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)

Gelfiltered platelets (GFP) in calcium free Tyrode solution containing albumin, glucose and adenosine deaminase were preincubated with 1 micronM 14C-ADP or 0.15 M NaCl (control) at 37 degrees C. The breakdown of extracellular 14C-ADP was markedly inhibited in this medium. No aggregation took place without fibrinogen, but the platelets underwent a disc to sphere transformation with development of refactoriness towards ADP. Presence of 2 mM CaCl2 in the incubation medium did not prevent refractoriness as reported earlier with washed rabbit platelets. When the ADP degrading enzyme, apyrase, was added at 30 min of incubation a partial recovery of the aggregability was observed. Electron microscopic studies showed that the partial restoration of the aggregation response, due to ADP degradation by apyrase, was accompanied by a return of discoidal morphology of the platelets. The ultrastructural studies showed further that spherical form with large number of pseudopods is not by itself a necessary or sufficient indication of platelets in a refractory state. However, the results indicated that spherical platelets are more vulnerable to external factors. It was concluded that refractoriness was mainly caused by a direct effect on the platelets by ADP itself, but the studies also suggested that deteriorating, irreversible, intracellular changes may take place when platelets are in spherical shape. An artificial medium, mechanical stress, incubation at 37 degrees C are factors that probably speed up these changes.
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PMID:ADP-induced refractory state of platelets in vitro. II. Functional and ultra studies on gel filtered platelets. 85 91

Intact beating fetal mouse hearts in organ culture were deprived of oxygen and glucose for up to 4 h, resulting in loss of beating, an 80% fall in ATP, reduction of energy charge from 0.85 to 0.48, and doubling of total nucleoside concentration. Radiolabeled adenine nucleotides were degraded to hypoxanthine and inosine, which were lost from the hearts into the medium during the deprivation period. Adenosine and adenine also appeared in the medium when adenosine deaminase was inhibited. After 24 h of O2 and glucose resupply, ATP returned to 60% of control, and energy charge rose to 0.76. Labeled nucleosides and bases remaining in the heart or exogenous labeled adenine were utilized to resynthesize ATP. [14C]glycine was rapidly taken up by recovering hearts but was not used for de novo adenine nucleotide synthesis. Ability to recover ATP and spontaneous contraction appear related to residual nucleotide and nucleoside content rather than to energy charge.
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PMID:Metabolism of adenine nucleotides in the cultured fetal mouse heart. 88 70

Five enzymes concerned with the metabolism of adenine derivatives were assayed in seven regions of the rat brain. A region which included the hypothalamus had the highest AMP deaminase and adenosine deaminase activities, while its 5'-nucleotidase activities were relatively low. The enzymes named and also the uptake of [14C]adenine by incubated tissue samples were more active with hypothalamic than with neocortical tissues. On superfusion with glucose-bicarbonate saline after assimilating [14C]adenine, the hypothalamic tissues released about 0.2 per cent of their 14C content per minute. This release was increased fourfold with electrical excitation but the presence of 0.25 muM tetrodotoxin prevented most of this increase. The compounds released during superfusion and electrical stimulation were preponderantly hypoxanthine, inosine, and adenosine, with only small amounts of adenine nucleotides. The output of all these compounds increased during the period of stimulation and also the proportion of adenine nucleotides increased when stimulation was carried out in the presence of tetrodotoxin. The output of the nucleotides and adenosine increased more promptly when stimulated than did that of the other compounds named. The results are discussed in terms of the metabolic roles of the enzymes concerned. and in relation to whether the enzymes are acting on intracellular or extracellular substrates.
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PMID:The metabolism of adenine derivatives in different parts of the brain of the rat, and their release from hypothalamic preparations on excitation. 126 67

