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

---

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

A short-term incubation of isolated rat fat pads with vanadate showed the stimulated release of lipoprotein lipase (LPL) activity and suppression of the rise in extracellular adenosine level. The addition of adenosine to the medium showed inhibition of both the stimulated release of LPL activity and an increase in intracellular cAMP content by vanadate. A progressive increase in 5'-nucleotidase activity in the particulate fraction containing plasma membrane was suppressed by vanadate in a time- and dose-dependent manner, suggesting that vanadate inhibits, in part, the production of adenosine based on a dephosphorylation of AMP. In adipocytes, the inhibition of adenylate cyclase via A1 adenosine receptor is more predominant than the stimulation of adenylate cyclase via A2 adenosine receptor (Londos C. et al., Proc. Natl. Acad. Sci. U.S.A., 75, 5362-5366 (1978)). Therefore, vanadate may stimulate the release of LPL activity from the fat pads by suppressing the rise in extracellular adenosine level, accompanied by the activation of adenylate cyclase activity.
...
PMID:Involvement of adenosine in vanadate-stimulated release of lipoprotein lipase activity. 978 34

Interferon-alpha 2b (IFN-alpha 2b) can exert antiproliferative activity in both normal and malignant liver tissue. To study mechanisms of its antiproliferative action, the activity of the enzymes of adenosine metabolism were investigated. We studied 5'-nucleotidase (an adenosine-producing enzyme) and adenosine deaminase (involved in adenosine degradation). Female Wistar rats (3 weeks old) were treated with IFN-alpha 2b for 48 h, as were adult rats (3 months old) and adult rats subjected to partial hepatectomy. During IFN-alpha 2b administration, the activity of 5'-nucleotidase increased in the liver of 3-week-old rats, proportionately more than in adult rats, but the greatest increase was seen in partially hepatectomised rats. The activity of adenosine deaminase decreased in the liver of 3-week-old rats, did not change significantly in 3-month-old rats, but was significantly lower in partially hepatectomised rats. As high adenosine concentrations are toxic for mammalian cells, especially during proliferation, the progressive increase of adenosine production, together with the progressive decrease of its degradation, could be one of the mechanisms of IFN-alpha 2b-induced antiproliferative activity. In vitro studies were performed using collagenase-isolated hepatocytes. They were exposed to IFN-alpha 2b, a cAMP analogue, or both. The incubation of hepatocytes with IFN-alpha 2b did not significantly change the activity of both enzymes, whereas incubation with the cAMP analogue decreased 5'-nucleotidase activity and increased adenosine deaminase activity. The mechanism of IFN-alpha 2b-induced alteration in adenosine metabolism is therefore unclear.
...
PMID:Different responses of rat liver adenosine metabolizing enzymes during in vivo and in vitro treatment with interferon-alpha 2b. 979 20

Because epidermal growth factor (EGF) is likely to be released in the glomeruli during glomerular injury and mesangial cells possess specific receptors for EGF, we thought it to be of interest to examine whether this growth factor could influence the expression of ectoenzymes in cultured human mesangial cells. EGF stimulated 5'-nucleotidase and aminopeptidase N activities in intact human mesangial cells in a time- (24-72 h) and dose-dependent (0.1-50 ng ml(-1)) manner. Maximum stimulation represented 2.7- and 2-fold basal activities for 5'-nucleotidase and aminopeptidase N, respectively. EGF did not influence cyclic AMP production, and its effect on 5'-nucleotidase was additive to that of forskolin or 8-bromo-cAMP. In contrast, genistein (10 mg x ml(-1)), an inhibitor of tyrosine kinase, prevented EGF-dependent stimulation of aminopeptidase N and 5'-nucleotidase, suggesting that protein phosphorylation was involved in the signaling mechanism. EGF stimulated specifically the latter two enzymes since it had no effect on other ectoenzymes including alkaline phosphodiesterase I and Mg2+-ATPase activities. These results demonstrate that EGF, via the control of 5'-nucleotidase and aminopeptidase N, which are implied in adenosine formation and peptide processing, respectively, could play a role in human cultured mesangial cell contractility and proliferation.
...
PMID:Epidermal growth factor upregulates aminopeptidase N and 5'-nucleotidase in human glomerular mesangial cells. 985 17

