Involvement of adenosine deaminase and adenosine kinase in regulating extracellular adenosine concentration in rat hippocampal slices

1995 ◽  
Vol 26 (4) ◽  
pp. 387-395 ◽  
Author(s):  
H Lloyd
Keyword(s):  
Adenosine Deaminase ◽  
Hippocampal Slices ◽  
Adenosine Kinase ◽  
Extracellular Adenosine ◽  
Adenosine Concentration

Renal interstitial adenosine metabolism during ischemia in dogs

2001 ◽  
Vol 280 (2) ◽  
pp. F231-F238 ◽  
Author(s):  
Akira Nishiyama ◽  
Shoji Kimura ◽  
Hong He ◽  
Katsuyuki Miura ◽  
Matlubur Rahman ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Adenosine Kinase ◽  
The Other ◽  
Local Inhibition ◽  
Other Hand ◽  
Adenosine Concentration ◽  
Anesthetized Dogs ◽  
Fluorometric Analysis

The present study was conducted to determine the metabolism of renal interstitial adenosine under resting conditions and during ischemia. By using a microdialysis method with HPLC-fluorometric analysis, renal interstitial concentrations of adenosine, inosine, and hypoxanthine were assessed in pentobarbital-anesthetized dogs. Average basal renal interstitial concentrations of adenosine, inosine, and hypoxanthine were 0.18 ± 0.04, 0.31 ± 0.05, and 0.35 ± 0.05 μmol/l, respectively. Local inhibition of adenosine kinase with iodotubercidin (10 μmol/l in perfusate) or inhibition of adenosine deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 100 μmol/l in perfusate) did not change adenosine concentrations in the nonischemic kidneys (0.18 ± 0.04 and 0.24 ± 0.05 μmol/l, respectively). On the other hand, treatment with iodotubercidin+EHNA significantly increased adenosine concentration (0.52 ± 0.07 μmol/l) with significant decreases in inosine and hypoxanthine levels (0.13 ± 0.03 and 0.19 ± 0.04 μmol/l, respectively). During 30 min of ischemia, adenosine, inosine, and hypoxanthine were significantly increased to 0.76 ± 0.29, 2.14 ± 0.45, and 21.8 ± 4.7 μmol/l, respectively. The treatment with iodotubercidin did not alter ischemia-induced increase in adenosine (0.84 ± 0.18 μmol/l); however, EHNA alone markedly enhanced adenosine accumulation (13.54 ± 2.16 μmol/l), the value of which was not augmented by an addition of iodotubercidin (15.80 ± 1.24 μmol/l). In contrast, ischemia-induced increases in inosine and hypoxanthine were inversely diminished by the treatment with iodotubercidin+EHNA (0.90 ± 0.20 and 9.86 ± 1.96 μmol/l, respectively). These results suggest that both adenosine kinase and adenosine deaminase contribute to the metabolism of renal interstitial adenosine under resting conditions, whereas adenosine produced during ischemia is mainly metabolized by adenosine deaminase and the rephosphorylation of adenosine by adenosine kinase is small.

scholarly journals 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

1978 ◽  
Vol 174 (3) ◽  
pp. 965-977 ◽  
Author(s):  
J R S Arch ◽  
E A Newsholme
Keyword(s):  
Adenosine Deaminase ◽  
Physiological Role ◽  
Adenosine Kinase ◽  
British Library ◽  
Adenosine Concentration ◽  
Effects Of Ph ◽  
The Difference ◽  
Low Activity

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.

scholarly journals Intracellular Acidification Causes Adenosine Release During States of Hyperexcitability in the Hippocampus

2009 ◽  
Vol 102 (3) ◽  
pp. 1984-1993 ◽  
Author(s):  
Chris G. Dulla ◽  
Bruno G. Frenguelli ◽  
Kevin J. Staley ◽  
Susan A. Masino
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Ph ◽  
Hippocampal Slice ◽  
Dominant Role ◽  
Hippocampal Slices ◽  
Extracellular Ph ◽  
Ph Change ◽  
Extracellular Adenosine ◽  
Adenosine Concentration

Decreased pH increases extracellular adenosine in CNS regions as diverse as hippocampus and ventral medulla. However, thus far there is no clear consensus whether the critical pH change is a decrease in intracellular and/or extracellular pH. Previously we showed that a decrease in extracellular pH is necessary and a decrease in intracellular pH alone is not sufficient, to increase extracellular adenosine in an acute hippocampal slice preparation. Here we explored further the role of intracellular pH under different synaptic conditions in the hippocampal slice. When synaptic excitability was increased, either during γ-aminobutyric acid type A receptor blockade in CA1 or after the induction of persistent bursting in CA3, a decrease in intracellular pH alone was now sufficient to: 1) elevate extracellular adenosine concentration, 2) activate adenosine A1 receptors, 3) decrease excitatory synaptic transmission (CA1), and 4) attenuate burst frequency in an in vitro seizure model (CA3). Hippocampal slices obtained from adenosine A1 receptor knockout mice did not exhibit these pH-mediated effects on synaptic transmission, further confirming the role of adenosine acting at the adenosine A1 receptor. Taken together, these data strengthen and add significantly to the evidence outlining a change in pH as an important stimulus influencing extracellular adenosine. In addition, we identify conditions under which intracellular pH plays a dominant role in regulating extracellular adenosine concentrations.