The mechanism of acetate vasorelaxation is unknown. In the rat caudal artery, acetate has a vasorelaxant effect and also increases cyclic AMP. Here we evaluate the role of adenosine, of possible glycolysis inhibition by acetate, of the lyotropic properties of acetate and other anions, and of intracellular calcium and pH. Adenosine per se did not relax the caudal artery in the range of 10(-8) to 10(-2) M. Preincubation with adenosine deaminase (ADA, 5.0 U/ml) or with 8-phenyltheophylline (8-PT, 10(-6) to 10(-4) M) increased, rather than blocked the vasorelaxant effect of acetate. Oxypurinol (10(-3) M) or the nucleoside transport inhibitor NBMPR (10(-4) M) had no effect on acetate relaxation. Whereas acetate increased tissue cyclic AMP content, 10(-3) M adenosine or 10(-6) M PIA had no effect. In strips studied under conditions of inhibited glycolysis (no glucose, with 11 mM 2-deoxyglucose, 1.0 mM pyruvate, and 0.5 mM 5-iodoacetate), acetate-induced relaxation, as well as acetate-induced cyclic AMP generation, tended to be reduced but not significantly so. Other anions relaxed vascular strips in relation to their lyotropic number, but only at higher doses, and they did not stimulate cyclic AMP formation. Acetate (10 mM) caused a transient fall in Ca2+i followed by a slight, sustained rise. A concomitant decrease in pHi was seen. DIDS, which blocks the relaxant and cyclic AMP effects of acetate, had no effect on the pHi decrease, but did decrease the rate of pHi recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The vasorelaxant effects of acetate: role of adenosine, glycolysis, lyotropism, and pHi and Cai2+. 131 76

The pharmacological profile of adenosine receptors in rat soleus muscle has been investigated by studying the effects of A1-and A2-selective adenosine receptor agonists on glucose utilization and the system A amino acid transporter under conditions where adenosine has been reported to exert a modulatory action on these insulin-sensitive processes. In the presence of adenosine deaminase and a sub-maximally effective concentration of insulin (50 microU/ml), the A1-selective agonists N6-cyclopentyladenosine and R(-)-N6-(2-phenylisopropyl)adenosine (R(-)PIA) caused concentration-dependent inhibitions of 2-deoxy[3H]glucose 6-phosphate and alpha-[14C]methylaminoisobutyric acid accumulations, but had no effect on the rate of [14C]glucose incorporation into glycogen, in incubated soleus muscle strips. These effects on glucose transport/phosphorylation and system A amino acid transport could be antagonized by 8-cyclopentyl-1,3- dipropylxanthine and 8-phenyltheophylline. The A2-selective adenosine receptor agonists CGS 21680 and 2-(phenylamino)adenosine were much less potent in their inhibition of these metabolic processes. These data support the proposal that adenosine exerts a post-receptor insulin-modulatory action in skeletal muscle and strongly suggest that this action is mediated by A1 adenosine receptors: the possible intracellular signalling mechanism(s) for this hormone-modulatory effect of adenosine are discussed.
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PMID:Characterization of the adenosine receptor modulating insulin action in rat skeletal muscle. 132 6

The (Na+,K+)-ATPase activity operative in rabbit aortic intima-media incubated with normal plasma levels of glucose and myo-inositol (70 mumol/l) is decreased when the glucose content of the medium is raised from 5 to 10 mmol/l or higher; this effect is prevented by aldose reductase inhibitors and by raising the myo-inositol content of the medium to 500 mumol/l. The decrease in (Na+,K+)-ATPase activity results from the loss of a component normally regulated (stimulated) by endogenously released adenosine through a receptor that stimulates phosphatidylinositol turnover in a discrete pool. The replenishment of this phosphatidylinositol pool selectively requires myo-inositol transport and is inhibited when increased polyol pathway activity impairs myo-inositol transport at a normal plasma level. Adenosine is a vasodilator, some endothelium-released vasodilators modulate the responses to vasoconstrictors by stimulating an increase in (Na+,K+)-ATPase activity in vascular smooth muscle. Whether adenosine mediates this effect in angiotensin II or norepinephrine-stimulated aorta was examined. Angiotensin II (100 nmol/l) and norepinephrine (1 mumol/l) evoked marked increases in (Na+,K+)-ATPase activity in aortic intima-media incubated with 5 mmol/l glucose and 70 mumol/l myo-inositol, which were inhibited when adenosine deaminase was added or the medium myo-inositol omitted to inhibit myo-inositol transport. Raising the medium glucose to 30 mmol/l inhibited the angiotensin II and norepinephrine-evoked increases in (Na+,K+)-ATPase activity, and this was prevented when tolrestat (10 mumol/l) was added or the myo-inositol content of the medium was raised from 70 to 500 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms in rabbit aorta for hyperglycaemia-induced alterations in angiotensin II and norepinephrine effects. 132 61

