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 phenotypic distribution and gene frequencies of haptoglobin (Hp), transferrin (Tf), group specific component (Gc), cholinesterase (Cho E2), and alpha1-antitrypsin (Pi) in plasma proteins, and phosphoglucomutase (PGM), 6-phosphogluconate dehydrogenase ((6-PGD), esterase D (Es D), phosphohexose isomerase (PHI), adenosine deaminase (ADA) and acid phosphatase (AcP) in red cells were studied in 127 atopic, asthmatic patients. The gene frequencies were compared with normal groups. The phenotypic distribution of the Pi system in atopic patients was somewhat different from the normal. No significant differences were found between the two groups in protein systems or in enzyme systems, except Pi systems. In conclusion, except for the Pi system, no definite association between polymorphic traits and atopic asthma was found in this study.
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PMID:The distribution of polymorphic traits in atopic asthmatic patients. 108 Mar 21

The effect of aminophylline administered intravenously in dose 250 mg on plasma oxypurines (hypoxanthine and xanthine) concentration as well as on plasma adenosine deaminase activity and plasma AMP deaminase activity was studied in 17 patients with bronchial asthma or chronic cor pulmonale. Initial plasma oxypurines concentration was 47.5 +/- 10.4 mumol/l and one hour after aminophylline administration decreased significantly (p less than 0.001) to the value 40.3 +/- 8.8 mumol/l. Plasma adenosine deaminase activity increased significantly from 4.74 +/- 2.3 IU to 6.9 +/- 2.77 IU (p less than 0.01), while plasma AMP deaminase activity did not change. The above results suggest indirectly that intravenous administration of aminophylline decreases serum adenosine concentration in studied patients.
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PMID:[The effect of aminophylline on plasma oxypurines in patients with bronchial asthma or cor pulmonale]. 188 28

1. We investigated effects of theophylline (widely used for the treatment of asthma) and enprofylline (a new xanthine derivative with negligible adenosine antagonism) on O2- production by human neutrophils with n-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulation. 2. Therapeutic concentrations of theophylline (1-100 mumol/L) enhanced O2- production, maximally by 43.1 +/- 24.4% at 30 mumol/L; the same concentrations of enprofylline inhibited O2- production. 3. When each agent was administered after pre-incubation with adenosine deaminase (ADA) (0.1 U/mL), O2- production was inhibited in a concentration-dependent manner in comparison with that under administration of ADA alone. 4. These results suggest that the difference of effects in the two xanthine derivatives at therapeutic concentrations might be due to the presence or absence of adenosine antagonism.
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PMID:Comparison of theophylline and enprofylline effects on human neutrophil superoxide production. 196 97

Eosinophils may play a critical role in asthma and bronchial hyperresponsiveness, yet the effect of theophylline on their function is not certain. We have examined the effects of theophylline on opsonized zymosan-induced superoxide anion (O2-) release from guinea pig eosinophils harvested from the peritoneal cavity and from human eosinophils obtained by differential centrifugation of blood from patients with peripheral eosinophilia. Theophylline at high concentration (10(-3) M) inhibited O2- release by 27.6 +/- 9.4% (mean +/- SEM, p less than 0.05), whereas at clinically relevant concentrations (10(-6) and 10(-5) M), it significantly potentiated this by 26.8 +/- 9.9% (p less than 0.05) and 36.9 +/- 6.3% (p less than 0.01), respectively. 8-phenyltheophylline (10(-7) to 10(-3) M), which like theophylline inhibits adenosine receptors but does not inhibit phosphodiesterase activity, produced potentiation at all concentrations. Preincubation of eosinophils with adenosine deaminase (0.1 U/ml) enhanced O2- release by 72.4 +/- 15.2% (p less than 0.01), whereas addition of adenosine (3 x 10(-8) to 10(-6) M) reversed the potentiation induced by theophylline (10(-5) M) in a concentration-dependent manner. Inhibition was greater with the A2-selective analog N-ethylcarboxamide adenosine than the A1-selective analog phenylisopropyladenosine, suggesting that A2-receptors are involved. In human eosinophils we have demonstrated a similar effect of theophylline and adenosine on O2- release. Our results indicate that therapeutic concentrations of theophylline may potentiate eosinophil activation in vivo by competing with circulating adenosine for eosinophil A2-receptors. This would be consistent with the lack of effect of theophylline on bronchial hyperresponsiveness, which may be related to eosinophilic inflammation.
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PMID:Effect of theophylline and adenosine on eosinophil function. 254 25

