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 fat cells isolated from the parametrial adipose tissue of rats, the addition of purified adenosine deaminase increased lipolysis and cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation. Adenosine deaminase markedly potentiated cyclic AMP accumulation due to norepinephrine. The increase in cyclic AMP due to adenosine deaminase was as rapid as that of theophylline with near maximal effects seen after only a 20-sec incubation. The increases in cyclic AMP due to crystalline adenosine deaminase from intestinal mucosa were seen at concentrations as low as 0.05 mug per ml. Further purification of the crystalline enzyme preparation by Sephadex G-100 chromatography increased both adenosine deaminase activity and cyclic AMP accumulation by fat cells. The effects of adenosine deaminase on fat cell metabolism were reversed by the addition of low concentrations of N6-(phenylisopropyl)adenosine, an analog of adenosine which is not deaminated. The effects of adenosine deaminase on cyclic AMP accumulation were blocked by coformycin which is a potent inhibitor of the enzyme. These findings suggest that deamination of adenosine is responsible for the observed effects of adenosine deaminase preparations. Protein kinase activity of fat cell homogenates was unaffected by adenosine or N6-(phenylisopropyl)adenosine. Norepinephrine-activated adenylate cyclase activity of fat cell ghosts was not inhibited by N6-(phenylisopropyl)adenosine. Adenosine deaminase did not alter basal or norepinephrine-activated adenylate cyclase activity. Cyclic AMP phosphodiesterase activity of fat cell ghosts was also unaffected by adenosine deaminase. Basal and insulin-stimulated glucose oxidation were little affected by adenosine deaminase. However, the addition of adenosine deaminase to fat cells incubated with 1.5 muM norepinephrine abolished the antilipolytic action of insulin and markedly reduced the increase in glucose oxidation due to insulin. These effects were reversed by N6-(phenylisopropyl)adenosine. Phenylisopropyl adenosine did not affect insulin action during a 1-hour incubation. If fat cells were incubated for 2 hours with phenylisopropyl adenosine prior to the addition of insulin for 1 hour there was a marked potentiation of insulin action. The potentiation of insulin action by prior incubation with phenylisopropyl adenosine was not unique as prostaglandin E1, and nicotinic acid had similar effects.
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PMID:Effects of adenosine deaminase on cyclic adenosine monophosphate accumulation, lipolysis, and glucose metabolism of fat cells. 16 37

The rates of glycerol release in adipocytes isolated from nine identified adipose depots of sedentary or exercised guinea-pigs were measured in the presence of adenosine deaminase and 10(-9) to 10(-5) M noradrenaline and/or 1-1000 muunit/ml of bovine insulin. Twenty minutes of exercise increased the basal noradrenaline-stimulated rates of lipolysis in all depots, but these effects, and their interactions with in vitro application of the neurotransmitter differed between depots, showing that the long-lasting effects of exercise and the response to acute application of NA involve different mechanisms that may occur separately or together in different adipose depots. In general, large depots had the highest resting rates of lipolysis and the lowest responses to both noradrenaline and insulin, and lipolysis was only slightly different from the basal rate in adipocytes incubated with mixtures of the two agents. The two small intermuscular depots had the lowest unstimulated rates of lipolysis, but the fastest change and greatest maximum response to both agents. Noradrenaline-stimulated lipolysis was most effectively inhibited by small quantities of insulin in these depots. Different combinations of these properties were demonstrated in two smaller superficial depots, the mesenteric and omental depot, and in the cardiac depots. The data demonstrate the physiological inhomogeneity of both 'subcutaneous' and 'intra-abdominal' depots, and are consistent with the hypothesis that intermuscular adipose tissue interacts locally with adjacent muscle. Noradrenaline-stimulated lipolysis was more effectively inhibited by 100 muunit/ml insulin in adipocytes from the mesenteric and omental depot in those from any other site. A possible role for this property in the enlargement of this depot in hyperinsulinaemia in humans is proposed.
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PMID:The effects of noradrenaline and insulin on lipolysis in adipocytes isolated from nine different adipose depots of guinea-pigs. 183 17

