Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetylcholine and ATP are costored and coreleased during synaptic activity at the electric organ of Torpedo. It has been suggested that released ATP is converted to adenosine at the synaptic cleft, and in turn this nucleoside would depress the evoked release of acetylcholine. In the present communication we have used a chemiluminescent reaction that let us to monitor continuously the presence of adenosine in this preparation. The chemiluminescent reaction is based on the conversion of adenosine into uric acid and H2O2 by adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase enzymes. The hydrogen peroxide has been detected by peroxidase-luminol mixture. The reaction has a sensitivity on the picomol range and discerned between Adenosine, AMP, ADP, and ATP. We have developed this technique in the hope of understanding whether adenosine is released during synaptic activity or it comes from the released ATP. We have studied the release or formation of adenosine in fragments of the electric organ and in isolated cholinergic nerve terminals obtained from it. In both conditions we have followed the effect of potassium stimulation upon the detection of adenosine. Potassium stimulation increased the extracellular adenosine either in slices or the synaptosomal fraction of Torpedo electric organ. The presence of alpha, beta-methylene ADP, an inhibitor of 5'-nucleotidase, inhibits the detection of adenosine, suggesting that extracellular adenosine is a consequence of ectocellular dephosphorylation of released ATP.
 ...
PMID:The release of adenosine at the electric organ of Torpedo. A study using a continuous chemiluminescent method. 232 27

1-Methylisoguanosine, a marine natural product analogue of adenosine, with moderate activity as a benzodiazepine receptor ligand, has previously been shown to have muscle-relaxant and hypothermic activity in mice in vivo. The present experiments showed that the benzodiazepine antagonist Ro15-1788 did not block the in vivo muscle-relaxant and hypothermic effects of 1-methylisoguanosine, suggesting that these particular actions are not due to interactions with benzodiazepine receptors. When applied by microiontophoresis near spontaneously-active neurones or neurones activated by ACh, DL-homocysteate or glutamate in the ventrobasal thalamus of anaesthetized rats, 1-methylisoguanosine had a depressant action; it was similar to adenosine in potency and in its ability to be antagonized by 8-(parasulphophenyl)theophylline. The depression was usually longer lasting than that caused by adenosine, consistent with previous neurochemical data showing it to be resistant to adenosine deaminase and a poor substrate for the uptake system for adenosine in the CNS. These results suggest that the major pharmacological/behavioural actions of 1-methylisoguanosine in vivo are more likely to be caused by an interaction with adenosine receptors, rather than with benzodiazepine sites.
 ...
PMID:1-Methylisoguanosine: interaction with central adenosine receptors and lack of antagonism of its in vivo effects by a benzodiazepine antagonist. 303 18

A factor (Substance B) has been isolated from brain which reverses the presynaptically-modulated inhibition of evoked ACh release from both guinea-pig myenteric plexus-longitudinal muscle synaptosomes and the intact strip. Inhibitory modulating agents whose activity is reversed by Substance B include oxotremorine, 2-chloroadenosine, clonidine, and morphine. In addition to brain, Substance B is also present in heart and ileum but not in liver or kidney. As determined by Biogel P2 chromatography, this factor appears to have a molecular weight of around 700. It is not destroyed by preincubation with periodate, amylase, adenosine deaminase, pronase, trypsin, phospholipase C or carboxypeptidase Y.
 ...
PMID:Isolation of a factor that reverses presynaptic inhibition of acetylcholine release. 357 23

The inhibitory effects of adenosine, ATP, 5'-adenylyl methylene diphosphonate (beta, gamma-meATP) and adenosine 5'-alpha, beta-methylene triphosphonate (alpha, beta-meATP) were compared on the cholinergic twitch responses to transmural stimulation of the guinea-pig ileum. Adenosine, ATP and beta, gamma-meATP reduced the twitch responses in a concentration dependent manner. Theophylline antagonized and dipyridamole potentiated the inhibitory responses to adenosine, ATP and beta, gamma-meATP. Inhibitory responses to alpha, beta-meATP were usually preceded by an enhancement in twitch height. Contractions of the unstimulated ileum to alpha, beta-meATP were blocked by atropine and tetrodotoxin while those elicited by ATP were unaffected, which suggests that the initial excitatory effects of alpha, beta-meATP may be due to its ability to release ACh from cholinergic nerve terminals. Use of high pressure liquid chromatography and bioluminescence assay techniques demonstrated the ability of the tissue to degrade ATP and beta, gamma-meATP and, at a much slower rate, alpha, beta-meATP. Inhibitory responses to ATP, AMP and beta, gamma-meATP were reduced by adenosine deaminase, which also abolished responses to adenosine. 5'-AMP deaminase abolished responses to AMP and adenosine, and reduced those to ATP and beta, gamma-meATP. The results suggest that the inhibitory effect of ATP on cholinergic neurotransmission is due to its rapid breakdown to AMP or adenosine, which act on prejunctional P1-purinoceptors.
 ...
PMID:Evidence for the presence of P1-purinoceptors on cholinergic nerve terminals in the guinea-pig ileum. 627 50