scholarly journals Adenosine turnover in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Detlev Boison
Keyword(s):  
Cell Surface ◽  
Adenosine Deaminase ◽  
Inorganic Phosphate ◽  
G Protein Coupled Receptors ◽  
Adenosine Kinase ◽  
Nucleoside Transporters ◽  
Nucleotidase Activity ◽  
Extracellular Adenosine ◽  
Adenosylhomocysteine Hydrolase ◽  
G Protein Coupled

A multifunctional, ubiquitous molecule, adenosine acts at cell-surface G protein-coupled receptors, as well as numerous enzymes, including protein kinases and adenylyl cyclase. Extracellular adenosine is thought to be produced either by export or by metabolism, predominantly through ecto-5’-nucleotidase activity (also producing inorganic phosphate). It is inactivated either by extracellular metabolism via adenosine deaminase (also producing ammonia) or, following uptake by nucleoside transporters, via adenosine deaminase or adenosine kinase (requiring ATP as co-substrate). Intracellular adenosine may be produced by cytosolic 5’-nucleotidases or through S-adenosylhomocysteine hydrolase (also producing L-homocysteine).

scholarly journals Adenosine turnover (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Detlev Boison
Keyword(s):  
Cell Surface ◽  
Adenosine Deaminase ◽  
Inorganic Phosphate ◽  
G Protein Coupled Receptors ◽  
Adenosine Kinase ◽  
Nucleoside Transporters ◽  
Nucleotidase Activity ◽  
Extracellular Adenosine ◽  
Adenosylhomocysteine Hydrolase ◽  
G Protein Coupled

A multifunctional, ubiquitous molecule, adenosine acts at cell-surface G protein-coupled receptors, as well as numerous enzymes, including protein kinases and adenylyl cyclase. Extracellular adenosine is thought to be produced either by export or by metabolism, predominantly through ecto-5’-nucleotidase activity (also producing inorganic phosphate). It is inactivated either by extracellular metabolism via adenosine deaminase (also producing ammonia) or, following uptake by nucleoside transporters, via adenosine deaminase or adenosine kinase (requiring ATP as co-substrate). Intracellular adenosine may be produced by cytosolic 5’-nucleotidases or through S-adenosylhomocysteine hydrolase (also producing L-homocysteine).

scholarly journals L-Arginine Intake Effect on Adenine Nucleotide Metabolism in Rat Parenchymal and Reproductive Tissues

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
G. Kocic ◽  
J. Nikolic ◽  
T. Jevtovic-Stoimenov ◽  
D. Sokolovic ◽  
H. Kocic ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Tissue Growth ◽  
Nucleotide Metabolism ◽  
Amp Deaminase ◽  
Male Impotence ◽  
Adenine Nucleotide Metabolism ◽  
Adenosine Concentration ◽  
Male Wistar Rats

L-arginine is conditionally essetcial amino acid, required for normal cell growth, protein synthesis, ammonia detoxification, tissue growth and general performance, proposed in the treatment of men sterility and prevention of male impotence. The aim of the present paper was to estimate the activity of the enzymes of adenine nucleotide metabolism:5′-nucleotidase (5′-NU), adenosine deaminase (ADA), AMP deaminase, and xanthine oxidase (XO), during dietary intake of L-arginine for a period of four weeks of male Wistar rats. Adenosine concentration in tissues is maintained by the relative activities of the adenosine-producing enzyme,5′-NU and the adenosine-degrading enzyme-ADA adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide metabolism in liver, kidney, and testis tissue toward the activation of adenosine production, by increased5′-NU activity and decreased ADA activity. Stimulation of adenosine accumulation could be of importance in mediating arginine antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects. Assuming that the XO activity reflects the rate of purine catabolism in the cell, while the activity of AMP deaminase is of importance in ATP regeneration, reduced activity of XO, together with the increased AMP-deaminase activity, may suggest that adenine nucleotides are presumably directed to the ATP regenerating process during dietary L-arginine intake.

