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)

The vasodilatory effect of adenosine and some related compounds were studied in subcutaneous adipose tissue in situ. The effects of three drugs that inhibit adenosine elimination; two adenosine uptake blockers, dipyridamole and dilazep, the adenosine deaminase inhibitor, EHNA, were also studied. Plasma levels of adenosine were simultaneously determined by HPLC. Adenosine was a potent vasodilator and 2- and 6-substituted analogues were even more potent. Tissue blood flow was linearly related to the venous plasma concentrations of adenosine. An elevation of adenosine in plasma from 0.25 to 0.5 Mu M enhanced blood flow by approximately 50%. A further increase to 1 mu M was associated with a doubling of adipose tissue blood flow. Adenosine also increased the vascular conductance and the capillary filtration coefficient, indicating that is is active on all sections of the vascular bed. Theophylline and caffeine (30- 100 mu M in arterial plasma) antagonized the vasodilatory effect of exogenous adenosine, abolished vasodilation due to EHNA+dipyridamole and reduced resting blood flow. The results suggest that adenosine plays a physiological role in regulating adipose tissue blood flow.
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PMID:Role of adenosine in adipose tissue circulation. 729 98

We employed intracoronary infusions of calf intestine adenosine deaminase (ADA) to test the hypothesis that adenosine regulates coronary blood flow during myocardial reactive hyperemia (RH). Infusions of 4.5 U ADA/min per kg body weight into the left circumflex coronary artery of 10 open-chest dogs reversibly reduced repayment of flow debt by 30-39% (P less than 0.05) following 5-, 10-, 15-, 20-, and 30-second coronary occlusions, the percentage reduction being independent of occlusion length. ADA reduced peak RH flow rate (17%, P less than 0.05) only after 5-second occlusions. Intracoronary infusions of [131]ADA in seven dogs produced interstitial ADA concentrations between 1.2 and 13.1 U/ml in perfused myocardium and, in five of these dogs, 131I activity in the cardiac node was 1.8-35 times that of contiguous mediastinal tissue. Theophylline, a specific adenosine antagonist, reduced repayment of flow debt by 27-36% (P less than 0.02) in eight dogs, an effect similar to that of ADA. In six other dogs, ADA plus theophylline did not reduce RH flow debt repayment below that produced by ADA alone. This experiment confirms the contribution of adenosine to myocardial RH but shows that this nucleoside accounts for but a third of volume flow. Other, as yet unidentified, factors are collectively more important.
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PMID:Intracoronary adenosine deaminase reduces canine myocardial reactive hyperemia. 730 43

The possible role of brain adenosine in acute ethanol-induced alteration in glucose utilization in the whole brain, as well as in the specific brain areas (cerebellum and brain stem), was investigated. Mice were killed 20-min postethanol, and the fresh tissue slices (300 microns) of brain and/or specific brain areas were incubated for 100 min in a 5.5 mM glucose medium in Warburg flasks using [6-(14)C]glucose as a tracer. Trapped 14CO2 was counted to estimate glucose utilization. Ethanol (2 g/kg, i.p.) markedly increased the glucose utilization in whole brain and in both motor areas of brain. Theophylline (50 mg/kg, i.p.), an adenosine antagonist, significantly reduced ethanol-induced increase in glucose utilization in whole brain, as well as in brain areas. However, adenosine agonist N6-cyclohexyladenosine (CHA; 0.1 mg/kg, i.p.) on the contrary, significantly accentuated ethanol-induced increase in glucose utilization in these tissues that was nearly completely blocked by theophylline pretreatment. Theophylline alone did not produce any significant change in glucose utilization, whereas CHA alone (in vivo and in vitro) significantly increased glucose utilization, as well as ethanol-induced increase in glucose utilization in an additive manner. Relevant supportive data were obtained by experiments in which adenosine deaminase (ADA), p-sulfophenyltheophylline (8-SPT), and CHA were administered in vitro to the slice preparations. Both ADA and 8-SPT were effective in almost completely blocking the ethanol-induced increase in glucose utilization, whereas CHA further enhanced the ethanol-induced increase in glucose utilization in an additive manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible central adenosinergic modulation of ethanol-induced alterations in [14C]glucose utilization in mice. 757 8

Freshly drawn blood samples from seven female and seven male healthy donors were used. Arginine8-vasopressin (AVP) effects on platelet aggregation and serotonin (5-HT) release were examined in adenosine-depleted platelet-rich plasma (PRP) and PRP containing normal amounts of plasma adenosine. No significant differences in the plasma adenosine levels were noted between female (208 +/- 90 nM) and male (239 +/- 85 nM) subjects, but significant differences in AVP-induced platelet aggregation and 5-HT release were noted between female and male subjects. In adenosine-depleted PRP, platelets from most female donors could be aggregated irreversibly at low levels of AVP (18 mU/ml, or 42 nM), whereas platelets from most male donors responded poorly and caused only reversible aggregation at much higher AVP levels (108-720 mU/ml PRP or 252-1,680 nM). In contrast, in PRP containing normal amounts of adenosine, AVP response to induce platelet aggregation was much weaker, demonstrating that adenosine acts as a natural modulator of AVP actions. Theophylline and a relatively selective A2 antagonist DMPX (3,7-dimethyl-1-propargylxanthine) attenuate the plasma adenosine effects causing potentiation in AVP activity on platelet aggregation. These studies suggest that agents that can increase plasma adenosine levels (e.g., inhibitors of nucleoside transport and adenosine deaminase), or adenosine receptor antagonists, may have potential therapeutic uses in modulation of AVP actions in the body. Furthermore, the human platelet serves as a suitable pharmacologic model to study interactions between biologically produced adenosine and AVP.
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PMID:Modulation of vasopressin actions on human platelets by plasma adenosine and theophylline: gender differences. 833 6

