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)

Previous studies have shown that platelets decrease 125I-labeled albumin permeability across confluent bovine pulmonary artery endothelial cell monolayers. In the current study, we addressed the role of platelets and platelet-derived adenosine (ADO) in vascular barrier function with cultured endothelial cells and isolated perfused lungs. Both 7 x 10(7) platelets/ml and conditioned media prepared from the same concentration of platelets reduced albumin permeability of endothelial monolayers by 37%. This activity was abolished by pretreatment of the platelets with adenosine deaminase (ADA). ADO (10(-7) M) added directly to the monolayer reduced permeability by 19%. Dipyridamole (10(-6) M), an inhibitor of facilitated ADO uptake, was used to evaluate the contribution of endothelial uptake of ADO in the platelet effect. Dipyridamole pretreatment of the endothelial monolayer did not alter the ability of platelets to decrease albumin permeability. Addition of either an A1- or A2-receptor-specific analogue of ADO to endothelial monolayers revealed that only the A1-analogue possessed permeability-decreasing activity. An isolated perfused guinea pig lung model was used to evaluate the effect of platelets on transvascular water flux as measured by the capillary filtration coefficient (Kf,c). Platelets (4.5 x 10(7) platelets/ml) added to the perfusate reduced Kf,c by 29%. Pretreatment of platelets with ADA abolished this response. The addition of ADO (10(-7) M) reduced Kf,c by 11%. Pulmonary vascular resistance was not changed by any intervention. Our results indicate that ADO is a component in platelet-mediated decreases both in albumin permeability across endothelial monolayers and of the capillary filtration coefficient in isolated perfused lungs.
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PMID:Role of adenosine in platelet-mediated reduction in pulmonary vascular permeability. 155 87

The effect of platelets on polymorphonuclear leukocytes (PMN) O2- production was examined using autologous sheep and human cell systems. Coincubation of sheep platelets with sheep PMNs in the absence of thrombin resulted in a significant inhibition in basal PMN O2- production. The platelet-derived inhibitory activity was released into the medium and could be destroyed by adenosine deaminase suggesting that the inhibitor was adenosine. Addition of alpha-thrombin or platelet activating factor (PAF) enhanced PMN O2- production but only when platelets were present. The enhancement of O2- production in response to thrombin was dependent upon the thrombin concentration and the platelet-PMN ratio. With a platelet: PMN ratio of 30: 1, addition of 10 nM thrombin to sheep cells resulted in a 5-fold increase in O2- production, whereas addition of 10 nM PAF caused a 2-fold increase in O2-. Addition of thrombin or PAF to either PMNs or platelets by themselves did not initiate an increase in O2- generation. The response of human cells was similar except that both thrombin and PAF triggered a 2-fold increase in PMN O2- production in the presence of platelets. The platelet-derived enhancement activity was not released into the medium and was not blocked by WEB 2086, NDGA, ETYA, aspirin or adenosine deaminase. The enhancement effect appeared to be localized to the platelet membrane and we believe requires platelet-PMN contact.
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PMID:Platelet modulation of neutrophil superoxide anion production. 216 Jan 33

Previous work has shown that platelet-derived adenine nucleotides modulate neutrophil superoxide anion (O2-) generation. Additional studies were undertaken to characterize the effects of authentic adenosine (ADO) and its nucleotide derivatives on the inflammatory functions of human neutrophils. Stimulus-specific inhibition of neutrophil O2- generation by ADO in response to FMLP was verified. In addition, the ability of ATP, ADP, and AMP to limit neutrophil O2- generation induced by FMLP (0.2 to 0.5 microM) was demonstrated. The concentration producing 50% inhibition for nucleotide inhibition of neutrophil O2- generation was in the rank order of ADO (0.1 microM) less than AMP (0.5 microM) less than ADP less than or equal to ATP (5 microM). Guanine and inosine nucleotides (0.01 to 100 microM) did not inhibit FMLP-stimulated neutrophil O2- generation. Neutrophil degranulation in response to FMLP was only modestly inhibited by adenine nucleotides and ADO. Adenosine and ADP failed to affect chemotaxis of neutrophils stimulated with FMLP. The inability of non-metabolizable analogs to mimic the inhibitory effects of authentic ATP or ADP on the neutrophil O2- response suggested that metabolism of added nucleotides is necessary for their effectiveness. Both TLC and HPLC confirmed that ATP and ADP were converted to AMP and ADO after their incubation with unstimulated or FMLP-activated neutrophils. The addition of adenosine deaminase to neutrophil reaction mixtures in which conversion of added nucleotides was apparent removed detectable ADO but failed to completely abrogate the inhibition of neutrophil O2- generation by accumulated AMP. The kinetics of inhibition of FMLP-induced neutrophil O2- generation by ATP and ADP also indicated that conversion of these nucleotides to ADO and/or AMP may be essential for their ability to reduce neutrophil responses.
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PMID:Regulation of human neutrophil functions by adenine nucleotides. 253 67