Wheezing in children is characterized by at least two major syndromes: "wheezing associated with respiratory infections" and "atopic asthma." The distinction between these two forms is not easy as similarities exist between them. The purpose of this study was to try to differentiate between them. We determined the phenotype of adenosine deaminase (ADA) in 291 children ages 1 mo to 15 yr who had been affected by attacks of wheezing recently requiring clinical attention. The results demonstrated that the frequency of 2-1 ADA phenotype was significantly reduced in wheezers compared to control subjects. Among wheezers, the 2-1 ADA phenotype was normally represented under 5 yr of age but was particularly rare among asthmatic children 5 to 15 yr old. Thus ADA phenotypes may represent a genetic basis for some of the heterogeneity of the asthma syndromes in children.
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PMID:A genetic basis for heterogeneity of asthma syndrome in pediatric ages: adenosine deaminase phenotypes. 673 86

Adenosine may play a role in asthma as a pro-inflammatory mediator. In this study, the release of adenosine from human sensitized lung fragments and its effect on antigen-induced histamine and leukotriene release has been explored. Antigen challenge increased histamine and leukotriene release five-fold but was without effect on adenosine release. In contrast, the adenosine deaminase inhibitor EHNA (10 microM) and the adenosine kinase inhibitor 5-iodotubericidin (10 microM) increased adenosine concentration 45-fold (P < or = 0.001; n = 4 patients). Of major interest was the finding that the non-selective, cell impermeant, adenosine antagonist pSPT (100 microM) decreased histamine and leukotriene release by 25% (P < or = 0.001) and 40%, respectively (P < or = 0.05; n = 9 patients). Additionally, the non-selective adenosine agonist NECA (10 microM) markedly inhibited antigen-induced leukotriene release by 80-90% (P < or = 0.001) and marginally inhibited histamine release by approximately 10% (P < or = 0.05; n = 9); the A2a-selective agonist DPMA (10 microM) was without effect on either histamine or leukotriene release. These results are consistent with adenosine having a biphasic effect on antigen-induced mediator release with low concentrations potentiating release and high concentrations inhibiting release. The overall stimulatory effect of endogenous adenosine supports the proposal that adenosine may act as a pro-inflammatory mediator in asthma.
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PMID:Release of adenosine from human sensitized lung fragments and its effect on antigen-induced mediator release. 894 10

The present study was designed to determine whether endogenous and exogenous adenosine modulates endothelin (ET)-induced bronchoconstriction. Exogenous adenosine enhances ET-induced bronchoconstriction. Following pretreatment with adenosine deaminase and theophylline to eliminate or antagonize endogenous adenosine, ET-1-induced bronchoconstriction was significantly attenuated, but not that of ET-3. In conclusion, this is the first report of an enhancement of ET-induced bronchoconstriction of guinea pig airways by endogenous and exogenous adenosine. Our findings may be useful in designing specific adenosine receptor antagonists as therapeutic agents in the management of bronchial asthma.
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PMID:Adenosine modulates endothelin-induced bronchoconstriction in guinea pig airway. 898 Apr 68

