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 activity of the enzyme purine metabolism (5'-nucleotidase, adenosine deaminase, xanthine oxidase and the content of uric acid, i.e. the final product of the purine metabolism) were determined in lymphocytes, eosinophiles and blood serum of patients with bronchial asthma. The activity of 5'-nucleotidase in lymphocytes, eosinophiles and blood serum of patients with bronchial asthma was found to be reduced by 5-7-% as compared with the controls. The activity of adenosine deaminase in lymphocytes, eosinophiles and blood serum was found to be reduced in a majority of patients. An increased activity of adenosine deaminase was higher in lymphocytes and blood serum of 38% of the examined patients. The activity of xanthine oxidase in lymphocytes and eosinophiles of patients exceeded by 2.4 and 1.7 times the control value, respectively. The content of urine acid was found to be increased, in bronchial asthma, by 2.7 times. Consequently, the balance of enzyme reactions of the purine metabolism is impaired in bronchial asthma, and there is an accumulation of urine acid.
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PMID:[Enzymes of purine metabolism of lymphocytes and eosinophiles in bronchial asthma]. 1277 69

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

Adenosine has been implicated to play a role in asthma in part through its ability to influence mediator release from mast cells. Most physiological roles of adenosine are mediated through adenosine receptors; however, the mechanisms by which adenosine influences mediator release from lung mast cells are not understood. We established primary murine lung mast cell cultures and used real-time RT-PCR and immunofluorescence to demonstrate that the A(2A), A(2B), and A(3) adenosine receptors are expressed on murine lung mast cells. Studies using selective adenosine receptor agonists and antagonists suggested that activation of A(3) receptors could induce mast cell histamine release in association with increases in intracellular Ca(2+) that were mediated through G(i) and phosphoinositide 3-kinase signaling pathways. The function of A(3) receptors in vivo was tested by exposing mice to the A(3) receptor agonist, IB-MECA. Nebulized IB-MECA directly induced lung mast cell degranulation in wild-type mice while having no effect in A(3) receptor knockout mice. Furthermore, studies using adenosine deaminase knockout mice suggested that elevated endogenous adenosine induced lung mast cell degranulation by engaging A(3) receptors. These results demonstrate that the A(3) adenosine receptor plays an important role in adenosine-mediated murine lung mast cell degranulation.
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PMID:Activation of murine lung mast cells by the adenosine A3 receptor. 1281 16

Adenosine signaling has been implicated in chronic lung diseases such as asthma and chronic obstructive pulmonary disease; however, the specific roles of the various adenosine receptors in processes central to these disorders are not well understood. In this study, we have investigated the role(s) of the A(3) adenosine receptor in adenosine-dependent pulmonary inflammation observed in adenosine deaminase (ADA)-deficient mice. The A(3) receptor (A(3)R) was found to be expressed in eosinophils and mucus-producing cells in the airways of ADA-deficient mice. Treatment of ADA-deficient mice with MRS 1523, a selective A(3)R antagonist, prevented airway eosinophilia and mucus production. Similar findings were seen in the lungs of ADA/A(3) double knockout mice. Although eosinophils were decreased in the airways of ADA-deficient mice following antagonism or removal of the A(3)R, elevations in circulating and lung interstitial eosinophils persisted, suggesting signaling through the A(3)R is needed for the migration of eosinophils into the airways. These findings identify an important role for the A(3)R in regulating lung eosinophilia and mucus production in an environment of elevated adenosine.
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PMID:A3 adenosine receptor signaling contributes to airway inflammation and mucus production in adenosine deaminase-deficient mice. 1524 Jul 34

Adenosine is a ubiquitous biological mediator with the capacity to produce both pro- and anti-inflammatory effects in tissues. Proinflammatory and bronchoconstrictive actions of adenosine in the asthmatic lung are well recognized, with the latter being mediated, in part, through A(1) receptor activation on airway smooth muscle. In this issue of the JCI, Sun et al. report findings in adenosine deaminase-deficient mice that suggest the occurrence of anti-inflammatory actions of adenosine in the lung, mediated through A(1) adenosine receptors on macrophages. Here we discuss the history of the study of adenosine receptor ligands for asthma and how enhanced understanding of adenosine receptor biology may aid in the rational exploitation of these receptors as therapeutic targets.
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PMID:A1 antagonism in asthma: better than coffee? 1563 Apr 42

Adenosine is a signaling nucleoside that has been implicated in the regulation of asthma and chronic obstructive pulmonary disease. Adenosine signaling can serve both pro- and anti-inflammatory functions in tissues and cells. In this study we examined the contribution of A(1) adenosine receptor (A(1)AR) signaling to the pulmonary inflammation and injury seen in adenosine deaminase-deficient (ADA-deficient) mice, which exhibit elevated adenosine levels. Experiments revealed that transcript levels for the A(1)AR were elevated in the lungs of ADA-deficient mice, in which expression was localized predominantly to alveolar macrophages. Genetic removal of the A(1)AR from ADA-deficient mice resulted in enhanced pulmonary inflammation along with increased mucus metaplasia and alveolar destruction. These changes were associated with the exaggerated expression of the Th2 cytokines IL-4 and IL-13 in the lungs, together with increased expression of chemokines and matrix metalloproteinases. These findings demonstrate that the A(1)AR plays an anti-inflammatory and/or protective role in the pulmonary phenotype seen in ADA-deficient mice, which suggests that A(1)AR signaling may serve to regulate the severity of pulmonary inflammation and remodeling seen in chronic lung diseases by controlling the levels of important mediators of pulmonary inflammation and damage.
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PMID:A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury. 1563 Apr 34

