-PGF1 alpha was potentiated by the A1 receptor agonist 1-deaza,2-chloro,N6-cyclopentyladenosine (DCCA, 0.6 microM) and the A2 receptor antagonist 3,7-dimethyl,1-propargylxanthine (DMPX, 6 microM). The isoproterenol-induced increase in dP/dt(max) and HR was diminished by adenosine, DCCA, and DMPX. DPCPX enhanced dP/dt(max) and HR and prevented the decrease by adenosine and DCCA of the isoproterenol-induced increase in HR and dP/dt(max); the increase by DCCA but not the decrease by adenosine in 6-keto-PGF1 alpha output was abolished. DMPX abolished the effect of adenosine and CGS-21680 to reduce isoproterenol-stimulated 6-keto-PGF1 alpha. These data suggest that adenosine generated in response to isoproterenol attenuates its effect on HR and dP/dt(max) through A1 receptors and on prostacyclin synthesis via A2 receptors. PMID:1636761

Cano, C; Qureshi, Z; Carter, S; Malik, K U

1992-07-01

387

Orexin A attenuates the sleep-promoting effect of adenosine in the lateral hypothalamus of rats.  

PubMed

Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regulated sleep homeostasis. Orexin A induces a robust increase in the firing activity of orexin neurons, while adenosine has an inhibitory effect. Whether the excitatory action of orexins in the lateral hypothalamus actually promotes wakefulness and reverses the sleep-producing effect of adenosine in vivo is less clear. In this study, electroencephalographic and electromyographic recordings were used to investigate the effects of orexin A and adenosine on sleep and wakefulness in rats. We found that microinjection of orexin A into the lateral hypothalamus increased wakefulness with a concomitant reduction of sleep during the first 3 h of post-injection recording, and this was completely blocked by a selective antagonist for orexin receptor 1, SB 334867. The enhancement of wakefulness also occurred after application of the excitatory neurotransmitter glutamate in the first 3 h post-injection. However, in the presence of the NMDA receptor antagonist APV, orexin A did not induce any change of sleep and wakefulness in the first 3 h. Further, exogenous application of adenosine into the lateral hypothalamus induced a marked increase of sleep in the first 3-h post-injection. No significant change in sleep and wakefulness was detected after adenosine application followed by orexin A administration into the same brain area. These findings suggest that the sleep-promoting action of adenosine can be reversed by orexin A applied to the lateral hypothalamus, perhaps by exciting glutamatergic input to orexin neurons via the action of orexin receptor 1. PMID:24898402

Cun, Yanping; Tang, Lin; Yan, Jie; He, Chao; Li, Yang; Hu, Zhian; Xia, Jianxia

2014-10-01

388

CD73+ regulatory T cells contribute to adenosine-mediated resolution of acute lung injury  

PubMed Central

Acute lung injury (ALI) is characterized by alveolar injury and uncontrolled inflammation. Since most cases of ALI resolve spontaneously, understanding the endogenous mechanisms that promote ALI resolution is important to developing effective therapies. Previous studies have implicated extracellular adenosine signaling in tissue adaptation and wound healing. Therefore, we hypothesized a functional contribution for the endogenous production of adenosine during ALI resolution. As a model, we administered intratracheal LPS and observed peak lung injury at 3 d, with resolution by d 14. Treatment with pegylated adenosine-deaminase to enhance extracellular adenosine breakdown revealed impaired ALI resolution. Similarly, genetic deletion of cd73, the pacemaker for extracellular adenosine generation, was associated with increased mortality (0% wild-type and 40% in cd73?/? mice; P<0.05) and failure to resolve ALI adequately. Studies of inflammatory cell trafficking into the lungs during ALI resolution revealed that regulatory T cells (Tregs) express the highest levels of CD73. While Treg numbers in cd73?/? mice were similar to controls, cd73-deficient Tregs had attenuated immunosuppressive functions. Moreover, adoptive transfer of cd73-deficient Tregs into Rag?/? mice emulated the observed phenotype in cd73?/? mice, while transfer of wild-type Tregs was associated with normal ALI resolution. Together, these studies implicate CD73-dependent adenosine generation in Tregs in promoting ALI resolution.—Ehrentraut, H., Clambey, E. T., McNamee, E. N., Brodsky, K. S., Ehrentraut, S. F., Poth, J. M., Riegel, A. K., Westrich, J. A., Colgan, S. P., Eltzschig, H. K. CD73+ regulatory T cells contribute to adenosine-mediated resolution of acute lung injury. PMID:23413361

Ehrentraut, Heidi; Clambey, Eric T.; McNamee, Eoin N.; Brodsky, Kelley S.; Ehrentraut, Stefan F.; Poth, Jens M.; Riegel, Ann K.; Westrich, Joseph A.; Colgan, Sean P.; Eltzschig, Holger K.

2013-01-01

389

Differential Coronary Microvascular Exchange Responses to Adenosine: Roles of Receptor and Microvessel Subtypes  

PubMed Central

Objective To assess the role of adenosine receptors in the regulation of coronary microvascular permeability to porcine serum albumin (PsPSA). Methods Solute flux was measured in single perfused arterioles and venules isolated from pig hearts using fluorescent dye-labeled probes by microspectro-fluorometry. Messenger RNA, protein, and cellular distribution of adenosine receptors in arterioles and venules were analyzed by RT-PCR, immunoblot, and immunofluorescence. Results Control venule PsPSA (10.7 ± 4.8 × 10?7 cm s?1) was greater than that of arterioles (6.4 ± 2.8 × 10?7 cm · s?1; p <.05). Arteriolar PsPSA decreased ( p <.05) with adenosine suffusion over the range from 10?8 to 10?5 M, while venular PsPSA did not change. The nonselective A1 and A2 receptor antagonist, 8-(p-sulfophenyl) theophylline, blocked the adenosine-induced decrease in arteriolar PsPSA. Messenger RNA for adenosine A1,A2A,A2B, and A3 receptors was expressed in arterioles and venules. Protein for A1, A2A, and A2B, but not A3, was detected in both microvessel types and was further demonstrated on vascular endothelial cells. Conclusion Arteriolar PsPSA decreases with adenosine suffusion but not venular PsPSA. Adenosine A1, A2A, and A2B receptors are expressed in both arterioles and venules. Selective receptor-linked cellular signaling mechanisms underlying the regulation of permeability remain to be determined. PMID:16020078

WANG, JIANJIE; WHITT, STEVAN P.; RUBIN, LEONA J.; HUXLEY, VIRGINIA H.