Acetylcholine acting via muscarinic cholinoceptors decreased phosphorylation of phospholamban and troponin I without reducing adenosine 3',5'-cyclic monophosphate (cAMP) levels or cAMP-dependent protein kinase activity ratio in the presence of 10-100 nM isoproterenol in guinea pig ventricular myocytes. The effect of acetylcholine was more pronounced when adenosine deaminase (5 U/ml) was present and incubation period was short (10 s). Okadaic acid, an inhibitor of protein phosphatase activity, blocked the acetylcholine-mediated inhibition of isoproterenol-stimulated phosphorylation of phospholamban. It is suggested that acetylcholine reduces protein phosphorylation by a cAMP-independent mechanism in guinea pig ventricular myocytes.
 ...
PMID:M2-specific muscarinic cholinergic receptor-mediated inhibition of cardiac regulatory protein phosphorylation. 816 Aug 16

The modulation by adenosine analogues and endogenous adenosine of the electrically evoked release of [3H]acetylcholine ([3H]ACh) was compared in subslices of the three areas of the rat hippocampus (CA1, CA3, and dentate gyrus). The mixed A1/A2 agonist 2-chloroadenosine (CADO; 2-10 microM) inhibited, in a concentration-dependent manner, the release of [3H]ACh from the three hippocampal areas, being more potent in the CA1 and CA3 areas than in the dentate gyrus. The inhibitory effect of CADO (5 microM) on [3H]ACh release was prevented by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 50 nM) in the three hippocampal areas and was converted in an excitatory effect in the CA3 and dentate gyrus areas. The A2A agonist CGS-21680 (30 nM) produced a greater increase of the evoked release of [3H]ACh in the CA3 than in the dentate gyrus areas, whereas no consistent effect was found in the CA1 area or in the whole hippocampal slice. The excitatory effect of CGS-21680 (30 nM) in the CA3 area was prevented by the adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 microM). Both adenosine deaminase (2 U/ml) and DPCPX (250 nM) increased the evoked release of [3H]ACh in the CA1 and CA3 areas but not in the dentate gyrus. The amplitude of the effect of DPCPX and adenosine deaminase was similar in the CA1 area, but in the CA3 area DPCPX produced a greater effect than adenosine deaminase. It is concluded that the electrically evoked release of [3H]ACh in the three areas of the rat hippocampus can be differentially modulated by adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Excitatory and inhibitory effects of A1 and A2A adenosine receptor activation on the electrically evoked [3H]acetylcholine release from different areas of the rat hippocampus. 820 30

The effect of forskolin (FSK) on [3H]-acetylcholine release ([3H]-ACh) from the phrenic motor nerve terminals, and its modification by adenosine deaminase (ADA), by the A2-adenosine receptor agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamide adenosine (CGS 21680C), by the A1-adenosine receptor agonist R-N6-phenylisopropyl adenosine (R-PIA), by the A2-antagonist N-(2-(dimethylamino)-ethyl)-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3 -dipropyl-1H-purine-8-yl)-benzene sulphonamide (PD 115,199), and by the A1-antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) were studied on the rat phrenic-hemidiaphragm preparation. It is concluded that the excitatory effect of FSK on evoked [3H]-ACh release depends on tonic A2-adenosine receptor activation.
 ...
PMID:Facilitation of [3H]-ACh release by forskolin depends on A2-adenosine receptor activation. 846 31