We carried out a study of adenosine deaminase (ADA) and MN blood group genetic polymorphisms in relation to past malarial morbidity in Sardinia and in relation to susceptibility to allergic asthma (a Th2 disorder) and Crohn's disease (a Th1 disorder) in the population of Rome. Eight hundred and eight schoolchildren, aged 7--14 years from 14 Sardinian villages located in the central area of the island, were considered. One hundred and twenty-two children with allergic asthma and 39 adult patients with Crohn's disease from the population of Rome were also studied. The data suggest an interaction between the two systems concerning resistance/susceptibility, both to malaria and to the diseases considered. In Sardinia, the frequency of the *L(M)/ADA*2 gametic type is negatively correlated with past malarial endemia, suggesting an increased susceptibility to malaria leading to its decrease in areas with high malarial endemia. In Rome, this gametic type is correlated negatively to allergic asthma and positively to Crohn's disease, suggesting a protective effect against allergic asthma and increased susceptibility to Crohn's disease.
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PMID:Adaptation to past malarial endemia and susceptibility to common diseases in modern populations: a study of adenosine deaminase and MN blood group genetic polymorphisms. 1576 57

Pulmonary fibrosis is a common feature of numerous lung disorders, including interstitial lung diseases, asthma, and chronic obstructive pulmonary disease. Despite the prevalence of pulmonary fibrosis, the molecular mechanisms governing inflammatory and fibroproliferative aspects of the disorder are not clear. Adenosine is a purine-signaling nucleoside that is generated in excess during cellular stress and damage. This signaling molecule has been implicated in the regulation of features of chronic lung disease; however, the impact of adenosine on pulmonary fibrosis is not well understood. The goal of this study was to explore the impact of endogenous adenosine elevations on pulmonary fibrosis. To accomplish this, adenosine deaminase (ADA)-deficient mice were treated with various levels of ADA enzyme replacement therapy to regulate endogenous adenosine levels in the lung. Maintaining ADA-deficient mice on low dosages of ADA enzyme therapy led to chronic elevations in lung adenosine levels that were associated with pulmonary inflammation, expression of profibrotic molecules, collagen deposition, and extreme alteration in airway structure. These features could be blocked by preventing elevations in lung adenosine. Furthermore, lowering lung adenosine levels after the establishment of pulmonary fibrosis resulted in a resolution of fibrosis. These findings demonstrate that chronic adenosine elevations are associated with pulmonary fibrosis in ADA-deficient mice and suggest that the adenosine functions as a profibrotic signal in the lung.
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PMID:Adenosine-dependent pulmonary fibrosis in adenosine deaminase-deficient mice. 1603 38

Recent studies suggest that genetic polymorphism modulates immunoglobulin E (IgE)-mediated atopic reactions. Adenosine is an important local hormone influencing immune function and tissue reactivity; because adenosine concentration is regulated by adenosine deaminase (ADA), we have investigated the possible effect of ADA polymorphism on the relationship between IgE and positive prick test. A random sample of 160 schoolchildren from the population of Viterbo (Italy) were studied. Prick testing was performed with a panel of local allergens. Total IgE assay was performed according to standard clinical procedure. ADA phenotype was determined according to Spencer et al. A highly significant correlation between prick test and IgE was observed. However, the strength of correlation was moderate (eta2 = 0.16), indicating that positive prick testing depends on other variables besides IgE. The relationship between IgE and positive prick testing is stronger in carriers of ADA*2 allele than in ADA*1/*1 subjects. Also, sensitivity and predictive values are higher in ADA*2 carriers than in homozygous ADA*1/*1 children. The data suggest that the effect of IgE level on local reactivity is influenced by ADA polymorphism; at low level of IgE, the presence of the ADA*2 allele seems to protect from positive prick testing.
Allergy Asthma Proc
PMID:Adenosine deaminase polymorphism and the relationship of total immunoglobulin E with skin prick test: a study on school children. 1672 28

A case of adenosine deaminase (ADA) deficiency is described briefly. The clinical characteristics, pathogenesis, diagnosis, and management of this disease are discussed, followed by clinical pearls and pitfalls. ADA deficiency was identified in 1972 as a cause of severe combined immunodeficiency (SCID) and its incidence is approximately 1/10(6). This defect accounts for approximately 17% of all SCIDs and 50% of all autosomal recessive SCIDs. The patients typically have impaired immune function with recurrent severe infections, diarrhea, and failure to thrive. Because death occurs within a few months if untreated, it is a medical emergency. There are certain distinguishing features of ADA deficiency, including multiple skeletal abnormalities of chondro-osseous dysplasia on radiographic examination. ADA deficiency causes profound lymphopenia with all cells lines affected and is known as the T-B-NK-SCID type. The diagnosis of ADA deficiency requires measurements of plasma ADA and of deoxyadenosine metabolites. More than 67 mutations have been described, with 41 being missense mutations, which are more deleterious. The metabolic basis of the immunodeficiency is likely related to the sensitivity of lymphocytes to the accumulation of the aberrant ADA substrates, e.g., adenosine and 2'-deoxyadenosine. Intravenous immunoglobulin and antibiotics prophylaxis remains the mainstay of treatment with stem cell transplant being the initial management of choice.
Allergy Asthma Proc
PMID:Severe combined immune deficiency in an adenosine deaminase-deficient patient. 1672 39


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