2012-01-01

390

Evidence for adenosine mediation of atrioventricular block in the ischemic canine myocardium.  

PubMed Central

Adenosine levels in oxygen-deprived myocardium can rise to 10- 100 microM concentrations known to cause atrioventricular (AV) conduction delay and block. We reported that the AV conduction delay and block caused by hypoxia is markedly attenuated by 10 microM aminophylline, and adenosine competitive antagonist. THe purpose of the present study was to investigate adenosine's role in ischemic AV conduction disturbances. Dogs were anesthetized and instrumented for His bundle and surface electrogram recordings. The total AV conduction time was subdivided in to atrial-His bundle (AH) and His bundle-ventricle intervals. The atrioventricular node artery (AVNA) was cannulated for selective injection of drugs in the AV node region. Adenosine (10 to 100 microgram), as a 2-ml bolus injection, rapidly produced a dose-dependent, transient increase in the AH interval; a 1,000-microgram dose caused second degree AV block. The duration of the increase in AH interval was also dose-dependent. Dipyridamole, and inhibitor of nucleoside transport, potentiated the negative dromotropic effects of adenosine, whereas aminophylline attenuated them. In some dogs, after cannulation of the AVNA, first and second degree AV block occurred spontaneously or were induced by rapid atrial pacing. Injection of the aminophylline (5 mg/kg, i.e.) or theophylline (100-1,000 microgram) into the AVNA rapidly reversed the AV blocks. Upon washout of the drugs the AV blocks recurred. We conclude that endogenously released adenosine may account for a major fraction of the AV conduction delay and block associated with impaired blood supply to the AV node, and the theophylline and aminophylline reverse the AV conduction defect by antagonizing the effects of adenosine. PMID:7251860

Belardinelli, L; Mattos, E C; Berne, R M

1981-01-01

391

The Metal Ion-Dependent Adhesion Site Motif of the Enterococcus faecalis EbpA Pilin Mediates Pilus Function in Catheter-Associated Urinary Tract Infection  

PubMed Central

ABSTRACT Though the bacterial opportunist Enterococcus faecalis causes a myriad of hospital-acquired infections (HAIs), including catheter-associated urinary tract infections (CAUTIs), little is known about the virulence mechanisms that it employs. However, the endocarditis- and biofilm-associated pilus (Ebp), a member of the sortase-assembled pilus family, was shown to play a role in a mouse model of E. faecalis ascending UTI. The Ebp pilus comprises the major EbpC shaft subunit and the EbpA and EbpB minor subunits. We investigated the biogenesis and function of Ebp pili in an experimental model of CAUTI using a panel of chromosomal pilin deletion mutants. A nonpiliated pilus knockout mutant (EbpABC? strain) was severely attenuated compared to its isogenic parent OG1RF in experimental CAUTI. In contrast, a nonpiliated ebpC deletion mutant (EbpC? strain) behaved similarly to OG1RF in vivo because it expressed EbpA and EbpB. Deletion of the minor pilin gene ebpA or ebpB perturbed pilus biogenesis and led to defects in experimental CAUTI. We discovered that the function of Ebp pili in vivo depended on a predicted metal ion-dependent adhesion site (MIDAS) motif in EbpA’s von Willebrand factor A domain, a common protein domain among the tip subunits of sortase-assembled pili. Thus, this study identified the Ebp pilus as a virulence factor in E. faecalis CAUTI and also defined the molecular basis of this function, critical knowledge for the rational development of targeted therapeutics. PMID:22829678

Nielsen, Hailyn V.; Guiton, Pascale S.; Kline, Kimberly A.; Port, Gary C.; Pinkner, Jerome S.; Neiers, Fabrice; Normark, Staffan; Henriques-Normark, Birgitta; Caparon, Michael G.; Hultgren, Scott J.

2012-01-01

392

Artificial oxygen carrier with pharmacologic actions of adenosine-5'-triphosphate, adenosine, and reduced glutathione formulated to treat an array of medical conditions.  

PubMed

Effective artificial oxygen carriers may offer a solution to tackling current transfusion medicine challenges such as blood shortages, red blood cell storage lesions, and transmission of emerging pathogens. These products, could provide additional therapeutic benefits besides oxygen delivery for an array of medical conditions. To meet these needs, we developed a hemoglobin (Hb)-based oxygen carrier, HemoTech, which utilizes the concept of pharmacologic cross-linking. It consists of purified bovine Hb cross-linked intramolecularly with open ring adenosine-5'-triphosphate (ATP) and intermolecularly with open ring adenosine, and conjugated with reduced glutathione (GSH). In this composition, ATP prevents Hb dimerization, and adenosine promotes formation of Hb polymers as well as counteracts the vasoconstrictive and pro-inflammatory properties of Hb via stimulation of adenosine receptors. ATP also serves as a regulator of vascular tone through activation of purinergic receptors. GSH blocks Hb's extravasation and glomerular filtration by lowering the isoelectric point, as well as shields heme from nitric oxide and reactive oxygen species. HemoTech and its manufacturing technology have been broadly tested, including viral and prion clearance validation studies and various nonclinical pharmacology, toxicology, genotoxicity, and efficacy tests. The clinical proof-of-concept was carried out in sickle cell anemia subjects. The preclinical and clinical studies indicate that HemoTech works as a physiologic oxygen carrier and has efficacy in treating: (i) acute blood loss anemia by providing a temporary oxygen bridge while stimulating an endogenous erythropoietic response; (ii) sickle cell disease by counteracting vaso-occlusive/inflammatory episodes and anemia; and (iii) ischemic vascular diseases particularly thrombotic and restenotic events. The pharmacologic cross-linking of Hb with ATP, adenosine, and GSH showed usefulness in designing an artificial oxygen carrier for multiple therapeutic indications. PMID:24980041

Simoni, Jan; Simoni, Grace; Moeller, John F; Feola, Mario; Wesson, Donald E

2014-08-01

393

Intermittent aortic crossclamping prevents cumulative adenosine triphosphate depletion, ventricular fibrillation, and dysfunction (stunning): is it preconditioning?  

