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)

1. Rats (4 weeks old) were made hypothyroid by treatment with propylthiouracil and a low-iodine diet for a further period of 4 weeks. Synaptosomal membranes, myelin and 105,000 g soluble fractions were obtained from six regions of the brain. 2. Hypothyroidism resulted in 2-5-fold increases in membrane-bound 5'-nucleotidase activity in synaptosomal fractions obtained from cerebellum, cortex, striatum and hippocampus. By contrast, myelin 5'-nucleotidase activity was slightly increased only in the medulla oblongata. 3. Hypothyroidism did not change adenosine deaminase activity, but decreased adenosine kinase activity by approx. 40% in soluble fractions obtained from cerebellum, hippocampus, striatum and hypothalamus. 4. It is suggested that these changes in hypothyroidism, in particular the increases in 5'-nucleotidase activity, could enhance the neuromodulatory effect of adenosine to decrease neurotransmitter release.
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PMID:Changes in the activities of adenosine-metabolizing enzymes in six regions of the rat brain on chemical induction of hypothyroidism. 254 78

The value of ascitic fluid adenosine deaminase activity in distinguishing tuberculosis from other causes of ascites was examined in a retrospective study of 41 patients with bacteriologically confirmed tuberculous peritonitis and 41 control patients, matched for age and sex, with ascites of other causes (12 alcoholic cirrhosis, 5 cryptogenic cirrhosis, 12 malignant disorders, 3 pancreatitis, and 9 miscellaneous causes). The mean ascites adenosine deaminase activity was 99.8 (SD 49.1) in tuberculous patients and 14.8 (8.4) U/l in control patients (p less than 0.0001). A cutoff of 32.3 U/l had a sensitivity of 95% and specificity of 98% in distinguishing between the two groups. In a subsequent prospective study of 64 patients with ascites, 11 were found to have tuberculosis. Of the others, 23 had cirrhosis (18 alcoholic, 5 cryptogenic), 17 malignant disorders, 3 pancreatitis, 5 cor pulmonale, 3 congestive cardiac failure, 1 systemic mastocytosis, and 1 renal failure and hypothyroidism. The mean ascites adenosine deaminase activity was 112.6 (45.0) U/l in the patients with tuberculous ascites and 16.3 (36.7) U/l (p less than 0.0001) in those with ascites of other causes. In this study, adenosine deaminase had a sensitivity of 100% and specificity of 96% in discriminating tuberculosis from other causes of ascites. These findings suggest that the ascitic fluid adenosine deaminase activity may be used to identify patients in whom the diagnosis of abdominal tuberculosis must be pursued.
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PMID:Diagnostic value of ascites adenosine deaminase in tuberculous peritonitis. 256 65

1. Adipocytes were isolated from epididymal white fat and interscapular brown fat of male rats, and activities of 5'-nucleotidase, adenosine deaminase and adenosine kinase were measured in cell extracts. 2. 5'-Nucleotidase activity in white adipocytes was increased in streptozotocin-diabetes, decreased in hypothyroidism and increased with age. That activity in brown adipocytes was unchanged in diabetes, decreased in hypothyroidism and increased with age. 5'-Nucleotidase activity was higher in white adipocytes from female rats. 3. Adenosine deaminase activity in white adipocytes was increased in diabetes, decreased in hypothyroidism and increased with age. That activity in brown adipocytes was decreased in diabetes and hypothyroidism. 4. Adenosine kinase activity in both cell types was unchanged in diabetes or hypothyroidism, but increased with age.
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PMID:Enzymes involved in adenosine metabolism in rat white and brown adipocytes. Effects of streptozotocin-diabetes, hypothyroidism, age and sex differences. 282 32

The responsiveness of lipolysis to the stimulatory agonists noradrenaline, corticotropin and glucagon and to the inhibitory agonists N6-phenylisopropyladenosine, prostaglandin E1 and nicotinic acid was investigated with rat white adipocytes incubated with a high concentration of adenosine deaminase (1 unit/ml). The cells were obtained from fed or 48 h-starved euthyroid animals or from fed or starved animals rendered hypothyroid by 4 weeks of treatment with low-iodine diet and propylthiouracil. Hypothyroidism increased sensitivity to and efficacy of all three inhibitory agonists in their opposition of noradrenaline-stimulated lipolysis. Starvation decreased sensitivity to all three inhibitory agonists when opposing basal lipolysis. Hypothyroidism decreased sensitivity to noradrenaline, glucagon and corticotropin by 37-, 4- and 4-fold respectively and decreased the maximum response to these agonists by approx. 50%, 50% and 75% respectively. Starvation reversed decreases in maximum response to these agonists in hypothyroidism. Starvation in the euthyroid state increased sensitivity to glucagon and noradrenaline, but did not alter sensitivity to corticotropin. Cells from hypothyroid rats were relatively insensitive to Bordetella pertussis toxin, which substantially increased basal lipolysis in the euthyroid state.
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PMID:Sensitivity of adipocyte lipolysis to stimulatory and inhibitory agonists in hypothyroidism and starvation. 302 50

