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)

This study was aimed to determine whether singlet oxygen (1O2) attenuates 5'-nucleotidase activity in the ischemic myocardium. Isolated rat hearts were exposed to either exogenous 1O2 produced by irradiating rose bengal or 40-min ischemia and reperfusion. Ecto-5'-nucleotidase activity was inhibited by exogenous 1O2 (3.74 +/- 0.38 mumol/min/g dry weight), when compared with normal control (7.52 +/- 0.41 mumol/min/g dry weight; P < 0.05). The enzymatic activity was significantly preserved by histidine (25 mM)--a 1O2 scavenger (7.04 +/- 0.61 mumol/min/g dry weight; P < 0.05 v rose bengal group). After ischemia, the activity of ecto-5'-nucleotidase was greatly reduced (2.51 +/- 0.25 mumol/min/g dry weight), when compared with normal control. Histidine significantly enhanced ecto-5'-nucleotidase activity (6.55 +/- 0.52 mumol/min/g dry weight, P < 0.05 v ischemic control). Adenosine release was consistent with ecto-5'-nucleotidase activity. The time course studies of effects of 1O2 on coronary flow, cardiac function, and LDH release revealed that the damage by 1O2 to ecto-5'-nucleotidase activity and adenosine release primarily accounted for impaired coronary flow, cardiac dysfunction, and impaired cardiac metabolism. Lipid peroxidation induced by exogenous 1O2 or ischemia was in parallel with ecto-5'-nucleotidase deactivation by 1O2. It is concluded that 1O2 causes inactivation of ecto-5'-nucleotidase and attenuation of adenosine release which could possibly be one of the important mechanisms of oxygen radical-mediated myocardial injury.
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PMID:Interaction of singlet oxygen with 5'-nucleotidase in rat hearts. 859 96

Adenosine is an important inhibitory neuromodulator in the cerebral cortex, yet it remains unclear how extracellular adenosine concentrations are regulated. Recently, it has been shown that beta-adrenergic receptor stimulation in rat cortical cultures causes the accumulation of extracellular adenosine derived by enzymatic hydrolysis from adenosine cyclic monophosphate (cAMP) transported into the extracellular space. In this study we show that vasoactive intestinal peptide (VIP), in addition to activating adenylyl cyclase and promoting the accumulation of intracellular cAMP in rat cortical cultures, also causes transport of cAMP and accumulation of extracellular adenosine. We further show that the extracellular accumulation of adenosine in response to VIP can be blocked by inhibition of cAMP transport, cyclic nucleotide phosphodiesterase activity, and 5'-nucleotidase, indicating that extracellular cAMP is the source of the adenosine. Cyclic AMP transport may be a general mechanism by which a variety of neuromodulators that act upon receptors coupled to adenylyl cyclase might regulate extracellular adenosine levels and thereby inhibitory tone in the cerebral cortex.
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PMID:Vasoactive intestinal peptide regulates extracellular adenosine levels in rat cortical cultures. 861 71

Adenosine has been implicated in the regulation of rapid eye movement sleep (REMS). In an attempt to understand the mechanism of production of adenosine in relation to REMS it was hypothesized that should it be involved in REMS, the latter's deprivation is likely to affect its synthetic machinery. Hence, male albino rats were deprived of REMS by the flower pot technique and the activity of 5'-nucleotidase, an enzyme responsible for adenosine synthesis, was estimated in the cerebrum, cerebellum and brain stem. Suitable control experiments were conducted to rule out the non-specific effects. The results showed that 5'-nucleotidase activity decreased only after 4 days deprivation and in the cerebrum only; while short-term (2 days) deprivation did not affect the enzyme activity in any of the brain areas. The altered enzyme activity returned to baseline level after recovery from REMS deprivation. The results from other control experiments suggested that the effects were primarily due to REMS deprivation and not due to non-specific factors. It is proposed that if adenosine is involved in REMS, its production is unlikely to depend on 5'-nucleotidase or it may account primarily for EEG desynchronization.
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PMID:Effect of rapid eye movement sleep deprivation on 5'-nucleotidase activity in the rat brain. 871 Jan 80