1. In the present work, we investigated the action of adenosine originating from extracellular catabolism of adenine nucleotides, in two preparations where synaptic transmission is modulated by both inhibitory A1 and excitatory A(2a)-adenosine receptors, the rat hippocampal Schaffer fibres/CA1 pyramid synapses and the rat innervated hemidiaphragm. 2. Endogenous adenosine tonically inhibited synaptic transmission, since 0.5-2 u ml-1 of adenosine deaminase increased both the population spike amplitude (30 +/- 4%) and field excitatory post-synaptic potential (f.e.p.s.p.) slope (27 +/- 4%) recorded from hippocampal slices and the evoked [3H]-acetylcholine ([3H]-ACh) release from the motor nerve terminals (25 +/- 2%). 3. alpha, beta-Methylene adenosine diphosphate (AOPCP) in concentrations (100-200 microM) that almost completely inhibited the formation of adenosine from the extracellular catabolism of AMP, decreased population spike amplitude by 39 +/- 5% and f.e.p.s.p. slope by 32 +/- 3% in hippocampal slices and [3H]-ACh release from motor nerve terminals by 27 +/- 3%. 4. Addition of exogenous 5'-nucleotidase (5 u ml-1) prevented the inhibitory effect of AOPCP on population spike amplitude and f.e.p.s.p. slope by 43-57%, whereas the P2 antagonist, suramin (100 microM), did not modify the effect of AOPCP. 5. In both preparations, the effect of AOPCP resulted from prevention of adenosine formation since it was no longer evident when accumulation of extracellular adenosine was hindered by adenosine deaminase (0.5-2 u ml-1). The inhibitory effect of AOPCP was still evident when A1 receptors were blocked by 1,3-dipropyl-8-cyclopentylxanthine (2.5-5 nM), but was abolished by the A2 antagonist, 3,7-dimethyl-1-propargylxanthine (10 microM). 6. These results suggest that adenosine originating from catabolism of released adenine nucleotides preferentially activates excitatory A2 receptors in hippocampal CAI pyramid synapses and in phrenic motor nerve endings.
 ...
PMID:Preferential activation of excitatory adenosine receptors at rat hippocampal and neuromuscular synapses by adenosine formed from released adenine nucleotides. 888 6

We have investigated the effect of endogenous adenosine on the release of [3H]acetylcholine ([3H]ACh) in cultured chick amacrine-like neurons. The release of [3H]ACh evoked by 50 mM KCl was mostly Ca2+ dependent, and it was increased in the presence of adenosine deaminase and in the presence of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptor antagonist. The effect of adenosine on [3H]ACh release was sensitive to pertussis toxin (PTX) and was due to a selective inhibition of N-type Ca2+ channels. Ligand binding studies using [3H]DPCPX confirmed the presence of adenosine A1 receptors in the preparation. Using specific inhibitors of the plasma membrane adenosine carriers and of the ectonucleotidases, we found that the extracellular accumulation of adenosine in response to KCl depolarization was due to the release of endogenous adenosine per se and to the extracellular conversion of released nucleotides into adenosine. Activation of adenosine A1 receptors was without effect on the intracellular levels of cyclic AMP under depolarizing conditions, but it inhibited the accumulation of inositol phosphates. Our results indicate that in cultured amacrine-like neurons, the Ca2+-dependent release of [3H]ACh evoked by KCl is under tonic inhibition by adenosine, which activates A1 receptors. The effect of adenosine on the [3H]ACh release may be due to a direct inhibition of N-type Ca2+ channels and/or secondary to the inhibition of phospholipase C and involves the activation of PTX-sensitive G proteins.
 ...
PMID:Modulation of [3H]acetylcholine release from cultured amacrine-like neurons by adenosine A1 receptors. 972 33

We studied the effect of endogenous adenosine on the release of [3H]acetylcholine ([3H]ACh) in cultures enriched (96.4+/-0.4%) in rat cholinergic amacrine-like neurons, as determined by labeling with an antibody against choline acetyltransferase. A small population of these cells also contained GABA. Using these cultures we observed that both [3H]ACh release, which was largely Ca2+-dependent, and 45Ca2+ influx, evoked by depolarization with 50 mM KCl, were increased when adenosine A1 receptor activation was prevented by removal of endogenous adenosine with adenosine deaminase, or by application of the A1 receptor antagonist DPCPX. Our results indicate that, in cultured rat amacrine-like neurons, the activation of A1 receptors decreases calcium influx and, thereby, inhibits [3H]ACh release.
 ...
PMID:[3H]acetylcholine release from rat amacrine-like neurons is inhibited by adenosine A1 receptor activation. 985 81


1 2 Next >>