PubMed

This study was designed to determine whether intermittent warm aortic crossclamping induces cumulative myocardial stunning or if the myocardium becomes preconditioned after the first episode of ischemia in canine models in vivo. The role of adenosine triphosphate catabolism and subsequent release of purines on reperfusion-mediated postischemic ventricular dysfunction and arrhythmias was assessed with the use of selective inhibitors of nucleoside transport, p-nitrobenzylthioinosine (NBMPR), and a specific adenosine deaminase inhibitor, erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA). Thirty-two anesthetized dogs were instrumented to monitor left ventricular contractility, off bypass, by sonomicrometry. During cardiopulmonary bypass dogs were treated before ischemia with either saline solution (control group, n = 8) or EHNA (100 mumol/L) and NBMPR (25 mumol/L) (EHNA/NBMPR group, n = 8). Hearts were subjected to either 60 minutes of global ischemia and 120 minutes of reperfusion (n = 16) or 6 episodes of 10 minutes of global ischemia and 10 minutes of reperfusion, followed by 60 minutes of reperfusion (n = 16). Sixty minutes of sustained ischemia resulted in 80% loss of adenosine triphosphate and induced reperfusion-mediated ventricular fibrillation and severe left ventricular dysfunction in the control group. EHNA/NBMPR treatment augmented myocardial adenosine trapping during ischemia, attenuated ventricular fibrillation, and enhanced left ventricular functional recovery, despite similar depletion of adenosine triphosphate (80% loss). In the intermittent ischemia experiment, the first episode of 10 minutes of ischemia and reperfusion caused significant adenosine triphosphate depletion, ventricular fibrillation, and left ventricular stunning in both control and drug-treated groups. The prevalence of ventricular fibrillation was greater in the control group than in the drug-treated group after the first episode of ischemia (p < 0.05). Adenosine was the major nucleoside accumulated in the myocardium at the end of 10 minutes of ischemia in the EHNA/NBMPR-treated group (p < 0.05 versus control). Subsequent episodes of ischemia prevented ventricular fibrillation and did not cause cumulative left ventricular stunning in either group. Left ventricular function fully recovered in the EHNA/NBMPR-treated group after intermittent ischemia, but remained stunned in the control group. Unlike sustained ischemia, intermittent ischemia and reperfusion preserved myocardial adenosine triphosphate, limited purine release, and prevented ventricular fibrillation and cumulative stunning. These results suggest that intermittent ischemia and reperfusion augmented the endogenous protective mechanism or mechanisms of "preconditioning." Nucleoside trapping improved functional recovery after sustained or repetitive ischemia. It is concluded that adenosine triphosphate preservation or blockade of nucleoside transport may play an important role in the activation of endogenous myocardial protective mechanisms that "precondition" against subsequent ischemic stress. PMID:7637350

Abd-Elfattah, A S; Ding, M; Wechsler, A S

1995-08-01

394

Modulation of Adenosine Receptors by [60]Fullerene Hydrosoluble Derivative in SK-N-MC Cells  

PubMed Central

The most known fullerenes are spherical carbon compounds composed of 60 carbon atoms. C60 fullerenes have shown biochemical and biomedical properties in the last years such as as blockade of apoptosis and neuroprotection. The nucleoside adenosine has a neuroprotective role mainly due to inhibition of glutamate release, which is a neurotransmitter related to excitotoxicity and cell death. In the present work, we have determined the presence of adenosine receptors in SK-N-MC cells, a neuroepithelioma human cell line, and analyzed the effect of fullerenes in these receptors by using radioligand binding, immunoblotting, and quantitative real time PCR assays. Results demonstrated that SK-N-MC cells endogenously express adenosine receptors. Fullerene exposure of these cells did not affect cell viability measured by MTT reduction assay. However, adenosine A1 and A2A receptors were both increased in SK-N-MC cells after treatment. These results suggest for the first time the modulation of adenosine receptors after C60 fullerenes exposure. PMID:22816023

2011-01-01

395

Modulation of adenosine receptors by [60]fullerene hydrosoluble derivative in SK-N-MC cells.  

PubMed

The most known fullerenes are spherical carbon compounds composed of 60 carbon atoms. C(60) fullerenes have shown biochemical and biomedical properties in the last years such as as blockade of apoptosis and neuroprotection. The nucleoside adenosine has a neuroprotective role mainly due to inhibition of glutamate release, which is a neurotransmitter related to excitotoxicity and cell death. In the present work, we have determined the presence of adenosine receptors in SK-N-MC cells, a neuroepithelioma human cell line, and analyzed the effect of fullerenes in these receptors by using radioligand binding, immunoblotting, and quantitative real time PCR assays. Results demonstrated that SK-N-MC cells endogenously express adenosine receptors. Fullerene exposure of these cells did not affect cell viability measured by MTT reduction assay. However, adenosine A(1) and A(2A) receptors were both increased in SK-N-MC cells after treatment. These results suggest for the first time the modulation of adenosine receptors after C(60) fullerenes exposure. PMID:22816023

Giust, Davide; León, David; Ballesteros-Yañez, Inmaculada; Da Ros, Tatiana; Albasanz, José Luis; Martín, Mairena

2011-07-20

396

Comparative Transcriptome Analysis of Bacillus subtilis Responding to Dissolved Oxygen in Adenosine Fermentation  

PubMed Central

Dissolved oxygen (DO) is an important factor for adenosine fermentation. Our previous experiments have shown that low oxygen supply in the growth period was optimal for high adenosine yield. Herein, to better understand the link between oxygen supply and adenosine productivity in B. subtilis (ATCC21616), we sought to systematically explore the effect of DO on genetic regulation and metabolism through transcriptome analysis. The microarrays representing 4,106 genes were used to study temporal transcript profiles of B. subtilis fermentation in response to high oxygen supply (agitation 700 r/min) and low oxygen supply (agitation 450 r/min). The transcriptome data analysis revealed that low oxygen supply has three major effects on metabolism: enhance carbon metabolism (glucose metabolism, pyruvate metabolism and carbon overflow), inhibit degradation of nitrogen sources (glutamate family amino acids and xanthine) and purine synthesis. Inhibition of xanthine degradation was the reason that low oxygen supply enhanced adenosine production. These provide us with potential targets, which can be modified to achieve higher adenosine yield. Expression of genes involved in energy, cell type differentiation, protein synthesis was also influenced by oxygen supply. These results provided new insights into the relationship between oxygen supply and metabolism. PMID:21625606

Yin, Chun-Yun; Zhou, Ying; Ye, Bang-Ce

2011-01-01

397

The A2a adenosine receptor modulates the reinforcement efficacy and neurotoxicity of MDMA.  

