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

---

Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal sodium handling is important for regulating BP, and renal dopamine and adenosine play an important role in renal sodium handling, however the interaction of these hormones in the kidney was not clarified. In in vivo experiments, adenosine significantly increased water and sodium excretion by 50% compared with vehicle when infused into the left renal artery, accompanied by an increase in urinary dopamine excretion in the left kidney. Neither water-sodium excretion nor dopamine excretion changed in the vehicle-infused kidney. Aromatic L-amino acid decarboxylase activity in the left kidney was significantly higher than that in the noninfused right kidney. The increase in water-sodium excretion induced by adenosine was significantly inhibited by SCH23390, a selective D1 receptor antagonist. In in vitro experiments, porcine renal proximal tubular cells were incubated with 250 microM L-dopa and N(6)-cyclohexyladenosine, an adenosine type 1 receptor agonist, after treatment with adenosine deaminase. N(6)-cyclohexyladenosine significantly increased dopamine formation at a concentration of 10(-9) to 10(-7) M, and this was completely inhibited by 1,3-dipropyl-8-cyclopentylxanthin, an adenosine A1 antagonist. These results show that renal dopamine synthesis is stimulated by adenosine through the activation of aromatic L-amino acid decarboxylase and suggest that adenosine leads to an increase in renal dopamine and natriuresis.
...
PMID:Adenosine activates aromatic L-amino acid decarboxylase activity in the kidney and increases dopamine. 1113 47

Cyclic adenosine diphosphate ribose and adenosine diphosphate ribose (ADPR) play an important role in the regulation of intracellular Ca(2+) release and K(+) channel activity in the coronary arterial smooth muscle. The role of these signaling nucleotides in the control of vascular tone has yet to be determined. The present study was designed to determine whether ADPR produces vasodilation in coronary arteries and to explore the mechanism of action of ADPR. ADPR (10-60 micromol/l) was found to produce endothelium-independent relaxation in a concentration-dependent manner in isolated and pressurized small bovine coronary arteries. The ADPR-induced vasodilation was substantially attenuated by adenosine deaminase (0.2 U/ml), and the P(1) purinoceptor antagonist 8-(p-sulfophenyl)theophylline (50 micromol/l), with maximal inhibitions of 60 and 80%, respectively. When the coronary arterial homogenates were incubated with ADPR, the production of adenosine and 5'-AMP was detected. The adenosine production was blocked by the 5'-nucleotidase inhibitor, alpha,beta-methylene adenosine 5'-diphosphate (MADP, 1 mmol/l), which was accompanied by a corresponding accumulation of 5'-AMP. This 5'-AMP accumulation was substantially inhibited by the apyrase inhibitor sodium azide (10 mmol/l). Moreover, ADPR was hydrolyzed into 5'-AMP by purified apyrase. In agreement with their inhibitory effect on the adenosine production, MADP and sodium azide significantly attenuated the vasodilator response to ADPR. The metabolism of ADPR to adenosine was only detected in cultured coronary arterial smooth muscle cells but not in endothelial cells. We concluded that ADPR produces vasodilation in small coronary arteries and that the action of ADPR is associated with the adenosine production via an apyrase- and 5'-nucleotidase-mediated metabolism.
...
PMID:Adenosine diphosphate ribose dilates bovine coronary small arteries through apyrase- and 5'-nucleotidase-mediated metabolism. 1117 96

O2 deprivation can produce many devastating clinical conditions such as myocardial infarct and stroke. The molecular mechanisms underlying the inherent tissue susceptibility or tolerance to O2 lack are, however, not well defined. Since the fruit fly, Drosophila melanogaster, is extraordinarily tolerant to O2 deprivation, we have performed a genetic screen in the Drosophila to search for loss-of-function mutants that are sensitive to low O2. Here we report on the genetic and molecular characterization of one of the genes identified from this screen, named hypnos-2. This gene encodes a Drosophila pre-mRNA adenosine deaminase (dADAR) and is expressed almost exclusively in the adult central nervous system. Disruption of the dADAR gene results in totally unedited sodium (Para), calcium (Dmca1A), and chloride (DrosGluCl-alpha) channels, a very prolonged recovery from anoxic stupor, a vulnerability to heat shock and increased O2 demands, and neuronal degeneration in aged flies. These data clearly demonstrate that, through the editing of ion channels as targets, dADAR, for which there are mammalian homologues, is essential for adaptation to altered environmental stresses such as O2 deprivation and for the prevention of premature neuronal degeneration.
...
PMID:Mutation in pre-mRNA adenosine deaminase markedly attenuates neuronal tolerance to O2 deprivation in Drosophila melanogaster. 1125 66

