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 effects of 5-amino-4-imidazolecarboxamide riboside (rAICA) on coronary adenosine efflux were examined in blood-free perfused working rat heart preparations subjected to mild (70% O2) and severe hypoxia (45% O2). Under these hypoxic conditions, no significant increase of coronary adenosine effluxes was observed in the presence of 300 microM rAICA alone. However, rAICA-induced augmentation of coronary adenosine efflux during hypoxia was revealed in the presence of an adenosine deaminase inhibitor, erythro-(2-hydroxy-3-nonyl)adenine hydrochloride, indicating that the failure to note the increase in coronary adenosine efflux was due to a rapid deamination of adenosine to inosine. A depression in heart rate during mild and severe hypoxia was significantly exacerbated by rAICA. These effects on heart rate were mediated by adenosine, since they were effectively blocked by 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine, a selective adenosine A1-receptor antagonist. These results suggest that rAICA elevates adenosine efflux during hypoxia.
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PMID:5-Amino-4-imidazolecarboxamide riboside raises adenosine in perfused hypoxic rat heart. 180 58

In summary, intermittent, low dose methotrexate treatment is: 1.) antiinflammatory in the murine air pouch model of inflammation; 2.) selectively increases intracellular AICAR concentration; 3.) increases adenosine concentration in an inflammatory exudate; and, 4.) inhibits leukocyte accumulation at an inflamed site by a mechanism that is specifically reversed by adenosine deaminase and the adenosine A2 receptor antagonist DMPX but not the A1 antagonist DPCPX. In conclusion, we have demonstrated a novel mechanism for the antiinflammatory action of methotrexate; methotrexate is a nonsteroidal antiinflammatory agent that acts by promoting the release of adenosine which engages A2 receptors on inflammatory cells.
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PMID:The antiinflammatory effects of methotrexate are mediated by adenosine. 766 Sep 40

Endogenous extracellular adenosine provides some protection against excitotoxicity in the central nervous system, but it appears to be incomplete. Potentiating the formation of extracellular adenosine that occurs when excitatory amino acid receptors are activated might provide additional protection. We studied the effects of AICAR (AICA riboside, acadesine) and of inhibitors of adenosine metabolism on the release of adenosine from rat cortical slices. AICAR had no effects on basal N-methyl-D-aspartate (NMDA)- or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid (AMPA)-evoked adenosine release, but it increased kainate-evoked adenosine release 1.4-fold. This selective action of AICAR may make it useful for treating kainate receptor-mediated excitotoxicity. Inhibition of adenosine kinase with either 20 microM 5'-amino-5'-deoxyadenosine or 5'-iodotubercidin had a much greater effect on excitatory amino acid-evoked adenosine release than on basal adenosine release. Inhibition of adenosine kinase increased excitatory amino acid-evoked adenosine release 3-7-fold whereas inhibition of adenosine deaminase only increased evoked adenosine release 2-2.5-fold. Finally, 0.2 microM 5'-iodotubercidin and 200 microM 2'-deoxycoformycin caused similar increases in the basal rates of extracellular adenosine formation, but 5'-iodotubercidin produced over twice as much potentiation of the rate of NMDA-evoked adenosine formation than did 2'-deoxycoformycin. These findings suggest that adenosine kinase inhibitors may produce an event-specific potentiation of evoked adenosine formation, i.e. more effect on evoked formation than on basal formation. If so, adenosine kinase inhibitors may prove useful for preventing/treating diseases associated with excessive excitation in the brain, such as seizures, excitotoxicity and neurodegeneration.
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PMID:Potentiation of excitatory amino acid-evoked adenosine release from rat cortex by inhibitors of adenosine kinase and adenosine deaminase and by acadesine. 880 8