In the rat kidney, exogenous adenosine-3'-5'-monophosphate (cAMP) is converted to adenosine via the metabolism of cAMP to adenosine-5'-monophosphate by phosphodiesterase and adenosine-5'-monophosphate to adenosine by 5'-nucleotidase. Our purpose was to investigate whether in the rat kidney adenosine is synthesized from endogenous cAMP via the same pathway. Rat kidneys were perfused with Tyrode's solution, and stabilized for 3 hr to minimize basal renal purine secretion. In control experiments (n = 6), the renal venous secretion rate of adenosine, inosine, hypoxanthine and Sigmapurines (adenosine + inosine + hypoxanthine) did not change over the two 10-min experimental periods. In contrast, the beta adrenoceptor agonist (+/-)-isoproterenol (1 and 10 microM added to the perfusate) caused a significant (1-factor analysis of variance with repeated measures; n = 31) increase in the renal venous secretion of adenosine (P <.0001), inosine (P <.0007), hypoxanthine (P <.0007) and Sigmapurines (P <.0001) as measured by high-performance liquid chromatography with ultraviolet detection. The Sigmapurines was the most discriminating index of isoproterenol-induced changes in purine release, and the renal venous secretion of Sigmapurines was significantly (2-factor analysis of variance with repeated measures) attenuated by inhibition of beta adrenoceptors with propranolol (.1 microM, n = 6; P <.05), phosphodiesterase with 3-isobutyl-1-methylxanthine (1 mM, n = 5; P <.002) and 5'-nucleotidase with alpha, beta-methyleneadenosine-5'-diphosphate (0.1 mM, n = 5; P <.03). Our data indicate that activation of beta adrenoceptors increases purine biosynthesis in the rat kidney via a mechanism that involves phosphodiesterase and 5'-nucleotidase. These results support the existence of an endogenous cAMP-adenosine pathway in the rat kidney.
...
PMID:Evidence for an endogenous cAMP-adenosine pathway in the rat kidney. 986 74

GH, in the presence of glucocorticoid, produces a delayed increase in lipolysis in rat adipose tissue, but the biochemical mechanisms that account for this action have not been established. Other lipolytic agents rapidly activate adenylyl cyclase (AC) and the resulting production of cAMP initiates a chain of reactions that culminates in the activation of hormone-sensitive lipase. We compared responses of segments of rat epididymal fat or isolated adipocytes to 30 ng/ml GH and 0.1 microg/ml dexamethasone (Dex) with 0.1 ng/ml isoproterenol (ISO), which evoked a similar increase in lipolysis. All measurements were made during the fourth hour after the addition of GH+Dex or immediately after the addition of ISO to cells or tissues that had been preincubated for 3 h without hormone. Although no significant increases in cAMP were discernible in homogenates of GH+Dex-treated tissues, Rp-cAMPS (Rp-adenosine 3'5'-phosphothioate), a competitive inhibitor of cAMP, was equally effective in decreasing lipolysis induced by GH+Dex or ISO. The proportion of PKA that was present in the active form was determined by measuring the incorporation of 32P from [gamma-32P]ATP into kemptide in the absence and presence of saturating amounts of cAMP. GH+Dex and ISO produced similar increases in protein kinase A activity in tissue extracts. Treatment with GH+Dex did not change the total forskolin-stimulated AC present in either a crude membrane pellet sedimented at 16K x g or a less dense membrane pellet sedimented at 100K x g, but doubled the AC activity in the 16K pellet when assayed in the absence of forskolin. To evaluate possible effects on G proteins, pellets obtained from centrifugation of adipocyte homogenates at 16K x g and 100K x g were solubilized and subjected to PAGE and Western analysis. GH+Dex decreased Gi alpha2 by 44% (P < 0.02) in the 16K pellets and increased it by 52% (P < 0.01) in the 100K pellets. Gs alpha in the 16K pellet was unaffected by GH+Dex and was decreased (P < 0.05) in the 100K pellet. Sucrose density fractionation of the 16K pellets revealed a similar GH+Dex-dependent shift of Gi alpha2 to less dense fractions as determined by both Western analysis and [32P]NAD ribosylation catalyzed by pertussis toxin. No such changes were seen in the distribution of Gs alpha or 5'-nucleotidase. Colchicine (100 microM) blocked the GH+Dex-dependent shift of Gi alpha2 from the 16K to the 100K pellet and blocked the lipolytic effects of GH+Dex, but not those of ISO. We conclude that by modifying the relationship between AC and Gi alpha2, GH+Dex relieves some inhibition of cAMP production and consequently increases lipolysis.
...
PMID:Growth hormone and dexamethasone stimulate lipolysis and activate adenylyl cyclase in rat adipocytes by selectively shifting Gi alpha2 to lower density membrane fractions. 1006 47