Adenosine may play a role in asthma by enhancing inflammatory mediator release from lung mast cells. In this study, we investigated whether adenosine is released from cultured rat basophilic leukaemia (RBL-2H3) cells in response to antigen challenge and whether released adenosine enhances mediator release. RBL-2H3 cells closely resemble mucosal mast cells, the most common type of mast cell in lung tissue, and they express adenosine A3 receptors (which have been associated with asthma). Measurement of adenosine in RBL-2H3 cell incubation medium was possible if adenosine metabolism was inhibited by EHNA (10 microM; an adenosine deaminase inhibitor) and 5-iodotubericidin (5-IT; 10 microM; an adenosine kinase inhibitor). Basal adenosine concentration increased up to 1.0 microM during a 90 min incubation; after antigen challenge, adenosine concentration was increased by 0.3-0.4 microM above basal. Antigen-induced adenosine release ranged from 30-70 nmol/1.25x10(6) cells. Antigen-induced mediator release (beta-hexosaminidase and [3H]5-hydroxytryptamine) was increased by APNEA, an adenosine A3 receptor agonist (EC50 approximately 20 nm) but inhibited by EHNA and 5-IT, despite increased adenosine levels. This inhibition was not blocked by the adenosine A1/A2 receptor antagonist DPSPX (5 microM). Therefore, it is unlikely to be related to adenosine receptor activation. In conclusion, although our data provide no direct support for a positive feedback effect of adenosine on mast cell mediator release, the observation that IgE receptor stimulation increases adenosine production in cells which express stimulatory A3 receptors is consistent with this hypothesis.
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PMID:Evidence that IgE receptor stimulation increases adenosine release from rat basophilic leukaemia (RBL-2H3) cells. 980 62

Adenosine is a mediator of bronchoconstriction in asthmatics and is believed to mediate its effects through adenosine receptor activation in inflammatory cells. In this study, we identify human airway smooth muscle (ASM) as a direct target of adenosine. Acute exposure of human ASM cultures to adenosine receptor (AR) agonists resulted in rapid accumulation of cyclic adenosine monophosphate (cAMP) with a pharmacologic profile consistent with A(2b)AR activation. Little or no evidence of A1AR or A3AR expression was suggested on acute addition of various AR ligands, although a low level of A1ARs was identified in radioligand binding studies. Treatment with adenosine deaminase suggested that human ASM cultures secrete adenosine that feeds back on A(2b)ARs and regulates basal cAMP levels as well as a small degree of A(2b)AR, beta(2)AR, and prostaglandin E(2) receptor desensitization. When subjected to chronic treatment with AR agonists or agents that enhance accumulation of endogenous, extracellular adenosine, a dual effect of A(2b)AR desensitization and adenylyl cyclase (AC) sensitization was observed. This AC sensitization was eliminated by pertussis toxin and partially reversed by the A1AR antagonist 8-cyclopentyl-1,3-dipropylxanthine, suggesting a contributory role for the A1AR. Overexpression of A1ARs and A(2b)ARs in human ASM cultures resulted in differential effects on basal, agonist-, and AC-mediated cAMP production. These data demonstrate that human ASM is a direct target of exogenous and autocrine adenosine, with effects determined by differential contributions of A(2b) and A1 adenosine receptors that are time-dependent. Accordingly, the relative distribution and activation of AR subtypes in ASM in vivo may influence airway function in diseases such as asthma and warrant consideration in therapeutic strategies that target ARs or alter nucleotide/ nucleoside levels in the airway.
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PMID:Regulation of G protein-coupled receptor-adenylyl cyclase responsiveness in human airway smooth muscle by exogenous and autocrine adenosine. 1115 49

Adenosine has been implicated as a modulator of inflammatory processes central to asthma. However, the molecular mechanisms involved are poorly understood. We used Atlas mouse cDNA arrays to analyze differential gene expression in association with lung inflammation resulting from elevated adenosine in adenosine deaminase (ADA)-deficient mice. We report that of the 1,176 genes on the array, the expression patterns of 280 genes were consistently altered. Of these genes, the steady-state levels of 93 genes were upregulated and 29 were downregulated. We also show that lowering adenosine levels with ADA enzyme therapy has striking effects on gene expression that may be associated with resolution of pulmonary eosinophilia. In addition, we confirmed the nucleic acid and protein expression of vascular endothelial growth factor and monocyte chemoattractant protein-3, two candidate genes that may be regulated by adenosine. In conclusion, high-throughput profiling of gene expression by cDNA array hybridization has provided an overview of critical regulatory genes involved in airway inflammation in ADA-deficient mice. These mice will serve as a useful in vivo model for characterizing molecular mechanisms of adenosine-mediated lung damage.
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PMID:Gene expression profiling in inflammatory airway disease associated with elevated adenosine. 1179 19


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