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:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rat fat cells incubated for 15 min at 37 degrees and pH 8.5, glycerol release was highly stimulated both by norepinephrine and by theophylline. Prostacyclin (PGI2) (10(-8)-10(-7)M) did not alter the basal rate of glycerol release but potentiated the lipolytic effect of 2 X 10(-6)M norepinephrine. The rate of norepinephrine-induced glycerol release was increased by PGI2 during 10 min of incubation and then maintained for the next 5 min. Lipolysis induced by concentrations of norepinephrine which produced maximal effects was not altered by PGI2. PGI2 (10(-7)-10(-6)M) also potentiated the effect of 5 X 10(-4)M theophylline on glycerol release, but antagonized the stimulation induced by a maximally effective concentration of the methylxanthine (2 X 10(-3)M). Incubation of the cells with norepinephrine in the presence of 2 X 10(-4) or 5 X 10(-4)M theophylline caused a loss of the potentiating effect of PGI2 on norepinephrine-induced lipolysis. In the presence of 10(-3)M theophylline, the lipolytic action of norepinephrine was inhibited by PGI2. In fat cells incubated with adenosine deaminase (0.5 U/ml), 2.5 X 10(-7)M PGI2 did not alter the response to 5 X 10(-4)M theophylline and inhibited the effect of norepinephrine both in the absence and in the presence of theophylline. The present results show that, under appropriate experimental conditions, PGI2 may act as a lipolytic agent in isolated fat cells and that some kind of interaction exists between stimulation of methylxanthine-sensitive adenosine receptors and stimulation of PGI2 receptors.
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PMID:Prostacyclin and lipolysis in rat fat cells. 639 92

S-Adenosyl-L-homocysteine hydrolase has been purified to apparent homogeneity from rat liver by means of affinity chromatography on 8-(3-aminopropylamino)adenosine linked to Sepharose. The purified enzyme was free from adenosine kinase and adenosine deaminase activities and was homogeneous on SDS/polyacrylamide-gel electrophoresis which gave a subunit mol.wt. of 47 000. The native enzyme showed some microheterogeneity on polyacrylamide-gel electrophoresis under increased-resolution conditions but was homogeneous on isoelectric focusing (pI 5.6). The molecular weight of the native enzyme was about 220 000 as judged by pore-gradient electrophoresis. The native enzyme bound adenosine tightly and showed Km values of 0.6 microM, 0.9 microM and 60 microM for adenosine, S-adenosyl-L-homocysteine and L-homocysteine respectively. The enzyme was rapidly inactivated when incubated in the presence of adenosine, S-adenosyl-L-homocysteine or several adenosine derivatives or analogues. Inactivation took place both at 0 and 37 degrees C. Freezing in the absence of glycerol resulted in the appearance of dissociation products of the oligomeric protein. Multimer formation was observed at low thiol concentrations.
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PMID:Affinity-chromatographic purification of S-adenosyl-L-homocysteine hydrolase. Some properties of the enzyme from rat liver. 730 45

Young adult male rats were treated with 4 mg dehydroepiandrosterone (DHEA)/100-g diet for 4 wk or were fed the same purified diet unadulterated (51 carbohydrate:20 fat: 23.5 protein; wt/wt). After 1 wk body weight and fat mass of the DHEA-fed rats were significantly less than the controls. By the end of week 3, fat-free mass of the DHEA rats was less than the controls. Neither food intake nor resting metabolism, measured by indirect calorimetry, was different between groups. Isolated epididymal adipocytes of DHEA rats were significantly smaller and isoproterenol (x 10(7) M) stimulation of glycerol release was 53% greater (P < 0.01) than the controls. Basal rate of glycerol release increased significantly for both groups in response to the adenosine inhibitor adenosine deaminase; there were no significant interaction effects. Inhibition of lipolysis by the adenosine analogue phenylisopropyladenosine was similar between groups. Findings support the hypothesis that DHEA reduces adiposity directly by increased lipolysis, but the mechanism of action does not involve a change in the antilipolytic function of adenosine.
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PMID:Increased lipolysis to beta-adrenergic stimulation after dehydroepiandrosterone treatment in rats. 761 11