The mechanism underlying beta,gamma-methylene ATP (beta,gamma-MeATP)-induced cAMP elevation was investigated in rat glioma C6Bu-1 cells. Beta,gamma-MeATP increased forskolin-stimulated cAMP formation in a manner sensitive to both the P1 antagonist xanthine amine congener (XAC) and the P2 antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Adenosine deaminase (ADA; 1 U/mL), which abolished the adenosine-induced response, did not eliminate the beta,gamma-MeATP-induced response. However, combination of ADA with alpha,beta-methylene ADP (alpha,beta-MeADP), an ecto-5'-nucleotidase inhibitor, blocked the beta,gamma-MeATP-induced response. AMP, the substrate for ecto-5'-nucleotidase, also induced cAMP formation in a manner sensitive to XAC and alpha,beta-MeADP inhibition. However, the AMP-induced response was not blocked by PPADS. HPLC analyses revealed that adenosine was generated from beta,gamma-MeATP and AMP. In addition, alpha,beta-MeADP inhibited the conversion of beta,gamma-MeATP and AMP to adenosine, whereas PPADS blocked adenosine formation from beta,gamma-MeATP but not from AMP. [3H]Adenosine generated from [3H]AMP was preserved on the cell surface environment even in the presence of ADA. The mRNAs for ecto-phosphodiesterase/pyrophosphatase 1 (EC 3.1.4.1), ecto-5'-nucleotidase (EC 3.1.3.5) and adenosine A2B receptor were detected by RT-PCR. These results suggest that C6Bu-1 cells possess ecto-enzymes converting beta,gamma-MeATP to adenosine, and the locally accumulated adenosine in this mechanism efficiently stimulates A2B receptors in a manner resistant to exogenous ADA.
...
PMID:Beta,gamma-methylene ATP-induced cAMP formation in C6Bu-1 cells: involvement of local metabolism and subsequent stimulation of adenosine A2B receptor. 1115 59

ATP causes relaxation of the K(+)-contracted rat vas deferens. Possible sites of action were investigated. ATP and adenosine relaxed the vas deferens precontracted with 80 mM K(+); EC(50) values and maximal relaxations averaged, respectively, 760 microM and 56% for ATP and 74 microM and 30% for adenosine. The adenosine P1 receptor antagonist 8-(para-sulfophenyl)theophylline (8-SPT) reduced relaxations caused by adenosine and low concentrations of ATP, as did the Rp-diastereomer of adenosine 3',5'-cyclic phosphorothioate (Rp-cAMPS), an inhibitor of protein kinase A. The phosphodiesterase inhibitor 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724) augmented responses to adenosine and low concentrations of ATP. alpha,beta-Methylene ADP, an inhibitor of 5'-nucleotidase, reduced relaxations caused by ATP to a similar extent as did 8-SPT. In the presence of an almost saturating concentration of adenosine, ATP caused further relaxation. Conversely, in the presence of ATP, adenosine had little effect. Like ATP, UTP and other nucleoside triphosphates relaxed the vas deferens. The P2 receptor antagonists reactive blue 2, acid blue 25 and 4,4'-diisothiocyanotostilbene-2,2'-disulphonate (DIDS) attenuated the relaxation caused by ATP; suramin, pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS), Evans blue, trypan blue, reactive red 2 and brilliant blue G had no effect. Three non-selective inhibitors of protein kinases, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), staurosporine and (8R*,9S*,11S*)-(-)-9-hydroxy-9-carboxy-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one (K-252b), markedly reduced the relaxation caused by ATP. The results indicate that adenosine, derived from enzymatic dephosphorylation, contributes to the relaxant effect of ATP, presumably by activation of a smooth muscle adenosine receptor linked to the accumulation of cAMP and activation of protein kinase A. Yet, the main part of the response to ATP is mediated by a site distinct from the adenosine receptor. The pharmacological properties of this site differ from known P2 receptor subtypes. Possibly, the nucleotide-evoked relaxation is due to a phosphoryl transfer catalyzed by an ecto-protein kinase.
...
PMID:Nucleotide-evoked relaxation of rat vas deferens: possible mechanisms. 1183 57