PubMed

Adenosine is an endogenous purine nucleoside that plays a neuromodulatory role in the central nervous system. A2a adenosine receptors have been involved in reward-related processes, inflammatory phenomena and neurotoxicity reactions. In the present study, we investigated the role of A2a adenosine receptors on the acute pharmacological effects, reinforcement and neuroinflammation induced by MDMA administration. First, the acute effects of MDMA on body temperature, locomotor activity and anxiety-like responses were measured in A2a knockout mice and wild-type littermates. Second, MDMA reinforcing properties were evaluated using the intravenous self-administration paradigm. Finally, we assessed striatal astrogliosis and microgliosis as markers of MDMA neurotoxicity. Our results showed that acute MDMA produced a biphasic effect on body temperature and increased locomotor activity and anxiogenic-like responses in both genotypes. However, MDMA reinforcing properties were dramatically affected by the lack of A2a adenosine receptors. Thus, wild-type mice maintained MDMA self-administration under a fixed ratio 1 reinforcement schedule, whereas the operant response appeared completely abolished in A2a knockout mice. In addition, the MDMA neurotoxic regime produced an enhanced inflammatory response in striatum of wild-type mice, revealed by a significant increase in glial expression, whereas such activation was attenuated in mutant mice. This is the first report indicating that A2a adenosine receptors play a key role in reinforcement and neuroinflammation induced by the widely used psychostimulant. PMID:21262860

Ruiz-Medina, Jessica; Ledent, Catherine; Carretón, Olga; Valverde, Olga

2011-04-01

398

Adenosine uptake is the major effector of extracellular ATP toxicity in human cervical cancer cells.  

PubMed

In cervical cancer, HPV infection and disruption of mechanisms involving cell growth, differentiation, and apoptosis are strictly linked with tumor progression and invasion. Tumor microenvironment is ATP and adenosine rich, suggesting a role for purinergic signaling in cancer cell growth and death. Here we investigate the effect of extracellular ATP on human cervical cancer cells. We find that extracellular ATP itself has a small cytotoxic effect, whereas adenosine formed from ATP degradation by ectonucleotidases is the main factor responsible for apoptosis induction. The level of P2×7 receptor seemed to define the main cytotoxic mechanism triggered by ATP, since ATP itself eliminated a small subpopulation of cells that express high P2×7 levels, probably through its activation. Corroborating these data, blockage or knockdown of P2×7 only slightly reduced ATP cytotoxicity. On the other hand, cell viability was almost totally recovered with dipyridamole, an adenosine transporter inhibitor. Moreover, ATP-induced apoptosis and signaling-p53 increase, AMPK activation, and PARP cleavage-as well as autophagy induction were also inhibited by dipyridamole. In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells. PMID:25103241

Mello, Paola de Andrade; Filippi-Chiela, Eduardo Cremonese; Nascimento, Jéssica; Beckenkamp, Aline; Santana, Danielle Bertodo; Kipper, Franciele; Casali, Emerson André; Nejar Bruno, Alessandra; Paccez, Juliano Domiraci; Zerbini, Luiz Fernando; Wink, Marcia Rosângela; Lenz, Guido; Buffon, Andréia

2014-10-01

399

WS0701: a novel sedative-hypnotic agent acting on the adenosine system.  

PubMed

To characterize the sedative and hypnotic profile of the novel adenosine derivative ((3S,4R,5R)-3,4-dihydroxy-5-(6-((4-hydroxy-3-methoxybenzyl)amino)-9H-purin-9-yl)tetrahydrofuran-2-yl) methyl diaconate (WS0701), we performed a variety of behavioural tests and investigated the influence of WS0701 on various sleep stages. In mice, WS0701 significantly increased the number of entries and time spent in open arms in the elevated plus maze test, indicating an anxiolytic effect. WS0701 decreased locomotor activity counts and head dips in the hole-board test and enhanced sodium pentobarbital-induced hypnosis. However, WS0701 did not induce the loss of the righting reflex or amnesic effects in behavioural models. In rats, WS0701 exerted a sedative effect and markedly prolonged the time spent in non-rapid-eye-movement sleep, especially slow-wave sleep, but reduced the time spent in rapid-eye-movement sleep (REMS). Pretreatment with the selective adenosine A2a receptor antagonist SCH58261 attenuated the sedative and hypnotic effects of WS0701. WS0701 did not protect mice against picrotoxin-induced seizures, but inhibited adenosine deaminase activity and increased adenosine levels in the frontal cortex and hypothalamus of mice. In conclusion, WS0701 shows anxiolytic, sedative as well as sleep stage alterative effects, which may be related to the adenosine system. PMID:25171078

Bai, Xiao-Yu; Zhang, Xue-Qiong; Zhang, Yong-He; Wu, Song; Hao, Ling-Hua; Liu, Rui; Huang, Zhong-Lin; Zhang, Wei-Ku; Sun, Zong-Miao; Du, Guan-Hua

2014-10-01

400

Engineering human mesenchymal stem cells to release adenosine using miRNA technology.  

PubMed

Adenosine is an important modulator of metabolic activity with powerful tissue- and cell-protective functions. Adenosine kinase (ADK), the major adenosine-regulating enzyme, is critical to adapt its intra- and extra-cellular levels in response to environmental changes. Lentiviral RNAi-mediated down-regulation of ADK in human mesenchymal stem cells (hMSCs) has therefore been considered an effective tool for engineering therapeutically effective adenosine-releasing cell grafts that could constitute patient-identical autologous implants for clinical application. We constructed lentiviral vectors that coexpress miRNA directed against ADK and an emerald green fluorescent protein (EmGFP) reporter gene. Following lentiviral transduction of hMSCs, we demonstrated up to 80% down-regulation of ADK and 98% transduction efficiency. Transduced hMSCs continued to express EmGFP after 4-6 consecutive passages and EmGFP-positive hMSC grafts survived in the hippocampal fissure of mouse brains and provided efficient adenosine-dependent neuroprotection in a mouse model of seizure-induced cell loss. PMID:20686955

Ren, Gaoying; Boison, Detlev

2010-01-01

401

Neurochemical Measurement of Adenosine in Discrete Brain Regions of Five Strains of Inbred Mice  

PubMed Central

Adenosine (ADO), a non-classical neurotransmitter and neuromodulator, and its metabolites adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP), have been shown to play an important role in a number of biochemical processes. Although their signaling is well described, it has been difficult to directly, accurately and simultaneously quantitate these purines in tissue or fluids. Here, we describe a novel method for measuring adenosine (ADO) and its metabolites using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Using this chromatographic technique, we examined baseline levels of ADO and ATP, ADP and AMP in 6 different brain regions of the C57BL/6J mouse: stratum, cortex, hippocampus, olfactory bulb, substantia nigra and cerebellum and compared ADO levels in 5 different strains of mice (C57BL/6J, Swiss-Webster, FVB/NJ, 129P/J, and BALB/c). These studies demonstrate that baseline levels of purines vary significantly among the brain regions as well as between different mouse strains. These dissimilarities in purine concentrations may explain the variable phenotypes among background strains described in neurological disease models. PMID:24642754

Pani, Amar K.; Jiao, Yun; Sample, Kenneth J.; Smeyne, Richard J.