At the neuromuscular junction and possibly also at the synaptic level in the brain, the main sequence of events (see Fig. 5) that involves purines in modulation of ACh release includes the following observations: (1) storage of ATP and its release either together with, or independently of acetylcholine. ATP is also released from the post-junctional component. Adenosine as such is released either from the motor nerve terminals or from the post-junctional component. (2) There is extracellular hydrolysis of ATP to adenosine, which is the active substance to modulate transmitter release. The key enzyme in the conversion of AMP into adenosine is the ecto 5'-nucleotidase. When ecto-5'-nucleotidase is not available (e.g. in cholinergic nerve terminals of the cerebral cortex) ATP as such exerts the neuromodulatory role normally fulfilled by adenosine. (3) Both the inhibition and the excitation induced by adenosine on ACh release in the rat is inactivated through up-take and deamination. (4) Adenosine-induced inhibition of ACh release is mediated via A1 receptors and the excitation via A2a receptors. The A2a receptors are positively coupled to the adenylate cyclase/cyclic AMP system, whereas the presynaptic A1 receptors (a) may be negatively linked to adenylate cyclase and (b) to phospholipase C, and, upon stimulation, (c) increase potassium conductance and (d) decrease calcium conductance. (5) Activation of A2a receptors is essential for substances that facilitate ACh release (e.g. CGRP, forskolin) to exert their effects, as well as for induction of nicotinic autofacilitatory receptor desensitization. (6) There are interactions between A1 and A2a receptors. Thus, the net adenosine neuromodulatory response is the resultant, at each moment, of the relative degree of activation of each one of these receptors. This relative activation depends upon the intensity (frequency, pulse duration) of stimulation of the motor nerve terminals. (7) Adenosine released as such seems to preferentially activate A1 receptors, whereas the adenosine formed from metabolism of adenine nucleotides prefers to activate the A2a receptors. In conclusion, to find out precisely what occurs with ACh in transmitting its message at the synaptic level, one has to consider the subtle ways used by purines to modulate the ACh response. It therefore appears of interest that pharmacological and therapeutic strategies use this knowledge to approach cholinergic transmission deficiencies based upon reduction of ACh release.
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PMID:Purinergic regulation of acetylcholine release. 900 12

Ectonucleotidases are enzymes that degrade extracellular nucleotides. Extracellular nucleotides (especially ATP) and their degradation products (particularly adenosine) have multiple effects on cell functions by acting through purinergic receptors. Adenosine nucleotides are present in bile, which suggests that hepatocytes may release nucleotides into the canaliculus where they are promptly degraded into adenosine by ecto-ATPase and 5'-nucleotidase, which have been identified in the canalicular plasma membrane. Adenosine is then transported into hepatocytes by a Na+-dependent nucleoside transporter that is present in the canalicular plasma membrane. Purification and molecular cloning of ecto-ATPase and other canalicular proteins are complicated by an abundant canalicular plasma membrane protein, cCAM 105. However, the recent cloning of an ecto-ATPase (apyrase) from potato tubers provides a new opportunity to identify the canalicular ecto-ATPase. The canalicular Na+-dependent purine nucleoside transporter has been cloned from rat liver. Study of its expression during development and other physiological circumstances suggests that the transporter may play an important role in maintaining hepatic purine levels that are essential for the liver to serve as a major source of purines for tissues (i.e., brain, muscle) that lack pathways for de novo purine biosynthesis.
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PMID:Ectonucleotidases, purine nucleoside transporter, and function of the bile canalicular plasma membrane of the hepatocyte. 903 51

Adenosine has potent immunosuppressive activity. Since the source of adenosine and the mechanism of its release in the immune system is largely unknown and may vary according to cell type, we have evaluated the relationship between adenosine metabolism and the enzymatic activities and mRNA levels of adenosine-metabolizing enzymes in myeloid and lymphoid cell lines. Induction of HL-60 cell differentiation along the macrophage lineage by PMA resulted in a reduction in the activities of adenosine deaminase (ADA), adenosine kinase (AK), and inosine monophosphate-specific cytosolic 5'-nucleotidase and an elevation of ecto-5'-nucleotidase (ecto-5'-NT). These changes were accompanied by an elevation of ecto-5'-NT mRNA and a decrease in ADA and AK mRNAs in a time-dependent fashion. Comparison of AK and ADA mRNA levels in several other leukemic cell lines revealed generally similar responses to PMA with much stronger suppression in immature T cells than in B cells. The metabolism of adenosine either through phosphorylation (AK) or deamination (ADA) was reduced in PMA-stimulated cells. Furthermore, the cumulative changes in enzyme expression resulted in a 2.5-fold increase in intracellular adenosine formation in PMA-stimulated cells. The inhibition of AK by 5'-iodotubercidin further increased adenosine formation by 6-fold over that in untreated cells. In accord with the increase in ecto-5'-NT activity, extracellular AMP dephosphorylation increased dramatically, but there was no increase in extracellular ATP degradation. These results indicate that a coordinated shift in adenosine-metabolizing enzyme levels during PMA-induced HL-60 cell differentiation is accompanied by a decrease in adenosine uptake and an increase in adenosine release.
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PMID:Adenosine metabolism during phorbol myristate acetate-mediated induction of HL-60 cell differentiation: changes in expression pattern of adenosine kinase, adenosine deaminase, and 5'-nucleotidase. 914 13