White and brown rat adipocytes have been permeabilised by repeated exposure of the cells in suspension to high voltage electrical discharges. The resulting preparations were permeable to low molecular weight materials, e.g., cyclic AMP, propidium iodide, and were stable in suspension with little evidence of rapid resealing, or of gross damage to the cell membrane. Leakage of lactate dehydrogenase was not markedly enhanced except at voltages in excess of 2 kV cm-1 for brown adipocytes. Exogenously-added cyclic AMP stimulated lipolysis (measured as glycerol release) in the electropermeabilised adipocytes far more effectively than in intact adipocytes. In brown, but not in white, adipocytes this effect was enhanced by addition of millimolar ATP. The EC50 for stimulation of glycerol release by cyclic AMP was 0.2 microM in electropermeabilised brown adipocytes, and 2 microM and 40 microM in electropermeabilised white adipocytes obtained from weanling and adult rats respectively. The effect of cyclic AMP on lipolysis was enhanced by addition of an inhibitor of cyclic AMP phosphodiesterases and was reduced by addition of 5'-AMP, adenosine or inosine (in brown adipocytes). Addition of adenosine deaminase caused a small, but significant, enhancement of cyclic AMP-driven lipolysis. Catecholamine-driven lipolysis was observed in electropermeabilised brown and white adipocytes, especially in the presence of GTP. Adrenaline-, and to a lesser extent cyclic AMP-, driven lipolysis in electropermeabilised white adipocytes was inhibited by insulin. This effect of insulin was not enhanced by addition of GTP or of a metabolically stable GTP analogue. The results obtained establish the electropermeabilised preparation as suitable for analysis of signal transduction pathways in white and brown adipocytes.
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PMID:Studies on signal transduction mechanisms for adrenaline-driven lipolysis in white and brown adipocytes. 816 54

We studied the effect of variable isolated fat cell concentrations (from 0.17 to 1.25 x 10(6) cells/ml) on rate and pattern of basal and insulin-stimulated glucose metabolism by rat epididymal fat cells. Cell concentration did not affect total glucose utilization, but high cell concentrations increased the absolute and relative conversion of glucose to CO2 and glyceride-fatty acids by two- to threefold and decreased the conversion to lactate, pyruvate, and glyceride-glycerol when compared with values observed at low cell concentration. When effects of adenosine deaminase (ADA) and N-6(2-phenylisopropyl)adenosine (PIA) were examined, addition of ADA to incubated cells produced no significant changes in the rate or pattern of adipocyte glucose metabolism; PIA had a slight and uniform effect on the conversion of glucose to its metabolic products and minimal effect on insulin-stimulated glucose metabolism. Medium free fatty acid concentration did not change during the incubation at various cell density, but intracellular free fatty acids were found to be inversely related to fat cell density in the medium. Thus a variable fat cell density influences the pattern of adipocyte glucose metabolism in vitro. This effect may be due to variable rates of lipolysis and resulting changes in intracellular fatty acid concentration rather than to adenosine per se. This work has practical implications in the need to define cell density when carrying out in vitro measurements of adipocyte glucose conversion to products.
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PMID:Effects of cell density on in vitro glucose metabolism by isolated adipocytes. 846 Jun 83

The possible modification of the in vitro lipolytic action of rat growth hormone (rGH) or a mixed beta-adrenergic agonist (metaproterenol) on rat adipose tissue after a previous acute treatment with these compounds was assessed by measuring glycerol release from adipocytes. The involvement of adenosine deaminase (ADA) and dexamethasone, was also considered. The results showed that the previous acute treatment with rGH or the beta-adrenergic agonist did not alter the in vitro rGH or metaproterenol lipolytic response. The presence of ADA at a non-lipolytic concentration per se (0.02 U/ml) potentiated the lipolytic response of both compounds. Also, the addition of non-lipolytic concentrations of dexamethasone (0.5 microM) or beta-adrenergic agonist (10(-7)M) to the incubation medium potentiated the rGH lipolytic response, while the metaproterenol-induced glycerol release was not affected by the simultaneous addition of a rGH concentration (2 x 10(-7) M) which had no lipolytic effect per se.
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PMID:Analysis of the interactions between growth hormone and metaproterenol on lipid mobilization. 860 92