The effects of adenosine and of some products of its metabolic degradation on lipolysis were studied in rat fat cells isolated from epididymal adipose tissue. Basal glycerol release was not affected by adenosine and by uric acid, but it was significantly increased by inosine (1-100 microM) and by hypoxanthine (10-100 microM). Adenosine was more effective than inosine in antagonizing the lipolytic response of fat cells to theophylline. Also hypoxanthine and uric acid exerted a very potent, noncompetitive antagonism towards theophylline. Norepinephrine-induced lipolysis was inhibited by adenosine, hypoxanthine and uric acid approximately to the same extent, while inosine was ineffective at this level. Adenosine deaminase (0.5 U/ml) increased basal as well as theophylline- and norepinephrine-induced lipolysis. Moreover, adenosine deaminase enhanced the lipolytic rate in cells incubated with low (0.1, 1 microM) and, to a lesser extent, with high (10, 100 microM) inosine concentrations. These results suggest that inosine is the adenosine metabolite that may accumulate in the incubation medium following fat cell treatment with adenosine deaminase, thus contributing to the stimulatory effects of this enzyme on lipolysis.
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PMID:A reexamination of the effects induced by adenosine and its degradation products on rat fat cell lipolysis. 340 Dec 55

1. Plasma and adipose tissue purine nucleosides were assayed by reversed phase high-performance liquid chromatography after purification of the samples on phenylboronate affinity gel. 2. The adenosine content of unstimulated subcutaneous adipose tissue was close to 1 n-mole/g. The concentrations of adenosine and inosine in canine arterial plasma were 0.26 +/- 0.03 and 0.16 +/- 0.03 microM, respectively. In venous plasma from the canine subcutaneous adipose tissue the corresponding values were 0.32 +/- 0.04 and 0.28 +/- 0.06 microM under basal conditions. The arterio-venous concentration difference of adenosine was linearly dependent upon the arterial adenosine concentration. At arterial concentrations below 0.3 microM there was a net production of adenosine; above 0.3 microM there was a net extraction of approximately 77% of the adenosine. Adenosine was extensively eliminated in blood. The major part of this elimination could be accounted for by metabolism to inosine, hypoxanthine and uric acid. 3. Following sympathetic nerve stimulation (4 Hz for 20 min) the rate of adenosine outflow from adipose tissue increased from 0.33 +/- 0.22 to a peak value of 1.2 +/- 0.26 n-mole/min. This corresponds to a net release of 8.7 +/- 3.0 n-mole/100 g tissue. Inosine outflow rose from 0.64 +/- 0.37 to 5.3 +/- 1.4 n-mole/min, corresponding to a net release of 24.6 4/- 8.7 n-mole/100 g. Nerve stimulation also increased the release of [3H]purines from [3H]adenine pre-labelled adipose tissue. The fractional release increased 15-fold after stimulation. The radioactivity was mainly in the form of hypoxanthine, inosine and uric acid while adenosine was a minor component. When metabolism in blood was inhibited by dipyridamole and an adenosine deaminase inhibitor nerve-stimulation-induced release of [3H]purines was mainly in the form of adenosine. 4. Noradrenaline injection also induced a release of radioactive purines and of inosine. On the other hand, the outflow of endogenous adenosine was very small. 5. The present results demonstrate that under basal conditions adenosine is present in arterial and venous canine plasma. The free extracellular tissue level may be similar to the basal arterial adenosine concentration. Sympathetic nerve stimulation and noradrenaline induces a marked release of adenosine which is rapidly metabolized in the tissue and blood stream to inosine, hypoxanthine and uric acid. In adipose tissue the levels of adenosine reached after adrenergic stimulation appear high enough to be of physiological relevance.
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PMID:The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline. 727 25