Kinetic and thermodynamic studies have been made on the effect of the inosine product on the activity of adenosine deaminase in a 50 mM sodium phosphate buffer, pH 7.5, at 27 degrees C using UV spectrophotometry and isothermal titration calorimetry (ITC). A competitive inhibition was observed for inosine as a product of the enzymatic reaction. A graphical-fitting method was used for determination of the binding constant and enthalpy of inhibitor binding by using isothermal titration microcalorimetry data. The dissociation-binding constant is equal to 140 microM by the microcalorimetry method, which agrees well with the value of 143 microM for the inhibition constant that was obtained from the spectroscopy method
...
PMID:A product inhibition study on adenosine deaminase by spectroscopy and calorimetry. 1229 22

In the brain, the levels of adenosine increase up to 100-fold during cerebral ischernia; however, the roles of specific cell types, enzymatic pathways and membrane transport processes in regulating intra- and extracellular concentrations of adenosine are poorly characterized. Rat primary cortical neurons and astrocytes were incubated with [(3)H]adenine for 30 min to radiolabel intracellular ATP. Cells were then treated with buffer, glucose deprivation (GD), oxygen-glucose deprivation (OGD), 100 micro M sodium cyanide (NaCN) or 500 micro M iodoacetate (IAA) for 1 h to stimulate the metabolism of ATP and cellular release of [(3)H]purines. The nucleoside transport inhibitor dipyridamole (DPR) (10 micro M), the adenosine kinase inhibitor iodotubercidin (ITU) (1 micro M), the adenosine deaminase inhibitor EHNA (1 micro M) and the purine nucleoside phosphorylase inhibitor BCX-34 (10 micro M) were tested to investigate the contribution of specific enzymes and transporters in the metabolism and release of purines from each cell type. Our results indicate that (a). under basal conditions astrocytes released significantly more [(3)H]adenine nucleotides and [(3)H]adenosine than neurons, (b). OGD, NaCN and IAA conditions produced significant increases in [(3)H]adenosine release from neurons but not astrocytes, and (c) DPR blocked [(3)H]inosine release from both astrocytes and neurons but only blocked [(3)H]adenosine release from neurons. These data suggest that, in these experimental conditions, adenosine was formed by an intracellular pathway in neurons and then released via a nucleoside transporter. In contrast, adenine nucleotide release and extracellular metabolism to adenosine appeared to predominate in astrocytes.
...
PMID:Differences between rat primary cortical neurons and astrocytes in purine release evoked by ischemic conditions. 1238 69

Effects of Ap4A and NAD--precursor of adenosine, on renal plasma flow (RPF), glomerular filtration rate (GFR) and urine excretion were determined in the anaesthetised rats. Infusion of Ap4A or NAD (i.v., bolus--1 micromol/kg followed by 10 nmol/min/kg) decreased RPF and GFR (by 30 and 40%, respectively). In spite of GFR reduction during Ap4A infusion, the significant increase in sodium excretion and urine flow was noticed: fractional sodium (FENa) and urine excretion (FEurine) rose 15-fold and 2.5-fold in comparison with the control value, respectively. In contrast to Ap4A, NAD-induced decrease in GFR was associated with parallel decrease in sodium and urine excretion, thus the FENa and FEurine did not significantly change. Pretreatment with adenosine deaminase (adenosine degrading enzyme, 2 U/min/kg) or theophylline (P1-receptors antagonist, 0.2 mmol/min/kg) ceased responses to NAD, whereas Ap4A-induced changes were not affected. Pre-treatment with suramin (P2-receptors antagonist, (i.v., bolus--12 mg/kg followed by 1.2 mg/min/kg) completely abolished the renal effects of Ap4A. We conclude that Ap4A may exert specific action on renal function. It acts different from NAD that modified renal function through its hydrolysis product--adenosine. Ap4A might reduce glomerular filtration rate and evoke natriuresis and diuresis, and its effects are probably mediated through stimulation of P2-receptors.
...
PMID:Renal haemodynamics and natriuretic responses to intravenous administration of diadenosine tetraphosphate (Ap4A) and nicotinamide adenine dinucleotide (NAD) in rat. 1283 19