To examine a possible metabolic regulatory role for adenosine, infusions of adenosine and adenosine deaminase were given to 11 near-term fetal sheep during the simulation of birth in utero. Fetal arterial blood gases, the concentration of a number of metabolites, insulin, and whole body O2 consumption (VO2) were measured. After intrauterine ventilation and cord occlusion, fetal/neonatal VO2, measured by closed-circuit respirometry, averaged 11.0 +/- 1.1 (SE) ml (STPD).min-1.kg fetal wt-1 and plasma adenosine concentration ([Ado]) was 1.29 +/- 0.21 microM. Infusion of adenosine (1.5 mumol.min-1.kg-1) during the next 30-min interval increased [Ado] to 1.57 +/- 0.28 microM (not significant) and decreased VO2 to 7.7 +/- 0.5 ml.min-1.kg-1 (P < 0.05). The infusion reduced systolic blood pressure by 19% (P < 0.01) and diastolic blood pressure by 25% (P < 0.01) and increased heart rate by 19% (P < 0.01). At the highest rate of adenosine infusion studied (6 mumol.min-1.kg-1), [Ado] increased to 4.27 +/- 0.46 microM (P < 0.001) and VO2 did not measurably decline further, although there were further decreases in blood pressure and increases in heart rate. After administration of adenosine deaminase, [Ado] decreased to 0.58 +/- 0.13 microM (P < 0.05), whereas VO2 increased to 11.2 +/- 0.8 ml.min-1.kg-1 (P < 0.05); blood pressure and heart rate returned to basal levels. The dependence of VO2 on [Ado] is described by the relationship VO2 = 6.14 + 4.89 exp(-0.45[Ado]) (n = 144; r = 0.34; P < 0.001). Throughout the experiment, arterial O2 content and plasma glucose, lactate, glycerol, and fatty acid concentrations were normal or elevated, and, therefore, O2 lack and substrate deficiency were unlikely to have caused the reduction in VO2. We conclude that plasma adenosine may act as a messenger of energy status for the ovine fetus/neonate and may contribute thereby to a maintenance of a balance between O2 supply and O2 demand.
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PMID:Exogenous infusion of adenosine depresses whole body O2 use in fetal/neonatal sheep. 887 16

Because one manifestation of diabetes is an enhancement of the lipolytic process, we evaluated the antilipolytic effects of adenosine A1 agonists in vitro and in vivo in streptozotocin (STZ)-treated diabetic rats. In vitro, we examined the responses to norepinephrine (NE) and adenosine deaminase (ADA), as well as several adenosine A1 agonists, in isolated adipocytes from normal and diabetic rats. Both NE and ADA caused dose-dependent stimulation of lipolysis, elevating glycerol release twofold to threefold over baseline. The sensitivity to both NE and ADA was significantly enhanced in adipocytes from STZ-treated as compared with normal rats. N-5'-ethyl-N(6)(cyclopentyl) adenosine-5'-uronamide (RG14202) was by far the most potent A agonist in inhibiting NE-stimulated lipolysis [50% effective concentration (EC50): 0.014 +/- 0.0008 nM), approximately 1 and 2 log units more potent than N(6)-cyclopentyladenosine (CPA) and N(6)-cyclohexyl-2'-O-methyladenosine (SDZ WAG 994), respectively. In vivo we established a model for evaluating the therapeutic utility of adenosine A1 agonists, emphasizing duration of action. In STZ rats instrumented with telemetry transmitters, the metabolic effects of CPA, RG14202, and SDZ WAG 994 were assessed 6 h after oral administration. Under those conditions, RG14202 and SDZ WAG 994, but not CPA, significantly reduced triglycerides (TRIs) and TRI/free fatty acids (FFAs), respectively. However, all three A1 agonists dose-dependently reduced mean arterial pressure (MAP) and heart rate (HR) concurrently. Thus adenosine A1 agonists can inhibit lipolysis in vitro and in vivo; however, oral administration produces long-lasting beneficial metabolic effects only at doses that also produce a significant bradycardia.
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PMID:Cardiovascular and metabolic effects of adenosine A1-receptor agonists in streptozotocin-treated rats. 912 82