Adenine dinucleotides such as beta-NAD, alpha-NAD, NADP, 3-aminopyridine adenine dinucleotide, flavin adenine dinucleotide, 3',5'-and 2',5'-adenylyladenosine mimicked the inhibitory effects of adenosine and adenine nucleotides on electrically evoked contractions of the rat and mouse isolated superfused vas deferens. The inhibitory effects were blocked by theophylline or adenosine deaminase, unaffected by the nucleotidase inhibitor alpha, beta-methylene ADP and enhanced by inhibition of adenosine deaminase. The inhibitory effects were associated with a release of purines from the vasa after preloading with [3H]adenosine. It is suggested that these compounds activate a receptor, causing the release of adenosine which is largely responsible for the inhibitions. Diadenosine pyrophosphate and triphosphate caused only depression of the vas twitch, whereas the pentaphosphate and hexaphosphate derivatives caused contraction, followed by inhibition at higher concentrations. These inhibitions were only partly reduced by theophylline or deaminase, but both contractile and inhibitory effects were enhanced by alpha, beta-methylene ADP. Noradrenaline contractions were also reduced by the higher polyphosphates. It is suggested that there may be a receptor for these dinucleotides, located at least in part postjunctionally. The pentaphosphate and hexaphosphate compounds mimicked the effects of nerve stimulation on the guinea-pig bladder, being substantially more potent than beta, gamma-methylene-ATP, and on the taenia caeci, where contraction or relaxation could be produced depending on resting tone.
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PMID:Actions of adenine dinucleotides on the vas deferens, guinea-pig taenia caeci and bladder. 731 4

1. The effects of analogues of adenosine and ATP on noradrenaline release elicited by electrical stimulation (5 Hz, 2700 pulses) were studied in superfused preparations of rat tail artery. The effects of purinoceptor antagonists, of adenosine deaminase and of adenosine uptake blockade were also examined. Noradrenaline was measured by h.p.l.c. electrochemical detection. 2. The A1-adenosine receptor agonist, N6-cyclopentyladenosine (CPA; 0.1-100 nM) reduced, whereas the A2A-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30 nM) increased evoked noradrenaline overflow. These effects were antagonized by the A1-adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 20 nM) and the A2-adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 100 nM), respectively. The P2Y-purinoceptor agonist, 2-methylthio-ATP (1-100 microM) reduced noradrenaline overflow, an effect prevented by the P2-purinoceptor antagonist, cibacron blue 3GA (100 microM) and suramin (100 microM). 3. Adenosine deaminase (2 u ml-1), DMPX (100 nM) and inhibition of adenosine uptake with S-(p-nitrobenzyl)-6-thioinosine (NBTI; 50 nM) decreased evoked noradrenaline overflow. DPCPX alone did not change noradrenaline overflow but prevented the inhibition caused by NBTI. The P2Y-purinoceptor antagonist, cibacron blue 3GA (100 microM) increased evoked noradrenaline overflow as did suramin, a non-selective P2-antagonist. 4. It is concluded that, in rat tail artery, inhibitory (A1 and P2Y) and facilitatory (A2A) purinoceptors are present and modulate noradrenaline release evoked by electrical stimulation. Endogenous purines tonically modulate noradrenaline release through activation of inhibitory P2Y and facilitatory A2A purinoceptors, whereas a tonic activation of inhibitory A1 purinoceptors seems to be prevented by adenosine uptake.
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PMID:Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors. 882 57

A simple and sensitive method for direct and continuous monitoring of free fatty acid (FFA) release, by measuring the pH-sensitive change in relative fluorescence intensity of seminaphthofluorescein (SNAFL-1) is described. The method was designed to use a small number of adipocytes isolated from fat pads of rats and biopsy specimens of horses for the detection of decreasing pH in fat cell suspensions caused by released FFA into the incubation medium. Species specific differences of lipolysis were demonstrated when adipocytes of rats and horses are incubated with stimulators or inhibitors of lipolysis. Norepinephrine (NE) stimulated lipolysis in fat cells of rats whereas adipocytes of horses showed a measurable release of FFA when concomitantly incubated with NE and adenosine deaminase (ADA) or NE and 8-Phenyltheophylline (8-PT), respectively). The incubation of equine fat cells with NE and ADA did not influence the antilipolytic response to insulin. The method described enables micro-scaled in vitro studies on lipolytic activity.
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PMID:Studies on equine lipid metabolism. 1. A fluorometric method for the measurement of lipolytic activity in isolated adipocytes of rats and horses. 992 46