Theophylline at low doses (10 mg/kg/day p.o.) under long-term conditions (for 16 consecutive days) increased the adenosine deaminase (ADA) activity in spleen and thymus of adult male albino rats without changing its hepatic ADA activity. Treatment with high doses (20 mg/kg/day p.o.) under similar conditions, on the other hand, decreased the splenic and hepatic ADA activity and increased the thymic ADA activity. This induction of thymic ADA activity, however, was significantly less than that observed with low doses of theophylline. The plasma corticosterone level was increased without changing its adrenal level under similar conditions. This study, thus, indicates that long-term theophylline treatment may potentiate or suppress the immune response, depending on the dose, through the tissue (liver/spleen/thymus)-specific modulation of ADA activity and plasma corticosterone status.
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PMID:Theophylline-induced changes in mammalian adenosine deaminase activity and corticosterone status: possible relation to immune response. 920 66

This study was designed to determine whether theophylline would augment granulocyte apoptosis via a mechanism of adenosine A2A receptor antagonism. A selective adenosine A2 receptor agonist (CGS-21680, 1 microM) exhibited the most efficient potency for decreasing neutrophil apoptosis for 16 h from 63+/-5 to 19+/-4% (P < 0.001); it exerted poor and adverse effects on eosinophil survival. A selective protein kinase A inhibitor KT-5720 (10 microM) reversed the capacity of dibutyryl cAMP but not CGS-21680 to induce an inhibitory effect on neutrophil apoptosis, suggesting that occupancy of adenosine A2 receptors inhibit neutrophil apoptosis by a cAMP-independent mechanism. Theophylline derivatives show the following pattern of potency for inducing neutrophil apoptosis competing with CGS-21680: 8-phenyltheophylline = 8-p-sulfophenyltheophylline > theophylline >> enprofylline. This pattern is consistent with the affinity established for A2A receptors. Theophylline demonstrated an additive effect to that of anti-Fas antibody (CH11, 1 microg/mL) in inducing neutrophil apoptosis, but not to that of adenosine deaminase or KF-17837 (a selective A2 receptor antagonist; 1 microM), suggesting conflicting effects on the receptor antagonism. These findings suggest that theophylline has an immunomodulatory action on neutrophil apoptosis via a mechanism of A2A antagonism.
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PMID:Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism. 1077 Feb 86

Cerebral ischemia studies demonstrating that stimulation of adenosine A1 receptors by either endogenously released adenosine or the administration of selective receptor agonists causes significant reductions in the morbidity and mortality associated with focal or global brain ischemias have triggered interest in the potential of purinergic therapies for the treatment of traumatic injuries to the brain and spinal cord. Preliminary findings indicate that activation of A1 adenosine receptors can ameliorate trauma-induced death of central neurons. Other avenues of approach include the administration of agents which elevate local concentrations of adenosine at injury sites by inhibiting its metabolism to inosine by adenosine deaminase, rephosphorylation to adenosine triphosphate by adenosine kinase; or re-uptake into adjacent cells. Amplification of the levels of endogenously released adenosine in such a 'site and event specific' fashion has the advantage of largely restricting the effect of such inhibitors to areas of injury-induced adenosine release. Another approach involving purinergic therapy has been applied to the problem of respiratory paralysis following high spinal cord injuries. In this instance, the adenosine antagonist theophylline has been used to enhance residual synaptic drive to spinal respiratory neurons by blocking adenosine A1 receptors. Theophylline induced, and maintained, hemidiaphragmatic recovery for prolonged periods after C2 spinal cord hemisection in rats and may prove to be beneficial in assisting respiration in spinal cord injury patients.
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PMID:Adenosine and neurotrauma: therapeutic perspectives. 1132 May 97

Mice rendered adenosine deaminase-deficient manifest an 'asthma' phenotype in the lungs that includes mast cell degranulation, eosinophilia, mucus hypersecretion and bronchial hyperresponsiveness. These changes can be reversed by enzyme therapy with adenosine deaminase, and attenuated by theophylline. Theophylline also blocks the pro-inflammatory effects of adenosine in allergen-challenged mice. Adenosine A(2A) receptors are an essential part of the physiological negative feedback mechanism for limitation and termination of both tissue-specific and systemic inflammatory responses. In recent clinical studies, increases in plasma adenosine have been shown to accompany exercise-induced asthma, and adenosine concentrations in exhaled breath condensate are increased in asthmatics. These new data provide support for a key role for adenosine in asthma, which has become increasingly persuasive in recent years. The evidence is now convincing, and the time has come for the asthma community to give its full support to the design and evaluation of molecules that mimic or block the biological effects of adenosine as potential novel therapeutics for this condition.
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PMID:The case for a role for adenosine in asthma: almost convincing? 1281 Jan 90


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