Kinetic and thermodynamic studies were made on the effect of caffeine on the activity of adenosine deaminase in 50 mM sodium phosphate buffer, pH 7.5, using UV spectrophotometry and isothermal titration calorimetry (ITC). An uncompetitive inhibition was observed for caffeine. A graphical fitting method was used for determination of binding constant and enthalpy of inhibitor binding by using isothermal titration microcalorimetry data. The dissociation-binding constant is equal to 350 microM by the microcalorimetry method, which agrees well with the value of 342 microM for the inhibition constant that was obtained from the spectroscopy method. Positive dependence of caffeine binding on temperature indicates a hydrophobic interaction.
...
PMID:Inhibition study of adenosine deaminase by caffeine using spectroscopy and isothermal titration calorimetry. 1451 65

A facile synthesis of oligodeoxynucleotides (ODN) containing 2'-deoxy-6-thioinosine (dI6S) based on the convertible nucleoside O6-phenyl-2'-deoxyinosine is presented. After standard solid-phase DNA synthesis and removal of the cyanoethyl protecting groups with DBU treatment with aqueous sodium hydrogen sulfide introduces the sulfur functionality, deprotects the other nucleobases and cleaves the ODN from the solid support in a one-pot reaction. In addition, the extinction coefficient of 2'-deoxy-6-thioinosine is determined by enzymatic fragmentation of the resulting ODN in the presence of adenosine deaminase.
...
PMID:Convenient synthesis of oligodeoxynucleotides containing 2'-deoxy-6-thioinosine. 1456 42

To evaluate if endogenous extracellular adenosine influences sodium channel activity in nerve terminals, we investigated how manipulations of extracellular adenosine levels influence 22Na uptake by rat brain synaptosomes stimulated with veratridine (VT). To decrease extracellular adenosine levels, adenosine deaminase (ADA) that converts adenosine into an inactive metabolite was used. To increase extracellular adenosine levels, we used the adenosine deaminase inhibitor erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), as well as the inhibitor of adenosine transport, nitrobenzylthioinosine (NBTI). ADA (0.1-5 U/ml) caused an excitatory effect on 22Na uptake stimulated by veratridine, which was abolished in the presence of the adenosine deaminase inhibitor erythro-9(2-hydroxy-3-nonyl) adenine (EHNA, 25 microM). Both the adenosine uptake inhibitor nitrobenzylthioinosine (NBTI, 1-10 microM) and the adenosine deaminase inhibitor EHNA (10-25 microM) inhibited 22Na uptake by rat brain synaptosomes. It is suggested that adenosine is tonically inhibiting sodium uptake by rat brain synaptosomes.
...
PMID:Endogenous adenosine modulation of 22Na uptake by rat brain synaptosomes. 1457 Apr 5

The kinetic parameters of adenosine deaminase such as Km and Ki were determined in the absence and presence of adenine derivatives (R1-R24) in sodium phosphate buffer (50 mM; pH 7.5) solution at 27 degrees C. These kinetic parameters were used for QSAR analysis. As such, we found some theoretical descriptors to which the binding affinity of adenosine deaminase (ADA) towards several adenine nucleosides as inhibitors is correlated. QSAR analysis has revealed that binding affinity of the adenine nucleosides upon interaction with ADA depends on the molecular volume, dipole moment of the molecule, electric charge around the N1 atom, and the highest of positive charge for the related molecules.
...
PMID:QSAR analysis for ADA upon interaction with a series of adenine derivatives as inhibitors. 1511 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---