2014-01-01

402

Phosphorylation potential and adenosine release during norepinephrine infusion in guinea pig heart  

SciTech Connect

This study tested the hypothesis that adenosine released from isolated guinea pig hearts in response to norepinephrine is related to the cellular phosphorylation potential (PP;(ATP)/(ADP)(P{sub i})), where P{sub i} is inorganic phosphate. {sup 31}P-nuclear magnetic resonance (NMR) was used to measure the relative concentrations of P{sub i}, phosphocreatine (PCr), and ATP. After a control period, norepinephrine was infused for 20 min during which {sup 31}P-NMR spectra and samples of venous effluent were collected every minute. With norepinephrine infusion, PCr decreased rapidly to 72% of control by 8 min and then recovered to 80% of control for the remaining 12 min. ATP fell slowly to 70% of control over 20 min. P{sub i} increased to a peak at 2 min, then declined slowly to a steady state from 8 to 20 min. Adenosine release increased at 7 min and then slowly fell to a steady state from 10 to 20 min. There is hyperbolic relationship between adenosine release and PP; when the PP declines, a level is reached below which there is a rapid increase in adenosine release. These data support the hypothesis that adenosine release is regulated by the cellular PP as a closely related variable.

He, Miao-Xiang; Wangler, R.D.; Dillon, P.F.; Romig, G.D.; Sparks, H.V. (Michigan State Univ., East Lansing (USA))

1987-11-01

403

Rapid determination of adenosine deaminase kinetics using fast-scan cyclic voltammetry.  

PubMed

Adenosine deaminase is an enzyme involved in purine metabolism and its inhibitors are used as anticancer and antiviral drugs. In this study, we show that fast-scan cyclic voltammetry at carbon-fiber microelectrodes can be used to study the kinetics of adenosine deaminase by electrochemically monitoring decreases in adenosine concentration. Buffer and salt concentrations were shown to affect the enzyme kinetics and the inhibition by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and deoxycoformycin (DCF). In a Tris buffer containing salts that mimic cerebrospinal fluid, EHNA and DCF showed non-competitive inhibition with a K(i) of 1.7 +/- 0.6 nM and 1.2 +/- 0.2 nM, respectively. However, removing the divalent cations from the Tris buffer caused the inhibition to be competitive and reduced the K(i) for DCF by two orders of magnitude. In phosphate-buffered saline, the K(i) was 1.0 +/- 0.2 nM for EHNA and 3.6 +/- 0.3 pM for DCF, similar to literature values. Adenosine deaminase was also competitively inhibited by AgNO(3), showing it is susceptible to silver toxicity. Caffeine was found to increase adenosine deaminase activity. This is a fast, easy method for screening drug effects on enzyme kinetics and could be applied to other enzymatic reactions where there is a significant difference in the electroactivity of the reactant and product. PMID:20577678

Xu, Yida; Venton, B Jill

2010-09-14

404

Adenosine 5?-Triphosphate Flux Through the North Inlet Marsh System †  

PubMed Central

The distribution, fluctuation, and short-term transport of total microbial biomass (measured as adenosine 5?-triphosphate [ATP]) was investigated in a large salt marsh creek. Hourly samples were collected synoptically for 25 h from 10 boats positioned across the 320-m width of the creek. Samples were collected from three depths ranging from 0.2 to 8.0 m. Hourly data obtained from each station were graphed, plotting depth against ATP. Subsequently, interpolated ATP values were generated for every one-tenth depth from the surface to the bottom with the use of an 11-point proportional divider. A total of 2,750 values were generated, and a mean value of 0.865 mg of ATP per m3 was determined. Maximum levels of ATP were found at high tide and minimal values were found at low tide. The distribution of ATP concentrations was found to be complex, with no suggestion of vertical stratification; however, horizontal divisions were apparent. ATP values corrected for direction of flow or velocity indicated two ebb-directed channels; however, when considered in total, there was a net import of ATP through the interface. The total import of ATP for this 25-h sampling period was calculated to be 3.58 kg, corresponding to a net transport of 39.8 mg of ATP per s through the cross section. Results suggest that detailed characterization of a creek transect in terms of ATP or any similar parameter requires the simultaneous measurements of both the concentration of the parameter in question and the velocity at the time and point from which the sample was taken. PMID:16345382

Chrzanowski, Thomas H.; Stevenson, L. Harold; Kjerfve, Bjorn

1979-01-01

405

Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency  

PubMed Central

Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive, and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA), or hematopoietic stem cell gene therapy (HSC-GT). Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment. A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T- and B-cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties. PMID:22969765

Sauer, Aisha Vanessa; Brigida, Immacolata; Carriglio, Nicola; Aiuti, Alessandro

2012-01-01

406

The role of adenosine receptors in regulating production of tumour necrosis factor-? and chemokines by human lung macrophages  

PubMed Central

Background and purpose: Adenosine is a major endogenous regulator of macrophage function, and activates four specific adenosine receptors (A1, A2A, A2B and A3). Here, we have assessed in human lung macrophages the modulation of the expression of adenosine receptor mRNA by lipopolysaccharide (LPS), and the relative contributions of the different adenosine receptors to LPS-induced production of tumour necrosis factor (TNF)-? and chemokines. Experimental approach: Lung macrophages isolated from resected lungs were stimulated with LPS and treated with adenosine receptor agonists or/and antagonists. Adenosine receptor expression was assessed with qRT-PCR. Cytokines were measured in lung macrophage supernatants with elisa. Key results: LPS increased (about 400-fold) mRNA for A2A adenosine receptors, decreased mRNA for A1 and A2B, but had no effect on A3 adenosine receptor mRNA. The adenosine receptor agonist NECA inhibited TNF-? production concentration dependently, whereas the A1 receptor agonist, CCPA, and the A3 receptor agonist, AB-MECA, inhibited TNF-? production only at concentrations affecting A2A receptors. NECA also inhibited the production of CCL chemokines (CCL2, CCL3, CCL4, CCL5) and CXCL chemokines (CXCL9 and CXCL10), but not that of CXCL1, CXCL8 and CXCL5. Reversal of NECA-induced inhibition of TNF-? and chemokine production by the selective A2A adenosine receptor antagonist ZM 241385, but not the A2B receptor antagonist, MRS 1754, or the A3 receptor antagonist, MRS 1220, indicated involvement of A2A receptors. Conclusions and implications: LPS up-regulated A2A adenosine receptor gene transcription, and this receptor subtype mediated inhibition of the LPS-induced production of TNF-? and of a subset of chemokines in human lung macrophages. PMID:20136829

