Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several lines of evidence indicate that ATP may play an important role in Long-Term Potentiation. In this investigation we evaluated the effect of a memory task (step-down inhibitory avoidance) on the synaptosomal ecto-enzymes (ATP diphosphohydrolase and 5'-nucleotidase) involved in the degradation of ATP to adenosine. After the training session, a decrease in the ATPase (40%) and ADPase (29%) activities of ATP diphosphohydrolase as well as was a decrease in 5'-nucleotidase activity (31%) was observed in hippocampal synaptosomes of rats trained and killed immediately after training. In synaptosomes of rats killed 30 minutes after training, a decrease in ATPase activity (28%) was observed. In the test session, no significant changes were observed in the enzyme activities studied. These results provide new information about the activity of ecto-enzymes involved in nucleotide degradation and their possible participation in mechanisms of acquisition and modulation of memory processing.
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PMID:Inhibitory avoidance learning inhibits ectonucleotidases activities in hippocampal synaptosomes of adult rats. 969 Jul 40

Extracellular ATP, when added as a single dose at concentrations higher than 0.1 mM to the culture medium, was growth inhibitory or even cytotoxic for human epidermoid carcinoma cells (A431). Adenosine at the same concentrations was much less potent. The molecular mechanism underlying the inhibitory effect of extracellular ATP has been investigated. The cytostatic as well as the cytotoxic effects of ATP could be prevented by supplying uridine as a pyrimidine source and, alternatively, by simultaneous addition of dipyridamole, which inhibits the uptake of adenosine. The data suggest that the long-term production and continuous uptake of adenosine, which is enzymatically generated from the ATP in the medium, led to an intracellular nucleotide imbalance with pyrimidine starvation. This triggered suicidal processes ending up in apoptosis of the cells. The tumor cells have been adapted to extracellular ATP with the aim to obtain cells which are more resistant to ATP. Therefore, growing cells were periodically treated with extracellular ATP. These cells were characterized by an enlargement of cell size, a decreased proliferation rate, and a reduced but not abolished sensitivity to cytostatic and cytotoxic ATP doses. The calcium response of adapted cells was shortened. The nucleotide hydrolyzing ectoenzyme activities (ecto-ATPase, ecto-ADPase, ecto-AMPase, ecto-Ap4Aase) were simultaneously upregulated. All phenotypic alterations of the adapted cells disappeared after cultivation for several generations in the absence of extracellular ATP. Considering ATP as a potential chemotherapeutic agent the adaptive phenomena of treated cells might be important.
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PMID:Nucleotide metabolizing ectoenzymes are upregulated in A431 cells periodically treated with cytostatic ATP leading to partial resistance without preventing apoptosis. 973 53

Inhibitory effects of various purinergic compounds on the Mg(2+)-dependent enzymatic hydrolysis of [(3)H]ATP in rat liver plasma membranes were evaluated. Rat liver enzyme ecto-ATPase has a broad nucleotide-hydrolyzing activity, displays Michaelis-Menten kinetics with K(m) for ATP of 368+/-56 microM and is not sensitive to classical inhibitors of the ion-exchange and intracellular ATPases. P2-antagonists and diadenosine tetraphosphate (Ap(4)A) progressively and non-competitively inhibited ecto-ATPase activity with the following rank order of inhibitory potency: suramin (pIC(50), 4.570)>Reactive blue 2 (4.297)&z.Gt;Ap(4)A (3. 268)>pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (2. 930). Slowly hydrolyzable P2 agonists ATPgammaS, ADPbetaS, alpha, beta-methylene ATP and beta,gamma-methylene ATP as well as the diadenosine polyphosphates Ap(3)A and Ap(5)A did not exert any inhibitory effects on the enzyme activity at concentration ranges of 10(-4)-10(-3) M. Thin-layer chromatography analysis of the formation of [(3)H]ATP metabolites indicated the presence of other enzyme activities on liver surface (ecto-ADPase and 5'-nucleotidase), participating in concert with ecto-ATPase in the nucleotide hydrolysis through the stepwise reactions ATP-->ADP-->AMP-->adenosine. A similar pattern of sequential [(3)H]ATP dephosphorylation still occurs in the presence of ecto-ATPase inhibitors suramin, Ap(4)A and PPADS, but the appearance of the ultimate reaction product, adenosine, was significantly delayed. In contrast, hydrolysis of [(3)H]ATP in the presence of Reactive blue 2 only followed the pattern ATP-->ADP, with formation of the subsequent metabolites AMP and adenosine being virtually eliminated. These data suggest that although nucleotide-binding sites of ecto-ATPase are distinct from those of P2 receptors, some purinergic agonists and antagonists can potentiate cellular responses to extracellular ATP through non-specific inhibition of the ensuing pathways of purine catabolism.
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PMID:Inhibitory effects of some purinergic agents on ecto-ATPase activity and pattern of stepwise ATP hydrolysis in rat liver plasma membranes. 1082 45