Adenosine deaminase (1 unit/ml) potentiated the lipolytic action of noradrenaline in adipocytes isolated from brown adipose tissue of 1- and 6-week-old rats by decreasing the EC50 (concn. giving 50% of maximal effect) for noradrenaline by 3-4-fold. With cells from neonatal rabbit tissue, adenosine deaminase only had a small, non-significant, effect on the EC50 for noradrenaline. Lipolysis in rat brown adipocytes was inhibited by low concentrations of N6-phenylisopropyladenosine (PIA). Rabbit cells were far less sensitive to PIA. PIA, prostaglandin E1 and nicotinate all inhibited noradrenaline-stimulated respiration in rat brown adipocytes. Hypothyroidism diminished the maximum response of respiration and lipolysis to noradrenaline in rat cells and increased the EC50 for noradrenaline. Responsiveness of lipolysis to noradrenaline was particularly decreased in hypothyroidism and was partially restored by addition of adenosine deaminase. Lipolysis in cells from hypothyroid rats was more sensitive to the anti-lipolytic action of PIA. Bordetella pertussis toxin increased lipolysis in the presence of PIA, suggesting an involvement of the Ni guanine-nucleotide-binding protein in the control of brown-adipocyte metabolism.
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PMID:Effect of adenosine deaminase, N6-phenylisopropyladenosine and hypothyroidism on the responsiveness of rat brown adipocytes to noradrenaline. 380 Sep 44

It has been suggested that the deficient lipolytic response to catecholamines in hypothyroidism may be due to an increased sensitivity to adenosine and/or increased adenosine levels in this condition. We confirmed that the addition of adenosine deaminase enhanced the lipolytic response of hypothyroid fat cells, but the stimulation was at least as large in euthyroid cells. Adenosine analogs were more potent as antagonists of NA-induced lipolysis in hypothyroid than in euthyroid fat cells, but the difference could be explained by a decreased response to NA. Suspensions of hypothyroid cells accumulated more purine nucleosides (115 +/- 20) than did euthyroid cells (48 +/- 8 pmol/30 min/10(5) cells; p less than 0.01). This difference could not be explained by a lower rate of adenosine elimination, which occurred by three different pathways: uptake followed by phosphorylation, uptake followed by deamination and deamination by the serum albumin preparation. Under certain circumstances the latter pathway is of overwhelming importance. Fat cells from mature rats (460-480 g) behaved similarly as cells from young control rats. Thus, the changes induced by hypothyroidism was not due to a developmental change. The results are discussed in relation to earlier findings on the alterations in catecholamine responsiveness in hypothyroidism. It is concluded that an increased influence of adenosine could possibly explain some aspects of altered catecholamine responsiveness. If it does the mechanism is likely to involve an enhanced amount of adenosine rather than an increased sensitivity to adenosine.
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PMID:Accumulation and inactivation of adenosine by fat cells from hypothyroid rats. 608 4

It has been suggested that part of the increased beta-catecholamine responsiveness in hyperthyroid animals is due to a decrease in alpha-catecholamine action. The present results indicate that neither hyperthyroidism nor hypothyroidism altered the alpha 2-adrenergic inhibition of adenylate cyclase or the alpha 1-adrenergic stimulation of phosphatidylinositol turnover in adipocytes from the white adipose tissue of hamsters. No effect of hyperthyroidism was found on the Kd for binding of [3H]dihydroergocryptine or the number of binding sites in membranes prepared from hamster adipocyte tissue. The stimulation of cyclic AMP due to beta-catecholamines was enhanced in adipocytes from hyperthyroid hamsters, as was lipolysis. However, in adipocytes from hyperthyroid hamsters the maximal stimulation of cyclic AMP due to isoproterenol, ACTH or epinephrine plus yohimbine, as seen in the presence of adenosine deaminase and theophylline, was less than in adipocytes from euthyroid hamsters. The activation of adenylate cyclase by isoproterenol was the same in membranes from hyperthyroid as compared to those from euthyroid hamsters in the absence or presence of guanine nucleotides. These data suggest that thyroid status has little effect on alpha-catecholamine action by enhances the activation of lipolysis by beta-catecholamine agonists.
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PMID:Effect of thyroid status on alpha- and beta-catecholamine responsiveness of hamster adipocytes. 627 17

The anti-lipolytic effect of the adenosine analogue N6-L-phenylisopropyladenosine was studied with rat adipocytes incubated with a high concentration of adenosine deaminase (0.5 unit/ml, approx. 2.5 micrograms/ml) and concentrations of noradrenaline that were equieffective in different physiological states. These studies were performed to compare the fed and starved (24h) states and to compare a hypothyroid state (induced by feeding propylthiouracil + a low-iodine diet) with the euthyroid state. Starvation increased sensitivity of the cells to the lipolytic action of noradrenaline, while decreasing sensitivity to the antilipolytic action of phenylisopropyladenosine. Hypothyroidism resulted in decreased sensitivity to noradrenaline and increased sensitivity to phenylisopropyladenosine. Studies of the binding of [3H]phenylisopropyladenosine to adipocyte plasma membranes indicated heterogeneity of binding sites or negative co-operativity in the binding. Starvation did not change [3H]phenylisopropyladenosine binding to membranes, whereas hypothyroidism caused an unexpected decrease in both the number and affinity of the binding sites. These observations are discussed in terms of the dual regulation of adipose-tissue lipolysis by lipolytic and anti-lipolytic agents.
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PMID:Changes in the anti-lipolytic action and binding to plasma membranes of N6-L-phenylisopropyladenosine in adipocytes from starved and hypothyroid rats. 649 45

