Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 53-year-old woman was admitted to our hospital due to high fever, arthralgia and skin rash. Main laboratory data included the following: WBC 17,100/mm, GOT 58 U, GPT 47 U, LDH 1,510 U, ferritin 19,000 ng/ml, adenosine deaminase 79.1 U/l. She was diagnosed as having adult-onset Still's disease. Aspirin (3.0 g/day) and prednisolone (40 mg/day) were administered. All the symptoms and laboratory data improved rapidly. Adenosine deaminase, ferritin, and LDH are considered to originate mainly from the liver. Liver injury in this disease may be a primary lesion, and various serum markers may be associated with the liver abnormalities.
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PMID:Adult-onset Still's disease: hepatic involvement and various serum markers relating to the disease activity. 192 Sep 66

Adenosine deaminase (ADA) is not only a cytosolic enzyme but can be found as an ecto-enzyme. At the plasma membrane, an adenosine deaminase binding protein (CD26, also known as dipeptidylpeptidase IV) has been identified but the functional role of this ADA/CD26 complex is unclear. Here by confocal microscopy, affinity chromatography and coprecipitation experiments we show that A1 adenosine receptor (A1R) is a second ecto-ADA binding protein. Binding of ADA to A1R increased its affinity for the ligand thus suggesting that ADA was needed for an effective coupling between A1R and heterotrimeric G proteins. This was confirmed by the fact that ASA, independently of its catalytic behaviour, enhanced the ligand-induced second messenger production via A1R. These findings demonstrate that, apart from the cleavage of adenosine, a further role of ecto-adenosine deaminase on the cell surface is to facilitate the signal transduction via A1R.
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PMID:Adenosine deaminase affects ligand-induced signalling by interacting with cell surface adenosine receptors. 860 28

The antiinflammatory action of aspirin is generally attributed to inhibition of cyclooxygenases 1 and 2, but additional mechanisms are at work. These include inhibition of NFkappaB translocation to the nucleus and the capacity of aspirin to promote accumulation of adenosine, a potent antiinflammatory autocoid. We tested these hypotheses in the murine air pouch model of acute inflammation in wild type mice and in cyclooxygenase 2 or NFkappaB knockouts. The antiinflammatory effects of aspirin, sodium salicylate and indomethacin did not correlate with inhibition of cyclooxygenase in either group. Indeed, aspirin retained its antiinflammatory properties even in COX-2 knockouts. Similarly, aspirin was no less antiinflammatory in mice rendered deficient for NFkappaB (p105) than in wild type controls. In contrast, dexamethasone lost its antiinflammatory capacity in NFkappaB knockouts. Aspirin and sodium salicylate dramatically increased concentrations of adenosine in exudates, a property shared with methotrexate and sulfasalazine. Removal of adenosine by adenosine deaminase or specific antagonism of adenosine at A(2)receptors completely reversed the antiinflammatory effects of aspirin and sodium salicylate, but not those of dexamethasone. This adenosine-dependent, antiinflammatory effect of aspirin points to another target of drug development.
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PMID:Sites of action for future therapy: an adenosine-dependent mechanism by which aspirin retains its antiinflammatory activity in cyclooxygenase-2 and NFkappaB knockout mice. 1041 67

Most of non-steroidal anti-inflammatory drugs (NSAIDs) except aspirin (ASA) produce intestinal damage in rats. In the present study, we re-examined the intestinal toxic effect of ASA in rats, in comparison with various NSAIDs, and investigated why ASA does not cause damage in the small intestine, in relation to its metabolite salicylic acid (SA). Various NSAIDs (indomethacin; 10 mg/kg; flurbiprofen; 20 mg/kg; naproxen; 40 mg/kg; dicrofenac; 40 mg/kg; ASA; 20-200 mg/kg) were administered s.c., and the small intestinal mucosa was examined macroscopically 24 h later. All NSAIDs tested, except ASA, caused hemorrhagic lesions in the small intestine, with a decrease of mucosal PGE(2) contents. ASA did not provoke any damage, despite inhibiting (prostaglandin) PG production, and prevented the occurrence of intestinal lesions induced by indomethacin, in a dose-related manner. This protective action of ASA was mimicked by the equimolar doses of SA (17.8-178 mg/kg). Indomethacin caused intestinal hypermotility, in preceding to the occurrence of lesion, and this event was followed by increases of enterobacterial translocation in the mucosa. Both ASA and SA prevented both the intestinal hypermotility and the bacterial translocation seen after indomethacin treatment. In addition, the protective effect of SA was not significantly influenced by either the adenosine deaminase or the adenosine receptor antagonists. Following administration of ASA, the blood SA levels reached a peak within 30 min and remained elevated for more than 7 h. These results suggest that SA has a cytoprotective action against indomethacin-induced small intestinal lesions, and this action may be associated with inhibition of the intestinal hypermotility and the bacterial translocation, but not mediated by endogenous adenosine. Failure of ASA to induce intestinal damage may be explained, at least partly, by a protective action of SA, the metabolite of ASA.
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PMID:Protection by aspirin of indomethacin-induced small intestinal damage in rats: mediation by salicylic acid. 1159 18

The kinetic and thermodynamic effects of aspirin and diclofenac on the activity of adenosine deaminase (ADA) were studied in 50 mM phosphate buffer pH = 7.5 at 27 and 37 degrees C, using UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). Aspirin exhibits competitive inhibition at 27 and 37 degrees C and the inhibition constants are 42.8 and 96.8 microM respectively, using spectrophotometry. Diclofenac shows competitive behavior at 27 degrees C and uncompetitive at 37 degrees C with inhibition constants of 56.4 and 30.0 microM, at respectively. The binding constant and enthalpy of binding, at 27 degrees C are 45 microM, - 64.5 kJ/mol and 61 microM, - 34.5 kJ/mol for aspirin and diclofenac. Thermodynamic data revealed that the binding process for these ADA inhibitors is enthalpy driven. QSAR studies by principal component analysis implemented in SPSS show that the large, polar, planar, and aromatic nucleoside and small, aromatic and polar non-nucleoside molecules have lower inhibition constants.
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PMID:Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac. 1784 5

Physicians recommend aspirin for prevention of heart attacks and stroke in people above the age of 40 years. In some cases, alcohol consumption accompanies aspirin intake. In this study, the in vitro effects of different doses of ethanol (50, 100, and 200 mM) and 100 microg/mL of aspirin and the possible protective role of betaine (0.5 and 1 mM) were investigated on rat cerebral synaptosomes. Synaptosomally enriched fractions, derived from Sprague Dawley rat brains, were incubated with ethanol and aspirin so as to measure sialic acid (SA), nitric oxide levels, and adenosine deaminase (ADA) activities, which are known to be the markers of alcohol damage. When combined with aspirin, ethanol increased SA levels compared with the control group at all doses, resulting in loss of SA residue from synaptosomal membrane. Betaine (0.5 mM) decreased SA levels with respect to the ethanol (200 mM) plus aspirin group (p < .05), thereby preventing SA loss. Moreover, betaine reversed the destructive effects of ethanol by elevating reduced nitric oxide levels. Aspirin, when combined with all doses of ethanol, increased ADA activity, which is crucial for purine metabolism. ADA activities were also elevated in betaine-administered groups. We propose that betaine is an effective compound in protecting the rat brain synaptosomes against ethanol and aspirin together.
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PMID:In vitro effects of ethanol with aspirin on rat brain synaptosomes: the potential protective role of betaine. 2096 55