The effect of diazepam on adenosine uptake and adenosine-stimuiated adenylate cyclase in guinea-pig brain

1982 ◽  
Vol 60 (3) ◽  
pp. 302-307 ◽  
Author(s):  
M. J. York ◽  
L. P. Davies
Keyword(s):  
Adenylate Cyclase ◽  
Guinea Pig ◽  
Adenosine Deaminase ◽  
Small Component ◽  
Extracellular Adenosine ◽  
Pig Brain ◽  
Adenosine Uptake ◽  
Adenosine Antagonist ◽  
Guinea Pig Brain ◽  
Stimulation Of

We have used the adenosine-stimulated adenylate cyclase of guinea-pig brain to examine the potency of diazepam as an adenosine uptake inhibitor. Diazepam at concentrations in the range 10–500 μM stimulates the production of cAMP in incubated slices of guinea-pig cerebral cortex, with maximal fivefold stimulations over basal levels by 200 μM diazepam. The increases can be largely (but not completely) blocked by the adenosine antagonist theophylline or by addition of excess adenosine deaminase to the system. It appears that the stimulation of cAMP production is due to a blockade of adenosine uptake which results in an increase in extracellular adenosine and concomitant activation of the adenosine receptor coupled to adenylate cyclase. Since the cAMP response to standard adenosine uptake blockers (dipyridamole, dilazep) can be completely blocked by theophylline or adenosine deaminase, a small component of the diazepam response cannot be explained by an adenosine effect. The concentration of diazepam at which the first significant cAMP increase occurs is 10 μM or slightly lower. This is significantly higher than the concentration of diazepam needed to saturate the pharmacologically characterized central nervous system receptors for benzodiazepines.

Survival of energy failure in the anoxic frog brain: delayed release of glutamate.

1997 ◽  
Vol 200 (22) ◽  
pp. 2913-2917 ◽  
Author(s):  
P L Lutz ◽  
R Reiners
Keyword(s):  
Neurotransmitter Release ◽  
Energy Charge ◽  
Atp Depletion ◽  
Extracellular Adenosine ◽  
Frog Brain ◽  
Adenosine Concentration ◽  
Excitatory Neurotransmitters ◽  
The Relationship ◽  
Brain Energy ◽  
Energy Failure

This study investigated the relationship between energy failure and neurotransmitter release in the frog (Rana pipiens) brain during 1-3 h of anoxia. Unlike truly anoxia-tolerant species, the frog does not defend its brain energy charge. When exposed to anoxia at 25 degrees C, there is an immediate fall in brain ATP levels, which reach approximately 20% of normoxic levels in approximately 60 min. The frog, nevertheless, survives another 1-2 h of anoxia. At 100 min of anoxia, there is an increase in extracellular adenosine concentration, probably originating from the increased intracellular adenosine concentration caused by the breakdown of intracellular ATP. Increases in the levels of extracellular glutamate and GABA do not occur until 1-2 h after ATP depletion. This response is quite unlike that recorded for other vertebrates, anoxia-tolerant or anoxia-intolerant, where energy failure quickly results in an uncontrolled and neurotoxic release of excitatory neurotransmitters. In the frog, the delay in excitotoxic neurotransmitter release may be one of the factors that allow a period of survival after energy failure. Clearly, energy failure by itself is not a fatal event in the frog brain.

Role of adenosine in postprandial and reactive hyperemia in canine jejunum

1992 ◽  
Vol 263 (4) ◽  
pp. G487-G493 ◽  
Author(s):  
D. R. Sawmiller ◽  
C. C. Chou
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Adenosine Deaminase ◽  
Reactive Hyperemia ◽  
Concentration Difference ◽  
Adenosine Concentration ◽  
Anesthetized Dogs ◽  
Series Of Experiments ◽  
Increased Blood Flow

The role of adenosine in postprandial jejunal hyperemia was investigated by determining the effect of placement of predigested food into the jejunal lumen on blood flow and oxygen consumption before and during intra-arterial infusion of dipyridamole (1.5 microM arterial concn) or adenosine deaminase (9 U/ml arterial concn) in anesthetized dogs. Neither drug significantly altered resting jejunal blood flow and oxygen consumption. Before dipyridamole or deaminase, food placement increased blood flow by 30-36%, 26-42%, and 21-46%, and oxygen consumption by 13-22%, 21-22%, and 26-29%, during 0- to 3-, 4- to 7-, and 8- to 11-min placement periods, respectively. Adenosine deaminase abolished the entire 11-min hyperemia, whereas dipyridamole significantly enhanced the initial 7-min hyperemia (45-49%). Both drugs abolished the initial 7-min food-induced increase in oxygen consumption. Dipyridamole attenuated (14%), whereas deaminase did not alter (28%), the increased oxygen consumption that occurred at 8-11 min. Adenosine deaminase also prevented the food-induced increase in venoarterial adenosine concentration difference. In separate series of experiments, luminal placement of food significantly increased jejunal lymphatic adenosine concentration and release. Also, reactive hyperemia was accompanied by an increase in venous adenosine concentration and release. This study provides further evidence to support the thesis that adenosine plays a role in postprandial and reactive hyperemia in the canine jejunum.

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