The cellular levels of the purine catabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and those for the pyrimidine activities thymidine phosphorylase and thymidine kinase isozymes have been measured concurrently in peripheral blood nucleated cells of patients with acute lymphoblastic leukaemia, chronic lymphocytic or prolymphocytic leukaemia and correlated with the spontaneous tritiated thymidine uptake of the isolated cells. Highest ADA levels occurred in T-ALL cells but considerable overlap of individual activities occurred for non-T, non-BALL, B-CLL and T-CLL cells. The levels of PNP showed no distinct discriminatory trend in cells of the lymphoid proliferative disorders examined. Thymidine phosphorylase activity was markedly reduced in T-ALL and T-CLL cells with a stepwise increase in the level of mean activities for non-T, non-B ALL, B-CLL and B-PLL cells to that of isolated normal peripheral blood lymphocytes. Spontaneous tritiated thymidine uptake of the abnormal lymphoid cells exhibited a correlation between cellular thymidine kinase isozyme 1 and elevated ADA levels. The use of ADA inhibitors together with thymidine infusion for the treatment of lymphoproliferative disorders is discussed.
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PMID:Purine and pyrimidine activities in acute and chronic lymphocytic leukaemia: relation to cellular proliferative status. 681 8

Platelets have been shown to protect isolated perfused rat hearts from injury and dysfunction after ischemia and reperfusion. We examined the role of platelet-derived adenosine in the cardioprotective effects of platelets against reperfusion injury. Isolated perfused rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. The buffer-perfused hearts developed dysfunction, as indicated by 40 +/- 4% decrease in force of cardiac contraction (FCC) and 24 +/- 3% increase in coronary perfusion pressure (CPP). Creatine kinase (CK) was released in coronary effluent during reperfusion, indicating myocardial injury. At the end of reperfusion, myocardial CK content and superoxide dismutase (SOD) activity were lower than in sham ischemia-reperfused hearts. Perfusion of hearts with washed platelets resulted in protection against myocardial dysfunction and injury after ischemia and reperfusion, indicated by preservation of FCC (-2 +/- 5%) and CPP (-3 +/- 2%) (both p < 0.01 vs. buffer-perfused hearts). Myocardial CK and SOD activity were also preserved, and release of CK in the coronary effluent was minimal (all p < 0.05 vs. buffer-perfused hearts). The cardioprotective effects of platelets were attenuated by preincubation of platelets with adenosine deaminase. Perfusion with adenosine or the adenosine2 receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2- methylphenyl)-ethyl]adenosine (DPMA) also protected heart from myocardial dysfunction and injury after ischemia and reperfusion. Both adenosine and DPMA had salutary effects on indexes of cardiac injury. Platelet-derived adenosine contributes at least in part to the cardioprotective effects of platelets against ischemia and reperfusion in isolated rat heart.
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PMID:Platelet-derived adenosine contributes to the cardioprotective effects of platelets against ischemia-reperfusion injury in isolated rat heart. 753 56

The effect of human platelets on chemoattractant-induced generation of oxygen metabolites in neutrophils was investigated, using luminol-enhanced chemiluminescence (CL). Resting platelets inhibited the extracellular, but not the intracellular, production of oxygen radicals in formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe)-stimulated neutrophils. Maximal effect was obtained at the physiological neutrophil/platelet ratio of 1/50. Similar results were acquired by adding supernatants of platelets, indicating a role for a soluble factor. Removal of extracellular adenosine by adenosine deaminase (ADA), or blocking of adenosine-receptors by theophylline, antagonized the inhibitory effects of platelets (or the equivalent supernatant) on the neutrophil respiratory burst. In contrast, accumulation of adenosine by apyrase enhanced the inhibition. Exogenous adenosine mimicked the effects of platelets on the fMet-Leu-Phe-induced respiratory burst. To further assess the role of platelet-derived adenosine, the platelets were fixed with paraformaldehyde. We found that fixed platelets, as well as their supernatant, inhibited the fMet-Leu-Phe-induced CL-response to the same extent as viable cells. These effects were also reversed by ADA and theophylline, respectively. A prior removal of adenosine in the platelet suspension by ADA, followed by treatment with erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) to inactivate ADA, did not reverse the inhibitory action of platelets on the fMet-Leu-Phe-induced CL-response in neutrophils. However, if adenosine receptors of neutrophil at the same time were blocked with theophyline, the inhibition was significantly reduced. Platelets markedly increased the generation of adenosine in a neutrophil suspension. The effect was antagonized by S-(4-Nitrobenzyl)-6-thioguanosine (NBTG), but unaffected by alpha, beta-methyl-eneadenosine5'diphosphate (AMP-CP), indicating that the platelet-dependent accumulation of adenosine is due to an increased release of endogenous adenosine from neutrophils and not to a degradation of extracellular AMP. In correlation, NBTG, but not AMP-CP, reversed the platelet-mediated inhibition of the fMet-Leu-Phe-induced CL-response in neutrophils. Consequently, these data suggest that a platelet-derived factor increases the release of endogenously formed adenosine from neutrophils, terminating the production of oxygen radicals. The inhibition of oxidase activity was also associated with a platelet-induced polymerization of actin in the margin of the neutrophils. Treatment of neutrophils with cytochalasin B reversed the effects of platelets, both on F-actin content and CL-response. In summary, resting platelets limit the release of oxygen radicals from chemoattractant-stimulated neutrophils, thus preventing excessive damage to host tissues in the vascular space. This effect is suggested to be associated with an increase generation of neutrophil-derived adenosine enhancing an autoregulatory inhibitory pathway, and a peripheral accumulation of actin filaments forming a barrier for extracellular release of reactive oxygen radicals.
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PMID:Release of oxygen metabolites from chemoattractant-stimulated neutrophils is inhibited by resting platelets: role of extracellular adenosine and actin polymerization. 863 3

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