Buenestado, A; Delyle, S Grassin; Arnould, I; Besnard, F; Naline, E; Blouquit-Laye, S; Chapelier, A; Bellamy, JF; Devillier, P

2010-01-01

407

Circadian rhythm in adenosine A1 receptor of mouse cerebral cortex  

SciTech Connect

In order to investigate diurnal variation in adenosine A1 receptors binding parameters, Bmax and Kd values of specifically bound N6-cyclohexyl-({sup 3}H)adenosine were determined in the cerebral cortex of mice that had been housed under controlled light-dark cycles for 4 weeks. Significant differences were found for Bmax values measured at 3-hr intervals across a 24-h period, with low Bmax values during the light period and high Bmax values during the dark period. The amplitude between 03.00 and 18.00 hr was 33%. No substantial rhythm was found in the Kd values. It is suggested that the changes in the density of A1 receptors could reflect a physiologically-relevant mechanism by which adenosine exerts its modulatory role in the central nervous system.

Florio, C.; Rosati, A.M.; Traversa, U.; Vertua, R. (Univ. of Trieste (Italy))

1991-01-01

408

Autoradiographic localization of adenosine receptors in rat brain using (/sup 3/H)cyclohexyladenosine  

SciTech Connect

Adenosine (A1) receptor binding sites have been localized in rat brain by an in vitro light microscopic autoradiographic method. The binding of (/sup 3/H)N6-cyclohexyladenosine to slide-mounted rat brain tissue sections has the characteristics of A1 receptors. It is saturable with high affinity and has appropriate pharmacology and stereospecificity. The highest densities of adenosine receptors occur in the molecular layer of the cerebellum, the molecular and polymorphic layers of the hippocampus and dentate gyrus, the medial geniculate body, certain thalamic nuclei, and the lateral septum. High densities also are observed in certain layers of the cerebral cortex, the piriform cortex, the caudate-putamen, the nucleus accumbens, and the granule cell layer of the cerebellum. Most white matter areas, as well as certain gray matter areas, such as the hypothalamus, have negligible receptor concentrations. These localizations suggest possible central nervous system sites of action of adenosine.

Goodman, R.R.; Synder, S.H.

1982-09-01

409

Autoradiographic localization of adenosine uptake sites in rat brain using (/sup 3/H)nitrobenzylthioinosine  

SciTech Connect

The adenosine uptake site has been localized in rat brain by an in vitro light microscopic autoradiographic method, using (/sup 3/H)nitrobenzylthioinosine ((/sup 3/H)NBI) as the probe. The binding characteristics of (/sup 3/H)NBI on slide-mounted sections are comparable to those seen in studies performed on brain homogenates. A very high density of uptake sites occurs in the nucleus tractus solitarius, in the superficial layer of the superior colliculus, in several thalamic nuclei, and also in geniculate body nuclei. A high density of sites are also observed in the nucleus accumbens, the caudate putamen, the dorsal tegmentum area, the substantia nigra, and the central gray. The localization of the adenosine uptake site in brain may provide information on the functional activity of the site and suggests the involvement of the adenosine system in the central regulation of cardiovascular function.

Bisserbe, J.C.; Patel, J.; Marangos, P.J.

1985-02-01

410

Effects of triphenylsulphonium ions on mitochondria. Inhibition of adenosine triphosphatase activity.  

PubMed Central

Triphenylsulphonium ions inhibit mitochondrial oxidative phosphorylation and adenosine triphosphatase activity. The site of action is on the soluble F1 adenosine triphosphatase component. Triphenylsylphonium ions also inhibit electron transfer in the NAD-cytochrome b region of the respiratory chain. In both types of inhibition, triphenylsulphonium ions are effective at low concentrations, half-maximal inhibition being produced by a concentration of about 20-30 muM. These effects resemble the effects of alkylguanidines on mitochondria and are discussed in relation to the effects of alkylguanidines and other lipophilic cations such as ethidium and dibenzyldimethylammonium ions. A modification of the purification procedure for the soluble mitochondrial adenosine triphosphatase [Beechey, Hubbard, Linnett, Mitchell & Munn (1975) Biochem. J. 148, 533-537] IS DESCRIBED, WHICH YIELDS A PREPARATION WITH A HIGHER SPECIFIC ACTIVITY AND SHOWING FEWER BANDS IN GEL ELECTROPHORESIS. PMID:133679

Barrett, R H; Selwyn, M J

1976-01-01

411

Human ?-Defensin 2 Induces Extracellular Accumulation of Adenosine in Escherichia coli  

PubMed Central

Human ?-defensins are host defense peptides performing antimicrobial as well as immunomodulatory functions. The present study investigated whether treatment of Escherichia coli with human ?-defensin 2 could generate extracellular molecules of relevance for immune regulation. Mass spectrometry analysis of bacterial supernatants detected the accumulation of purine nucleosides triggered by ?-defensin 2 treatment. Other cationic antimicrobial peptides tested presented variable outcomes with regard to extracellular adenosine accumulation; human ?-defensin 2 was the most efficient at inducing this response. Structural and biochemical evidence indicated that a mechanism other than plain lysis was involved in the observed phenomenon. By use of isotope (13C) labeling, extracellular adenosine was found to be derived from preexistent RNA, and a direct interaction between the peptide and bacterial nucleic acid was documented for the first time for ?-defensin 2. Taken together, the data suggest that defensin activity on a bacterial target may alter local levels of adenosine, a well-known immunomodulator influencing inflammatory processes. PMID:23817371

Rohde, Manfred; Gutierrez, Maximiliano Gabriel; Molinari, Gabriella; Abraham, Wolf-Rainer

2013-01-01

412

Conversion of viramidine to ribavirin in vivo by adenosine deaminase and its inhibition by 2'-deoxycoformycin.  