We have studied the effects of insulin, adenosine and 12-O-tetradecanoylphorbol-13-acetate (TPA) on glucose metabolism of the retinal pigmented epithelial (RPE) cells in vitro. Insulin stimulates glucose transport, glucose oxidation and lipogenesis in RPE cells. TPA at low concentrations of insulin increases the rates of glucose transport and glucose oxidation. Depletion of adenosine in RPE cells by adenosine deaminase increases the rate of both glucose transport and 14CO2 formation and improves insulin-sensitivity of both processes. The effects of TPA on RPE cells cannot be explained by the activation of protein kinase C. An alternative possibility is that the effects of TPA on insulin-stimulated glucose disposal in RPE cells is mediated by a change in adenosine concentration and/or the affinity/number of its receptors.
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PMID:Effects of insulin and a tumour promoter, TPA, on glucose transport and metabolism in retinal pigmented epithelium in vitro. 141 11

It has been established that adenosine, its agonists, or antagonists can cause dramatic changes in insulin sensitivity in isolated soleus muscle and, moreover, can modify changes in sensitivity caused by pathophysiological conditions. Addition of adenosine deaminase to the incubation medium, which is known to lower the concentration of adenosine, increases the sensitivity of glycolysis to insulin. Addition of an adenosine-receptor agonist decreases sensitivity by about 10-fold, whereas addition of an adenosine-receptor antagonist increases sensitivity by about 10-fold. The latter totally removes the resistance of glucose utilization to insulin in the isolated soleus muscle obtained from either the genetically obese rat or from the rat fed a high sucrose diet. These findings strongly support the view that changes in insulin sensitivity in muscle can be brought about either by acute changes in the local concentration of adenosine or in the affinity or number of receptors for adenosine in muscle. However, in many of the conditions investigated, in which insulin sensitivity in muscle is changed, there was no correlation between the change in the adenosine content of the muscle and altered insulin sensitivity. It has also been shown that prostaglandin E1 can increase dramatically the sensitivity of glycolysis to insulin and that this is a specific effect of prostaglandins of the E series. It is not produced by prostacyclins, thromboxanes, or leukotrienes. It is unclear if there is a relationship between the effects of adenosine and prostaglandins. Chronic elevation of catecholamines may increase the sensitivity of glucose utilization to insulin and also increase the rate of thermogenesis by substrate cycling.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recent developments in metabolism that impinge on research into the nature and treatment of diabetes mellitus. 146 6

The effects of burn injury and sepsis on intracellular lymphocyte metabolism were evaluated using a rat model. Adult Lewis rats were subjected to a sham burn, a 30% full-thickness burn, or a 30% full-thickness burn which was infected with Pseudomonas aeruginosa. One week later the animals were sacrificed, and the splenic lymphocytes were harvested and cultured for 24 hr with mitogen stimulation. Lymphocytes from the burned-infected rats were found to utilize more glucose and certain amino acids than did lymphocytes obtained from the other two groups. Lymphocytes obtained from the burned-infected group had lower levels of the immunologically important enzyme, adenosine deaminase, than did the lymphocytes obtained from the other two groups. In summary, sepsis appears to alter a number of intracellular lymphocyte metabolic processes. These alterations may be found to be predictive of early sepsis.
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PMID:Alterations in intracellular lymphocyte metabolism induced by infection and injury. 152 55

Previous studies have demonstrated that human malignancies can synthesize large amounts of thromboxane. It has also been reported that thromboxane can significantly alter multiple components of physiologic and immunologic function. We investigated the effect of elevated levels of thromboxane on host response to tumor using multiple rat models, and the long acting thromboxane analogue U-46619. Administration of the thromboxane analogue was not found to significantly alter the growth of primary tumors or peritoneal metastases. The analogue was found to significantly decrease mean survival time with a pulmonary metastases model. The thromboxane analogue failed to alter macrophage cytotoxicity, lymphocyte cytotoxicity, T lymphocyte subset numbers, or lymphocyte blastogenic response. Administration of the thromboxane analogue decreased the rate of lymphocyte metabolism of glucose and decreased lymphocyte intracellular adenosine deaminase activity. In conclusion, elevated thromboxane levels do not appear to alter primary tumor growth or host immune function, but do decrease resistance to pulmonary metastases.
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PMID:The effect of elevated levels of thromboxane on host response to tumor. 154 78


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