Progesterone rapidly inhibits glucose oxidation of isolated rat adipocytes. Because this inhibition is triggered by endogenous adenosine, the present study was designed to examine the effect of the steroid on cyclic adenosine monophosphate (cAMP) accumulation, its relation to lipolysis, and the possible participation of adenosine. The results strongly indicate that physiological concentrations of progesterone increase the release of adenosine by isolated adipocytes, with maximal release at the end of a 20-minute incubation. Progesterone decreased both cAMP levels and lipolysis in quiescent adipocytes or in adipocytes stimulated by isoproterenol. The increase of endogenous adenosine may explain the decline of cAMP and glycerol levels observed with progesterone. The effects of the steroid on lipolysis disappeared when adenosine was hydrolyzed by adenosine deaminase (ADA). On the other hand, in the absence of endogenous adenosine, the effect of progesterone on the cAMP level was decreased only in isoproterenol-stimulated cells. The inhibitory effects of progesterone on cAMP and glycerol production seem not to be related directly to the adenosine A1 receptor, for selective A1 receptor antagonists (8-cyclopentyl-1,3-dipropylxanthine [DPCPX] and CP 68,247) did not counteract these effects. However, mechanisms mediated by guanyl nucleotide binding proteins cannot be excluded. The decrease of cAMP and of lipolysis may be related to a stimulation of phosphodiesterases (PDEs). When PDEs I [Ca(2+)-calmodulin-regulated PDE family) were blocked by a selective inhibitor (CP 41,757), the progesterone inhibitory effect persisted, suggesting that PDEs I are not regulated by the steroid. On the other hand, the progesterone effect on cAMP accumulation but not on lipolysis disappeared in the presence of a selective inhibitor of the PDE IV family (cAMP-dependent-specific family). Ro 20.1724. When the specific inhibitor of PDE I or PDE IV was combined with ADA, the progesterone effect on cAMP disappeared. Taken together, these results suggest that the progesterone inhibitory action on cAMP levels was not mediated through A1 receptors or through activation of PDE I, but may be related to PDE IV activities. The progesterone effect on lipolysis seemed not to be directly related to changes in cAMP levels; an effect on PDE III activities in relation with the increase of adenosine release cannot be excluded.
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PMID:Acute effects of progesterone on glucose metabolism in rat adipocytes: are they modulated by endogenous adenosine? 918 92

The aim of this study was to investigate and clarify the role of prostaglandins (PG) on fat cell lipolysis in female rats. Incubations with adenosine deaminase (ADA) were used for the deamination of endogenous adenosine and increased basal (155%) and isoproterenol (10(-9) M) (348%) stimulation of glycerol release from adipocytes. Indomethacin and aspirin increased the effects of ADA while indomethacin further increased isoproterenol (with ADA) stimulation of lipolysis (p < or = 0.05). Exogenous PGE2 and PGI2 inhibited the isoproterenol and ADA stimulation of fat cell lipolysis (p < or = 0.05). The expected stimulatory effect of high concentrations of PGE2 and of low concentrations of PGI2 was not observed in the presence of ADA. Dose-response curves revealed that the inhibitory effects of PGs were reached at lower concentrations for PGE2 than for PGI2 (p < or = 0.05). In conclusion, this study showed that endogenous and exogenous PGs of adipose tissue only express an antilipolytic action on fat cell lipolysis. This effect appears to be highly significant when the beta-adrenergic pathway is stimulated. Our results also stress the need to control the antilipolytic effects of adenosine to study the regulation of fat cell lipolysis by PGs.
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PMID:The lack of bimodality in the effects of endogenous and exogenous prostaglandins on fat cell lipolysis in rats. 967 20


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