PubMed

Previously we reported that viramidine is a prodrug of ribavirin and that adenosine deaminase catalyses viramidine deamination to ribavirin in vivo. This in vivo study explores this prodrug conversion in rats and inhibition by a potent adenosine deaminase inhibitor, 2'-deoxycoformycin. We found that conversion of viramidine to ribavirin was viramidine dose-dependent in rat plasma. A single intravenous dose of 0.25 mg/kg 2'-deoxycoformycin suppressed orally administered viramidine conversion to ribavirin in plasma by 50%. The inhibition was 2'-deoxycoformycin dose-dependent and a single dose of 2 mg/kg decreased the ribavirin/viramidine area under the concentration-time curve between 0 h and 6 h ratio by 2.5-fold. These findings provide strong evidence that adenosine deaminase plays a major role in converting viramidine to ribavirin in vivo. PMID:16542004

Wu, Jim Zhen; Yeh, Li-Tain; Lin, Chin-Chung; Hong, Zhi

2006-01-01

413

Role of adenosine in the antiepileptic effects of deep brain stimulation  

PubMed Central

Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine. PMID:25324724

Miranda, Maisa F.; Hamani, Clement; de Almeida, Antonio-Carlos G.; Amorim, Beatriz O.; Macedo, Carlos E.; Fernandes, Maria Jose S.; Nobrega, Jose N.; Aarao, Mayra C.; Madureira, Ana Paula; Rodrigues, Antonio M.; Andersen, Monica L.; Tufik, Sergio; Mello, Luiz E.; Covolan, Luciene

2014-01-01

414

Computational Elucidation of Structural Basis for Ligand Binding with Leishmania donovani Adenosine Kinase  

PubMed Central

Enzyme adenosine kinase is responsible for phosphorylation of adenosine to AMP and is crucial for parasites which are purine auxotrophs. The present study describes development of robust homology model of Leishmania donovani adenosine kinase to forecast interaction phenomenon with inhibitory molecules using structure-based drug designing strategy. Docking calculation using reported organic small molecules and natural products revealed key active site residues such as Arg131 and Asp16 for ligand binding, which is consistent with previous studies. Molecular dynamics simulation of ligand protein complex revealed the importance of hydrogen bonding with active site residues and solvent molecules, which may be crucial for successful development of drug candidates. Precise role of Phe168 residue in the active site was elucidated in this report that provided stability to ligand-protein complex via aromatic-? contacts. Overall, the present study is believed to provide valuable information to design a new compound with improved activity for antileishmanial therapeutics development. PMID:23984386

Kar, Rajiv K.; Ansari, Md. Yousuf; Suryadevara, Priyanka; Sahoo, Bikash R.; Sahoo, Ganesh C.; Dikhit, Manas R.; Das, Pradeep

2013-01-01

415

Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes  

PubMed Central

Aim: The present study investigated the effect of adenosine on Na+-K+ pumps in acutely isolated guinea pig (Cavia sp.) ventricular myocytes. Methods: The whole-cell, patch-clamp technique was used to record the Na+-K+ pump current (Ip) in acutely isolated guinea pig ventricular myocytes. Results: Adenosine inhibited the high DHO-affinity pump current (Ih) in a concentration-dependent manner, which was blocked by the selective adenosine A1 receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists staurosporine, GF 109203X or the specific ? isoform antagonist rottlerin. In addition, the inhibitory action of adenosine was mimicked by a selective A1 receptor agonist CCPA and a specific activator peptide of PKC-?, PP114. In contrast, the selective A2A receptor agonist CGS21680 and A3 receptor agonist Cl-IB-MECA did not affect Ih. Application of the selective A2A receptor antagonist SCH58261 and A3 receptor antagonist MRS1191 also failed to block the effect of adenosine. Furthermore, H89, a selective protein kinase A (PKA) antagonist, did not exert any effect on adenosine-induced Ih inhibition. Conclusion: The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of Ih via adenosine A1 receptors and the PKC-? isoform. PMID:19305421

Zhang, Zhe; Guo, Hui-cai; Zhang, Li-nan; Wang, Yong-li

2009-01-01

416

Adenosine A 2A receptor blockade prevents memory dysfunction caused by ?-amyloid peptides but not by scopolamine or MK-801  

Microsoft Academic Search

Adenosine A2A receptor antagonists alleviate memory deficits caused by aging or by administration of ?-amyloid peptides in rodents, which is in accordance with the beneficial effects of caffeine consumption (an adenosine receptor antagonist) on memory performance in aged individuals and in preventing Alzheimer's disease. We now tested if A2A receptor blockade affords a general beneficial effect in different experimental paradigms

Geanne M. A. Cunha; Paula M. Canas; Carolina S. Melo; Jörg Hockemeyer; Christa E. Müller; Catarina R. Oliveira; Rodrigo A. Cunha

2008-01-01

417

Role of adenosine in the ethanol-induced potentiation of the effects of general anesthetics in rats  

Microsoft Academic Search

Acetate, derived from ethanol metabolism in the liver, is released into the circulation and utilized in many tissues including the brain. The subsequent metabolism of acetate results in the production of adenosine that has a number of effects in the central nervous system. The purpose of the present studies, therefore, was to investigate the contribution of metabolically generated adenosine to

Paolo Campisi; F. J. Lou Carmichael; Mark Crawford; Hector Orrego; Jatinder M Khanna

1997-01-01

418

75 FR 8981 - Prospective Grant of Exclusive License: Treatment of Glaucoma by Administration of Adenosine A3...  

Federal Register 2010, 2011, 2012, 2013

...Grant of Exclusive License: Treatment of Glaucoma by Administration of Adenosine A3 Antagonists...adenosine A3 antagonists for treatment of glaucoma and intraocular pressure. DATES: Only...pressure, which is a means of treating glaucoma. The invention relates to several...

2010-02-26

419

Cloning and expression of an A1 adenosine receptor from rat brain  

SciTech Connect

The authors have used the polymerase chain reaction technique to selectively amplify guanine nucleotide-binding regulatory protein (G protein)-coupled receptor cDNA sequences from rat striatal mRNA, using sets of highly degenerate primers derived from transmembrane sequences of previously cloned G protein-coupled receptors. A novel cDNA fragment was identified, which exhibits considerable homology to various members of the G protein-coupled receptor family. This fragment was used to isolate a full-length cDNA from a rat striatal library. A 2.2-kilobase clone was obtained that encodes a protein of 326 amino acids with seven transmembrane domains, as predicted by hydropathy analysis. Stably transfected mouse A9-L cells and Chinese hamster ovary cells that expressed mRNA for this clone were screened with putative receptor ligands. Saturable and specific binding sites for the A1 adenosine antagonist (3H)-1,3-dipropyl-8-cyclopentylxanthine were identified on membranes from transfected cells. The rank order of potency and affinities of various adenosine agonist and antagonist ligands confirmed the identity of this cDNA clone as an A1 adenosine receptor. The high affinity binding of A1 adenosine agonists was shown to be sensitive to the nonhydrolyzable GTP analog guanylyl-5{prime}-imidodiphosphate. In adenylyl cyclase assays, adenosine agonists inhibited forskolin-stimulated cAMP production by greater than 50%, in a pharmacologically specific fashion. Northern blot and in situ hybridization analyses of receptor mRNA in brain tissues revealed two transcripts of 5.6 and 3.1 kilobases, both of which were abundant in cortex, cerebellum, hippocampus, and thalamus, with lower levels in olfactory bulb, striatum, mesencephalon, and retina. These regional distribution data are in good agreement with previous receptor autoradiographic studies involving the A1 adenosine receptor.

