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)

Findings in peripheral tissues that diadenosine polyphosphates (Ap(n)As) activate 5'-nucleotidase activity and inhibit adenosine kinase activity in vitro led us to test the hypothesis that Ap(n)As and analogues thereof, through such actions on purine enzymes, increase brain levels of endogenous adenosine in vivo. Accordingly, we tested Ap(n)As for their effects on the in vitro activities of adenosine kinase, adenosine deaminase, AMP deaminase and 5'-nucleotidase and, following unilateral microinjections in rat striatum, on in vivo levels of endogenous adenosine. Adenosine kinase activity was not affected significantly by 5',5'''-P1,P2-diadenosine pyrophosphate (Ap2A) or by 5',5'''-P1,P3-diadenosine triphosphate (Ap3A), but was inhibited by 5',5'''-P1,P4-diadenosine tetraphosphate (Ap4A), 5',5'''-P1,P5-diadenosine pentaphosphate (Ap5A) and 5',5'''-P1,P6-diadenosine hexaphosphate (Ap6A); apparent IC50 values were 5.0, 3.3 and 500 microM, respectively. Inhibition of adenosine kinase activity by Ap4A and the four metabolically stable analogues of Ap4A tested was uncompetitive. Following unilateral intrastriatal injections, adenosine levels, relative to uninjected contralateral striatum, were decreased significantly (P < 0.05) by 48% with Ap4A and by 37% with AppCH2ppA, a metabolically stable analogue of Ap4A. Striatal levels of adenosine were not affected significantly by Ap5A or Ap6A. Cytosolic, but not particulate 5'-nucleotidase activity was inhibited and AMP deaminase activity was increased by some Ap(n)As. Although adenosine kinase inhibitors increase levels of endogenous adenosine and we showed here that Ap(n)As were potent inhibitors of this enzyme, these particular actions of Ap(n)As were not consistent with their effects on levels of endogenous adenosine.
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PMID:Diadenosine polyphosphates inhibit adenosine kinase activity but decrease levels of endogenous adenosine in rat brain. 929 23

Slices of rat hippocampus can be induces to generate spontaneous interictal-like bursts of action potentials when perfused with a with a medium containing no added magnesium and 4-aminopyridine (4AP). The frequency of these bursts is depressed by adenosine 5'triphosphate (ATP) and this effect can be prevented by cyclopentyltheophylline but not by adenosine deaminase. AMP (50 microM) had a similar action to reduce discharge rate. At 10 microM, adenosine, diadenosine tetraphosphate and diadenosine pentaphosphate all decreased the burst frequency. Adenosine deaminase (0.2 U ml-1) totally annulled the inhibition of epileptiform activity produced by 10 microM adenosine but reduced only the later components of the inhibition by 10 microM diadenosine tetraphosphate and diadenosine pentaphosphate. Cyclopentyltheophylline prevented the depression of burst discharges by diadenosine tetraphosphate. 5'-adenylic acid deaminase (AMPPase) did not significantly alter the discharge rate over the 10 min superfusion period used for drum application but did prevent the depressant effect of AMP and ATP. AMP deaminase did not prevent the inhibitory effects of diadenosine tetraphosphate. The results suggests that in the CA3 region of the hippocampus, diadenosine tertraphosphate and diadenosine pentaphosphate act partly by stimulating xanthine sensitive receptors directly and partly via metabolism to adenosine, and that AMP may be responsible for the inhibitory effects of ATP on epileptiform activity.
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PMID:Nucleotide and dinucleotide effects on rates of paroxysmal depolarising bursts in rat hippocampus. 1055 Oct 2

The activation of P2-receptors has a wide range of diverse effects in many tissues. Here we show that extracellular ATP stimulates lipogenesis in adipocytes derived from the epididymal fat pads of male Wistar rats. The lipogenic effect of ATP is not susceptible to treatment of adipocytes with adenosine deaminase or an adenosine receptor antagonist. Degradation of ATP in adipocyte suspension by ectonucleotidases is slow and remaining ATP concentrations are sufficient to activate P2-receptors. ATP does not affect basal or insulin stimulated glucose transport, or basal or isoproterenol stimulated lipolysis, respectively. The lipogenic effect of ATP is mimicked by the adenine compounds, ADP, AMP, and beta,gamma-methylene-ATP, but not by other nucleotides (UTP, UDP, CTP, GTP, ITP, and diadenosine tetraphosphate), indicating that extracellular nucleotides stimulate lipogenesis via a P2-receptor. ATP and its receptor may define a signalling system in adipocytes, which regulates fat stores independently from established hormones.
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PMID:Stimulation of lipogenesis in rat adipocytes by ATP, a ligand for P2-receptors. 1535 93