Cyclic adenosine monophosphate (cAMP) has been implicated as an important regulator of meiotic maturation in mammalian oocytes. A decrease in cAMP, brought about by the action of cAMP phosphodiesterase (PDE), is thought to initiate germinal vesicle breakdown (GVB) by the inactivation of cAMP-dependent protein kinase. However, the product of PDE activity, 5'-AMP, is a potent activator of an important regulatory enzyme, AMP-activated protein kinase (AMPK). The aim of this study was to evaluate a possible role for AMPK in meiotic induction, using oocytes obtained from eCG-primed, immature mice. Alpha-1 and -2 isoforms of the catalytic subunit of AMPK were detected in both oocytes and cumulus cells. When 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICA riboside), an activator of AMPK, was tested on denuded oocytes (DO) and cumulus cell-enclosed oocytes (CEO) maintained in meiotic arrest by dbcAMP or hypoxanthine, GVB was dose-dependently induced. Meiotic induction by AICA riboside in dbcAMP-supplemented medium was initiated within 3 h in DO and 4 h in CEO and was accompanied by increased AMPK activity in the oocyte. AICA riboside also triggered GVB when meiotic arrest was maintained with hypoxanthine, 8-AHA-cAMP, guanosine, or milrinone, but was ineffective in olomoucine- or roscovitine-arrested oocytes, indicating that it acts upstream of maturation-promoting factor. Adenosine monophosphate dose-dependently stimulated GVB in DO when meiotic arrest was maintained with dbcAMP or hypoxanthine. This effect was not mimicked by other monophosphate or adenosine nucleotides and was not affected by inhibitors of ectophosphatases. Combined treatment with adenosine and deoxycoformycin, an adenosine deaminase inhibitor, stimulated GVB in dbcAMP-arrested CEO, suggesting AMPK activation due to AMP accumulation. It is concluded that phosphodiesterase-generated AMP may serve as a transducer of the meiotic induction process through activation of AMPK.
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PMID:A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. 1196 66

5-Aminoimidazole-4-carboxamide riboside (AICA riboside; Acadesine) activates AMP-activated protein kinase (AMPK) in intact cells, and is reported to exert protective effects in the mammalian CNS. In rat cerebrocortical brain slices, AMPK was activated by metabolic stress (ischaemia > hypoxia > aglycaemia) and AICA riboside (0.1-10 mm). Activation of AMPK by AICA riboside was greatly attenuated by inhibitors of equilibrative nucleoside transport. AICA riboside also depressed excitatory synaptic transmission in area CA1 of the rat hippocampus, which was prevented by an adenosine A1 receptor antagonist and reversed by application of adenosine deaminase. However, AICA riboside was neither a substrate for adenosine deaminase nor an agonist at adenosine receptors. We conclude that metabolic stress and AICA riboside both stimulate AMPK activity in mammalian brain, but that AICA riboside has an additional effect, i.e. competition with adenosine for uptake by the nucleoside transporter. This results in an increase in extracellular adenosine and subsequent activation of adenosine receptors. Neuroprotection by AICA riboside could be mediated by this mechanism as well as, or instead of, by AMPK activation. Caution should therefore be exercised in ascribing an effect of AICA riboside to AMPK activation, especially in systems where inhibition of adenosine re-uptake has physiological consequences.
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PMID:AICA riboside both activates AMP-activated protein kinase and competes with adenosine for the nucleoside transporter in the CA1 region of the rat hippocampus. 1500 83

Adenosine has been shown to initiate apoptosis through different mechanisms: (i) activation of adenosine receptors, (ii) intracellular conversion to AMP and stimulation of AMP-activated kinase, (iii) conversion to S-adenosylhomocysteine (AdoHcy), which is an inhibitor of S-adenosylmethionine (AdoMet)-dependent methyltransferases. Since the pathways involved are still not completely understood, we further investigated the role of AdoHcy hydrolase in adenosine-induced apoptosis. In HepG2 cells, adenosine induced caspase-like activity and DNA fragmentation, a marker of apoptosis. These effects were potentiated by co-incubation with homocysteine or adenosine deaminase inhibitor, pentostatin, and were mimicked by inhibition of AdoHcy hydrolase by adenosine-2',3'-dialdehyde (Adox). Adenosine-induced effects were significantly inhibited by dipyridamole, an inhibitor of adenosine transporter, whereas inhibitors of adenosine kinase did not affect adenosine-induced changes. Various adenosine receptor agonists and AICAR, an activator of AMP-activated kinase, did not mimic the effect of adenosine. Thus, adenosine-induced apoptosis is likely due to intracellular action of AdoHcy and independent of AMP-activated kinase and adenosine receptors. Because elevated AdoHcy levels are associated with reduced mRNA methylation, we studied mRNA expression in Adox-treated cells by microarray analysis. Since several p53-target genes and other apoptosis-related genes were up-regulated by Adox, we conclude that AdoHcy is involved in adenosine-induced apoptosis by altering gene expression.
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PMID:Role of S-adenosylhomocysteine hydrolase in adenosine-induced apoptosis in HepG2 cells. 1709 37