Cell surface ecto-nucleotidases are considered the major effector system for inactivation of extracellular adenine nucleotides, whereas the alternative possibility of ATP synthesis has received little attention. Using a TLC assay, we investigated the main exchange activities of 3H-labeled adenine nucleotides on the cultured human umbilical vein endothelial cells. Stepwise nucleotide degradation to adenosine occurred when a particular nucleotide was present alone, whereas combined cell treatment with ATP and either [3H]AMP or [3H]ADP caused unexpected phosphorylation of 3H-nucleotides via the backward reactions AMP --> ADP --> ATP. The following two groups of nucleotide-converting ecto-enzymes were identified based on inhibition and substrate specificity studies: 1) ecto-nucleotidases, ATP-diphosphohydrolase, and 5'-nucleotidase; 2) ecto-nucleotide kinases, adenylate kinase, and nucleoside diphosphate kinase. Ecto-nucleoside diphosphate kinase possessed the highest activity, as revealed by comparative kinetic analysis, and was capable of using both adenine and nonadenine nucleotides as phosphate donors and acceptors. The transphosphorylation mechanism was confirmed by direct transfer of the gamma-phosphate from [gamma-32P]ATP to AMP or nucleoside diphosphates and by measurement of extracellular ATP synthesis using luciferin-luciferase luminometry. The data demonstrate the coexistence of opposite, ATP-consuming and ATP-generating, pathways on the cell surface and provide a novel mechanism for regulating the duration and magnitude of purinergic signaling in the vasculature.
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PMID:Extracellular ATP formation on vascular endothelial cells is mediated by ecto-nucleotide kinase activities via phosphotransfer reactions. 1114 13

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization by activation of neuronal adenosine A(1) receptors, suppressing acetylcholine release from motor neurons and excitatory neurotransmitters from central sites. It also exacerbates venom-induced hypotension by activating A(2) receptors in the vasculature. Adenosine and inosine both activate mast cell A(3) receptors, liberating vasoactive substances and increasing vascular permeability. Guanosine probably contributes to hypotension, by augmenting vascular endothelial cGMP levels via an unknown mechanism. Novel functions are suggested for toxins that act upon blood coagulation factors, including nitric oxide production, using the prey's carboxypeptidases. Leucine aminopeptidase may link venom hemorrhagic metalloproteases and endogenous chymotrypsin-like proteases with venom L-amino acid oxidase (LAO), accelerating the latter. The primary function of LAO is probably to promote prey hypotension by activating soluble guanylate cyclase in the presence of superoxide dismutase. LAO's apoptotic activity, too slow to be relevant to prey capture, is undoubtedly secondary and probably serves principally a digestive function. It is concluded that the principal function of L-type Ca(2+) channel antagonists and muscarinic toxins, in Dendroaspis venoms, and acetylcholinesterase in other elapid venoms, is to promote hypotension. Venom dipeptidyl peptidase IV-like enzymes probably also contribute to hypotension by destroying vasoconstrictive peptides such as Peptide YY, neuropeptide Y and substance P. Purines apparently bind to other toxins which then serve as molecular chaperones to deposit the bound purines at specific subsets of purine receptors. The assignment of pharmacological activities such as transient neurotransmitter suppression, histamine release and antinociception, to a variety of proteinaceous toxins, is probably erroneous. Such effects are probably due instead to purines bound to these toxins, and/or to free venom purines.
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PMID:Ophidian envenomation strategies and the role of purines. 1173 31

Extracellular ATP and adenosine modulate synaptic transmission in hippocampal neurons. ATP released from neural cells is hydrolyzed to adenosine by a chain of ecto-nucleotidases. ATP diphosphohydrolase hydrolyses ATP and ADP nucleotides to AMP and 5'-nucleotidase hydrolyses AMP to adenosine. In this work, we investigated the ATPase and ADPase activities of ATP diphosphohydrolase in cultured hippocampal neurons. The apparent Michaelis-Menten constant (K(m)) was 233.9 +/- 14.6 and 221.8 +/- 63.6 microM, with a calculated maximal velocity (V(max), approximately) of 49.2 +/- 10.7 and 10.9 +/- 5.2 nmol Pi/mg protein/min for ATP and ADP, respectively. The horizontal straight line obtained in the competition plot indicated that only one active site is able to hydrolyze both substrates. Furthermore, we detected the presence of this enzyme using anti-CD39 antibody, which strongly stained the soma of pyramidal and bipolar neurons, but the neurites connecting the cell clusters were also immunopositive. This antibody recognized three bands with a molecular mass close to 95, 80 and 60kDa in immunoblotting analysis. The present results show, for the first time, the kinetic and immunocytochemical characterization of an ATP diphosphohydrolase in cultured hippocampal neurons. Probably, the widespread distribution of this enzyme on the surface of neurons in culture could reflect its functional importance in studies of synaptic plasticity hippocampal.
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PMID:Kinetic characterization and immunodetection of ecto-ATP diphosphohydrolase (EC 3.6.1.5) in cultured hippocampal neurons. 1182 Nov 53