Mahan, L.C.; McVittie, L.D.; Smyk-Randall, E.M.; Nakata, H.; Monsma, F.J. Jr.; Gerfen, C.R.; Sibley, D.R. (Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD (USA))

1991-07-01

420

Extracellular generation of adenosine by the ectonucleotidases CD39 and CD73 promotes dermal fibrosis.  

PubMed

Adenosine has an important role in inflammation and tissue remodeling and promotes dermal fibrosis by adenosine receptor (A2AR) activation. Adenosine may be formed intracellularly from adenine nucleotides or extracellularly through sequential phosphohydrolysis of released ATP by nucleoside triphosphate diphosphohydrolase (CD39) and ecto-5'-nucleotidase (CD73). Because the role of these ecto-enzymes in fibrosis appears to be tissue specific, we determined whether these ectonucleotidases were directly involved in diffuse dermal fibrosis. Wild-type and mice globally deficient in CD39 knockout (CD39KO), CD73 (CD73KO), or both (CD39/CD73DKO) were challenged with bleomycin. Extracellular adenosine levels and dermal fibrosis were quantitated. Adenosine release from skin cultured ex vivo was increased in wild-type mice after bleomycin treatment but remained low in skin from CD39KO, CD73KO, or CD39/CD73DKO bleomycin-treated mice. Deletion of CD39 and/or CD73 decreased the collagen content, and prevented skin thickening and tensile strength increase after bleomycin challenge. Decreased dermal fibrotic features were associated with reduced expression of the profibrotic mediators, transforming growth factor-?1 and connective tissue growth factor, and diminished myofibroblast population in CD39- and/or CD73-deficient mice. Our work supports the hypothesis that extracellular adenosine, generated in tandem by ecto-enzymes CD39 and CD73, promotes dermal fibrogenesis. We suggest that biochemical or biological inhibitors of CD39 and/or CD73 may hold promise in the treatment of dermal fibrosis in diseases such as scleroderma. PMID:24266925

Fernández, Patricia; Perez-Aso, Miguel; Smith, Gideon; Wilder, Tuere; Trzaska, Sean; Chiriboga, Luis; Franks, Andrew; Robson, Simon C; Cronstein, Bruce N; Chan, Edwin S L

2013-12-01

421

Regulation of photoreceptor gap junction phosphorylation by adenosine in zebrafish retina  

PubMed Central

Electrical coupling of photoreceptors through gap junctions suppresses voltage noise, routes rod signals into cone pathways, expands the dynamic range of rod photoreceptors in high scotopic and mesopic illumination, and improves detection of contrast and small stimuli. In essentially all vertebrates, connexin 35/36 (gene homologues Cx36 in mammals, Cx35 in other vertebrates) is the major gap junction protein observed in photoreceptors, mediating rod-cone, cone-cone, and possibly rod-rod communication. Photoreceptor coupling is dynamically controlled by the day/night cycle and light/dark adaptation, and is directly correlated with phosphorylation of Cx35/36 at two sites, serine110 and serine 276/293 (homologous sites in teleost fish and mammals respectively). Activity of protein kinase A (PKA) plays a key role during this process. Previous studies have shown that activation of dopamine D4 receptors on photoreceptors inhibits adenylyl cyclase, down-regulates cAMP and PKA activity, and leads to photoreceptor uncoupling, imposing the daytime/light condition. In this study we explored the role of adenosine, a nighttime signal with a high extracellular concentration at night and a low concentration in the day, in regulating photoreceptor coupling by examining photoreceptor Cx35 phosphorylation in zebrafish retina. Adenosine enhanced photoreceptor Cx35 phosphorylation in daytime, but with a complex dose-response curve. Selective pharmacological manipulations revealed that adenosine A2a receptors provide a potent positive drive to phosphorylate photoreceptor Cx35 under the influence of endogenous adenosine at night. A2a receptors can be activated in the daytime as well by micromolar exogenous adenosine. However, the higher affinity adenosine A1 receptors are also present and have an antagonistic though less potent effect. Thus the nighttime/darkness signal adenosine provides a net positive drive on Cx35 phosphorylation at night, working in opposition to dopamine to regulate photoreceptor coupling via a push-pull mechanism. However, the lower concentration of adenosine present in the daytime actually reinforces the dopamine signal through action on the A1 receptor. PMID:24844306

Li, Hongyan; Chuang, Alice Z.; O'Brien, John

2014-01-01

422

Neuroprotection by caffeine and adenosine A 2A receptor blockade of ? -amyloid neurotoxicity  

Microsoft Academic Search

Adenosine is a neuromodulator in the nervous system and it has recently been observed that pharmacological blockade or gene disruption of adenosine A2A receptors confers neuroprotection under different neurotoxic situations in the brain. We now observed that coapplication of either caffeine (1 - 25mm) or the selective A2A receptor antagonist, 4-(2-(7-amino-2(2-furyl)(1,2,4)triazolo (2,3-a)(1,3,5)triazin-5-ylamino)ethyl)phenol (ZM 241385, 50 nm), but not the A

Oscar P Dall'lgna; Lisiane O. Porciuncula; Diogo O. Souza; Rodrigo A. Cunha; Diogo R. Lara

2003-01-01

423

Glomeruli and microvessels of the rabbit kidney contain both A 1 - and A 2 -adenosine receptors  

Microsoft Academic Search

Rabbit renal cortices were fractionated by collagenase dispersion and glomeruli, microvessels and tubuli purified on a discontinuous sucrose gradient. Binding experiments with (-)[125I]N6-(4-hydroxyphenylisopropyl)-adenosine ([125I]HPIA) provided evidence for the presence of A1-adeno