CD73 (ecto-5'-nucleotidase; EC 3.1.3.5) participates in lymphocyte binding to endothelial cells and converts extracellular AMP into a potent anti-inflammatory substance adenosine. However, the regulation of expression and function of CD73 has remained largely unknown. In this study, we show that IFN-alpha produces a time- and dose-dependent long-term up-regulation of CD73 on endothelial cells, but not on lymphocytes both at protein and RNA levels. Moreover, CD73-mediated production of adenosine is increased after IFN-alpha treatment on endothelial cells, resulting in a decrease in the permeability of these cells. Subsequent to induction with PMA, FMLP, dibutyryl cAMP, thrombin, histamine, IL-1beta, TNF-alpha, and LPS, no marked changes in the level of CD73 expression on endothelial cells are observed. We also show that CD73 is up-regulated in vivo on the vasculature after intravesical treatment of urinary bladder cancers with IFN-alpha. In conclusion, distinct behavior of lymphocyte and endothelial CD73 subsequent to cytokine treatment further emphasizes the existence of cell type-specific mechanisms in the regulation of CD73 expression and function. Overall, these results suggest that IFN-alpha is a relevant in vivo regulator of CD73 in the endothelial-leukocyte microenvironment in infections/inflammations, and thus has a fundamental role in controlling the extent of inflammation via CD73-dependent adenosine production.
...
PMID:IFN-alpha induced adenosine production on the endothelium: a mechanism mediated by CD73 (ecto-5'-nucleotidase) up-regulation. 1473 46

Adenosine appears to be an endogenous somnogen. The lateral dorsal tegmental/pedunculopontine nucleus (LDT/PPT) located in the mesopontine tegmentum is important in the regulation of arousal. Neurons in this nucleus are strongly hyperpolarized by adenosine and express neuronal nitric oxide synthase. Zaprinast is a cyclic nucleotide phosphodiesterase inhibitor, and has been shown in the hippocampal slice to inhibit the field excitatory postsynaptic potential. This action could be blocked by an adenosine receptor antagonist, and therefore is presumably due to adenosine release stimulated by zaprinast. In the present study we tested the effect of zaprinast on extracellular adenosine accumulation in pontine slices containing the LDT. Zaprinast at 10 microM evoked an increase in extracellular adenosine concentration. This effect was blocked by impermeant inhibitors of 5'-nucleotidase, indicating that the extracellular adenosine was derived from extracellular AMP. However, inhibitors of cAMP degradation had little or no effect on zaprinast-evoked adenosine accumulation, suggesting that extracellular cAMP was not the source. Removal of extracellular calcium inhibited the effect of zaprinast. These results demonstrate that a pathway exists by which zaprinast stimulates extracellular adenosine accumulation, and the presence of this pathway in the pontine slice suggests the possibility that it may be relevant for the regulation of behavioral state.
...
PMID:Zaprinast stimulates extracellular adenosine accumulation in rat pontine slices. 1550 Sep 58

Cyclic AMP (cAMP) appears extracellularly in a variety of tissues including brain, liver, and kidney; whether it appears in adipose tissue and responds to physiological perturbation is unknown. The purpose of this study was to examine adipose tissue extracellular cAMP appearance and metabolism in situ and in vitro in physiologically challenged animals. Littermate swine were either sedentary or exercise trained on a treadmill for 3 months and subjected to acute exercise on experiment day. In situ, microdialysis probes in subcutaneous back fat were perfused before, during, and after animals performed 20 mins of acute exercise, and dialysate was analyzed for cAMP and adenosine. In vitro, isolated adipocytes were hormonally stimulated to provoke cAMP synthesis and efflux, and plasma membrane phosphodiesterase and 5'-nucleotidase activities were measured. Extracellular cAMP and adenosine levels in adipose tissue of sedentary swine averaged 5.2 +/- 1.7 and 863 +/- 278 nM, respectively. Exercise training tended to increase extracellular cAMP (11.3 +/- 1.7 nM) and reduce extracellular adenosine (438 +/- 303 nM), although neither change was statistically significant. Acute exercise caused a significant 3-fold and 16-fold increase in extracellular cAMP and adenosine, respectively, compared to rest. These changes occurred despite a 2- to 3-fold increase in adipose tissue blood flow during acute exercise. In vitro, cAMP efflux from exercise-trained swine was 42% greater than that from adipocytes of sedentary swine, yet adipocyte plasma membranes from exercise-trained and sedentary swine did not differ in maximal phosphodiesterase and 5'-nucleotidase activities. We conclude that cAMP appears extracellularly in swine adipose tissue and that the levels of extracellular cAMP and adenosine in intact swine adipose tissue are influenced by both acute and chronic exercise. The subsequent impact of the changes in these biochemicals on local cellular metabolism and growth remains to be determined.
...
PMID:Extracellular cyclic AMP and adenosine appearance in adipose tissue of Sus scrofa: effects of exercise. 1552 38


<< Previous 1 2 3 4 5 6 Next >>

---