We have previously observed that, while acute stress induces analgesia, chronic stress causes a hyperalgesic response in male rats. No effect was observed in females. There is increasing evidence that both ATP and adenosine can modulate pain. Extracellular ATP and ADP are hydrolyzed by an apyrase in synaptosomes from the peripheral and central nervous systems. In the present study, we investigated the effect of chronic and acute stress on ATPase-ADPase and 5'-nucleotidase activities in spinal cord of male and female rats. Adult male and female Wistar rats were submitted to 1 h restraint stress/day for 1 day (acute) or 40 days (chronic) and were sacrificed 24 h later. ATPase-ADPase activities were assayed in the synaptosomal fraction obtained from the spinal cord of control and stressed animals. ADP hydrolysis was decreased 25% in chronically stressed males, while no change was observed on ATPase activity. There was an increase in the 5'-nucleotidase activity in the same group. No effect on ADPase, ATPase or on 5'-nucleotidase activity was observed in females with chronic stress, or after acute stress neither in males or females. Chronic stress reduced ADP hydrolysis and increased 5'-nucleotidase activity in the spinal cord in male rats.
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PMID:Effect of chronic and acute stress on ectonucleotidase activities in spinal cord. 1189 Sep 46

In the present report we describe an NTPDase 1 (ATP diphosphohydrolase; ecto-apyrase; EC 3.6.1.5) in rat hippocampal slices. The effect of glutamate on the ATPase and ADPase activities in rat hippocampal slices of different ages was also studied since adenosine, the final product of an enzymatic chain that includes NTPDase 1 and 5'-nucleotidase, can act upon A1 receptors in turn decreasing the release of glutamate. Hippocampal slices from 7, 14, 20-23 and 60 day-old rats were prepared and ATPase and ADPase activities were measured. The parallelism of ATPase and ADPase activities in all parameters tested indicated the presence of an ATP diphosphohydrolase. In addition, a Chevillard plot indicated that ATP and ADP are hydrolyzed at the same active site on the enzyme. ATPase activity was significantly activated by glutamate in 20-23 and 60 day-old rats, but ADPase activity was not activated. These results could indicate distinct behavior of the ATPase and ADPase activities of NTPDase 1 in relation to glutamate or the simultaneous action of the ecto-ATPase. Activation of ATPase activity by glutamate may constitute an important role in this developmental period, possibly protecting against the neurotoxicity induced by ATP, as well as producing high levels of ADP, by increasing adenosine production, a neuroprotective compound.
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PMID:ATP diphosphohydrolase (NTPDase 1) in rat hippocampal slices and effect of glutamate on the enzyme activity in different phases of development. 1203 90

ATPase and ADPase activities capable of hydrolyzing nucleoside di- and triphosphates in the presence of Ca2+ are present in synovial membrane of metacarpophalangeal joint mainly associated to membrane fractions. These hydrolytic activities have been considered involved in the inflammatory process where ATP and ADP are inflammatory mediators while adenosine counteracts this effect. Both, subcellular localization and kinetic properties of these nucleotidase activities, suggest that could correspond to single enzyme called ATP-diphosphohydrolase or apyrase. The comparison of the activity on ATP-Ca and ADP-Ca from normal and pathological equine synovial membrane did not show significant differences either in the subcellular fraction distribution or in the enrichment of each subcellular fraction. Neither differences on 5'-nucleotidase activity present in the microsomal fraction were observed.
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PMID:ATPase and Adpase activities in synovial membrane of equine metacarpophalangeal joint. 1215 Feb 8

It has been demonstrated in anti-Thy1 glomerulonephritis that extracellular adenine nucleotides have a significant pro-inflammatory activity, however, glomerular ATP/ADPase, which in concert with 5'-nucleotidase converts ATP/ADP, and AMP to anti-inflammatory adenosine had an anti-inflammatory role. We have studied distribution of 5'-nucleotidase and divalent cation-activated ATPase in kidney biopsies of 15 patients with glomerulonephritis. The major finding was an overexpression of 5'-nucleotidase in the mesangium of kidney from patients with membranous nephropathy. No change in 5'-nucleotidase expression was observed in other common forms of glomerulonephritis: IgA nephropathy, mesangioproliferative and mesangiocapillary glomerulonephritis. The distribution of Mg(2+)-ATPase in investigated specimens was similar to control distribution. Results obtained in this study indicate increased mesangial expression of 5'-nucleotidase in non-proliferative form of glomerulonephritis consistent to a role of mesangial cells in inflammatory processes.
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PMID:Increased expression of glomerular mesangial cell 5'-nucleotidase in membranous nephropathy. 1218 7


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