1. Adenosine exerts cardioprotective effects on the ischaemic myocardium. The production of adenosine in the ischaemic myocardium is attributed primarily to the enzymatic dephosphorylation of adenosine 5'-monophosphate (AMP) by 5'-nucleotidase. We determined the activity of 5'-nucleotidase in rat hearts. The objective of the study was to determine the effects of ATP-sensitive K+ (K[ATP]) channel antagonists (glibenclamide and 5-hydroxydecanoate) on the production of adenosine, by use of a flexibly mounted microdialysis technique. 2. Rats were anaesthetized and the microdialysis probe was implanted in the left ventricular myocardium, followed by perfusion with Tyrode solution. The baseline level of dialysate adenosine was 0.51 +/- 0.09 microM (n = 16). Introduction of AMP (100 microM) through the probe increased the dialysate adenosine markedly to 9.79 +/- 0.43 microM (n = 12, P < 0.001 vs baseline), and this increase was inhibited by the ecto-5'-nucleotidase inhibitor, alpha,beta-methyleneadenosine 5'-diphosphate (100 microM), to 0.76 +/- 0.12 microM (n = 8). Thus, the dialysate adenosine noted during the perfusion of AMP originated from dephosphorylation of AMP by ecto-5'-nucleotidase, and the dialysate level of adenosine attained reflects the ecto-5'-nucleotidase activity in the tissue in situ. 3. Glibenclamide (0.1-100 microM) decreased the adenosine concentration measured during the perfusion of AMP (100 microM) in a concentration-dependent manner (IC50 = 10.5 microM). In contrast, 5-hydroxydecanoate (10-100 microM) did not affect the concentrations of dialysate adenosine, measured in the presence of AMP (100 microM). These results suggest that glibenclamide inhibits the activity of endogenous ecto-5'-nucleotidase and decreases the concentration of adenosine in the interstitial space of rat ventricular muscles in situ.
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PMID:The effect of glibenclamide on the production of interstitial adenosine by inhibiting ecto-5'-nucleotidase in rat hearts. 937 55

During ischaemia and hypoxia adenosine is released from cardiac cells. Adenosine is the end product of 5'-nucleotidase activity. We were interested in how this enzyme activity in plasma of patients with unstable angina pectoris, causes short-term ischaemia. 5'-Nucleotidase activity in plasma was determined using a standard diagnostic kit from Sigma. Furthermore, we studied the activity of adenosine deaminase in plasma, granulocytes, lymphocytes and erythrocytes by the methods of Hopkinson [1]. It was found that 5'-nucleotidase activity was increased by about 43% in plasma. The activity of adenosine deaminase (ADA) in plasma increased by 6%, but in granulocytes, lymphocytes and erythrocytes decreased by about 24, 19 and 10.6%, respectively. We concluded that a large increase in 5'-nucleotidase activity may be caused by activation of 5'-ectonucleotidase in blood cells by ischaemia. However, the decrease in ADA activity in blood cells may be associate with the adenosine metabolism.
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PMID:5'-nucleotidase and adenosine deaminase activities in blood of patients with unstable angina pectoris. 940 66

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

Adenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) and adenosine 5',5"'-P1,P5-pentaphosphate (Ap5A) are stored in and released from rat brain synaptic terminals. In the present study we investigated the hydrolysis of dinucleotides (Ap4A and Ap5A) in synaptosomes from the cerebral cortex of adult rats. Ap4A and Ap5A, but not Ap3A, were hydrolyzed at pH 7.5 in the presence of 20 mM Tris/HCl, 2.0 mM MgCl2, 10 mM glucose and 225 mM sucrose at 37 degrees C. The disappearance of the substrates measured by FPLC on a mono-Q HR column was both time and protein dependent. Since synaptosome integrity was at least 90% at the end of the assay, hydrolysis probably occurred by the action of an ecto-enzyme. Extracellular actions of adenine dinucleotides at central nervous system terminate due to the existence of ecto-nucleotidases which specifically cleave these dinucleotides. These enzymes in association with an ATP diphosphohydrolase and a 5'-nucleotidase are able to promote the complete hydrolysis of dinucleotides to adenosine in the synaptic cleft.
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PMID:Catabolism of Ap4A and Ap5A by rat brain synaptosomes. 995 47


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