Male Wistar rats, 3 weeks old, were thyroidectomized surgically, kept for 1 month at 25 degrees C and then fasted for 3 days, with or without daily intraperitoneal injection of 3,5,3'-triiodo-L-thyronine (4.6 nmol T3/100 g body weight). Age-matched fed euthyroid rats were used as controls. All the experiments were carried out using isolated epididymal adipocytes. Basal lipolysis was higher during fasting in euthyroid or T3-treated adipocytes than in hypothyroid adipocytes. Adipocytes of fed hypothyroid rats were quite unresponsive to theophylline alone or combined with adrenaline or isoproterenol, whereas lipolysis was stimulated by these drugs in euthyroid or T3-treated adipocytes. Such a stimulated lipolysis was increased partially by fasting in hypothyroid adipocytes and was restored to a euthyroid level in T3-treated adipocytes. Lipolysis was more stimulated by adenosine deaminase in fasted euthyroid adipocytes than in fed ones. Hypothyroid and T3-treated adipocytes were unresponsive to adenosine deaminase except in fasted T3-treated rats. In these adipocytes, lipolysis was activated by the combination of adenosine deaminase plus theophylline. Finally, lipolysis was inhibited strongly in hypothyroidism while it was activated weakly by fasting. Lipolysis was inhibited slightly in fasted hypothyroid rats and thyroid hormone restored lipolysis. The findings are discussed in terms of the dual regulation of lipolysis by fasting and thyroid hormones.
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PMID:Influence of prolonged fasting on thyroid hormone modulation of lipolysis in isolated epididymal adipocytes of Wistar rats. 795 63

Hypothyroidism profoundly reduces the capacity of brown adipose tissue (BAT) to generate cAMP in response to adrenergic stimulation. Evidence obtained with isolated brown adipocytes suggests a postreceptor defect that offsets the hypothyroidism-induced increase in beta3-adrenergic receptors. The goal of the present studies was to identify the defect in the cAMP generation pathway for which we studied cAMP generation in isolated cells and purified BAT membranes from normal and hypothyroid rats. Studies with adenosine deaminase and the adenosine receptor-1 agonist r-phenyl isopropyl adenosine (R-PIA) show that hypothyroid cells are not more sensitive to adenosine (same EC50) but more inhibited by high concentrations of R-PIA. Pretreatment with pertussis toxin reduced the gap in cAMP generation between eu- and hypothyroid cells and the inhibition mediated by R-PIA, but did not normalize the cAMP response to forskolin in hypothyroid cells. Although purified euthyroid BAT membranes increased cAMP production with GTP concentrations up to submillimolar range, to plateau or slightly decrease at higher levels, hypothyroid membranes were weakly stimulated by low concentrations of GTP and markedly inhibited (>50%) at concentrations > or = 10(-4) M. When assayed at 0.3 mM ATP and 1 microM GTP, hypothyroid membranes actually generated more cAMP in response to forskolin, but this was reversed when GTP concentration was 1 mM. Immunoblotting studies showed no significant effects of hypothyroidism on the abundance of G(alpha)i or Gbeta subunits, and ADP ribosylation of G(alpha)i was only 45% increased in hypothyroidism in contrast to a 2.5-fold increase in hypothyroid white adipose tissue membranes from the same rats. Hypothyroid membranes also exhibited different kinetics regarding ATP, with higher cAMP generation at submillimolar concentrations but less at >1 mM ATP. Actually, at ATP concentrations >0.6 mM, cAMP generation was markedly inhibited in hypothyroid membranes. Fixing the concentration of free Mg++ in these experiments indicates that most of the inhibition seen in hypothyroid membranes is caused by ATP, whereas euthyroid membranes are more sensitive to changes in free Mg++. Ca++ +/- calmodulin did not stimulate adenylyl cyclase (AC) activity. On the contrary, AC activity was inhibited by Ca++ in a concentration-dependent manner, by as low as 100 nM free Ca++, and to greater extent in hypo- than in euthyroid membranes (maximal inhibition 60 vs. 25-30%). Our results suggest that, functionally, hypothyroidism causes a change in the AC of BAT membranes consistent with a relative or absolute increase in the type VI AC (AC-VI). The effects on this AC of nucleotides, Ca++, and Mg++ at concentrations prevailing in the hypothyroid brown adipocyte are probably the major factor in the reduced capacity of these cells to generate cAMP. These results also open the possibility of a novel, differential effect of thyroid hormone on AC expression, and support the concept that thyroid hormone affects the adrenergic signal transduction pathways in a tissue-selective manner.
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PMID:Effects of hypothyroidism on brown adipose tissue adenylyl cyclase activity. 894 Mar 79


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