The enzymatic fundamentals of lipid metabolism of equine have not been thoroughly investigated at this point in time. It is still unclear why ponies in contrast to horses may become hyperlipaemic when coming negative energy balance. In this study, the activities of the triglyceride-cleaving key enzymes of ponies are large bred horses were investigated in order to obtain insight into the aetiology of the syndrome. The objective of the study was to measure the activities of hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in ponies and horses in ex vivo in vitro assays. Norepinephrine (NE) stimulated pony adipocytes to release FFA in a linear fashion (4.57 +/- 2.09 nmol FFA.10(5) cells-1.min-1). This was not observed in horses. Lipolysis was significantly higher in fat cells of ponies than in horses when adenosine deaminase (ADA) and NE were added (12.71 +/- 3.12 vs. 1.96 +/- 1.22 nmol FFA.10(5) cells-1.min-1). Relative inhibition of lipolysis by the action of insulin was comparable in adipocytes of horses and ponies. However, absolute FFA release in pony fat cells was as high as the maximal NE and ADA stimulated lipolysis in horse adipocytes. Postheparin plasma lipase activities in ponies and horses did not differ between the sub-species. This finding was supported by the results obtained from measurement of LPL activity in adipose and muscle tissue showing only a tendency of increased activities in pony explants when compared to horse tissue incubations. This study further supports the hypothesis that differences in regulation of TG release from fat stores rather than clearance of TG from plasma is causative for the development of hyperlipaemia in ponies. Abbreviations used: ADA, adenosine deaminase; BW, body weight; FFA, free fatty acid; HSL, hormone-sensitive lipase; HTGL, hepatic triglyceride lipase; LPL, lipoprotein lipase; NE, norepinephrine; SDS, sodium dodecyl sulfate; TG, triglyceride; VLDL, very low density lipoprotein.
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PMID:Studies on equine lipid metabolism. 2. Lipolytic activities of plasma and tissue lipases in large horses and ponies. 1008 66

A highly sensitive fluorometric assay technique was adopted in order to examine the adenylate cyclase activity in the minute right ventricular endomyocardial biopsy samples from patients with chronic congestive heart failure (n = 10). Norepinephrine (10(-4) M) and adenosine (10(-3) M) were incubated for 30 min with 10 microl of membrane preparation (1-2 mg protein/mg) to analyze the extent of the receptor-coupled adenylate cyclase activity. Forskolin (10(-4) M) stimulation was used to estimate the maximum adenylate cyclase activity (pmol/mg protein/min, mean +/- SE). The new microanalytical cyclic AMP assay involves four steps: enzymatic destruction of noncyclic adenine nucleotides and phosphorylated metabolites, conversion of cyclic AMP to ATP, amplification of ATP by enzymatic cycling, and fluorometric measurement of NADPH, which is generated in proportion to initial cyclic AMP levels. Basal and forskolin-stimulated maximum adenylate cyclase activities were 75 +/- 8 and 123 +/- 15, respectively. Norepinephrine increased the adenylate cyclase activity to 107 +/- 14, while adenosine tended to decrease it to 65 +/- 7. In addition, elimination of adenosine by adenosine deaminase (10 U/ml) slightly increased the adenylate cyclase activity to 82 +/- 9. These results indicate that the adenylate cyclase activity can be measured in minute endomyocardial biopsy samples. Use of this new approach shows promise of becoming a new and potentially important way to predict the efficacy of pharmacological treatment.
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PMID:Measurement of adenylate cyclase activity in the right ventricular endomyocardial biopsy samples from patients with chronic congestive heart failure. 1068 13

The synthesis of noradrenaline was measured, using high-performance liquid chromatography with electrochemical detection, in synaptosomal fractions prepared from rat hippocampus. Noradrenaline synthesis is depressed by adenosine deaminase and the adenosine antagonist, 8-phenyltheophylline and stimulated by the adenosine agonist, 2-chloroadenosine. ?-Adrenoceptor stimulation also increases synthesis. The adenosine receptors and ?-adrenoceptors do not interact. Both receptor-mediated effects are distinct from, and additive with, the acceleration of synthesis by potassium-depolarisation. The results are compatible with an adenosine-receptor and ?-adrenoceptor stimulation of adenylate cyclase, leading to a cyclic AMP-mediated activation of tyrosine hydroxylase.
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PMID:Adenosine receptor and beta-adrenoceptor stimulation increases noradrenaline synthesis in hippocampal synaptosomes. 2049 43


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