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)

The mammalian RNA-specific adenosine deaminases DRADA/dsRAD (alias ADAR) and RED1 (alias ADARB1) have been implicated in the site-selective editing of brain-expressed pre-mRNAs for glutamate receptor subunits and of antigenomic RNA of hepatitis delta virus. These enzymes are expressed in many if not all tissues, predicting an as yet unappreciated significance for adenosine deamination-mediated recoding of gene transcripts in the mammalian organism. We now report the molecular cloning of cDNA for RED2 (alias ADARB2), a third member of the RNA-specific adenosine deaminase family in the rodent. RED2 is closely sequence-related to RED1 but appears to be expressed only in the brain, where expression is widespread reaching highest levels in olfactory bulb and thalamus. RED2 further differs from RED1 in having a 54-residue amino-terminal extension which includes an arginine-rich motif. Different from DRADA and RED1, recombinantly expressed RED2 did not deaminate adenosines in extended synthetic dsRNA or in GluR-B pre-mRNA. However, a chimera of RED1 and RED2 edited the GluR-B Q/R and R/G sites with moderate efficiency. Our data suggest that RED2 may edit brain-specific transcripts with distinct structural features.
...
PMID:RED2, a brain-specific member of the RNA-specific adenosine deaminase family. 894 18

Topical application of ethanol to the gastrointestinal mucosa induces vasodilation. Using an in vivo microscopy technique, we studied the effect of topical ethanol on the submucosal microvessels that control mucosal blood flow in the rat stomach and identified vasoactive substances and receptors that mediate the ethanol vasoaction. Topical ethanol (1-20%) dilated submucosal arterioles dose dependently, but did not change venular diameters. An inhibitor of alcohol dehydrogenase, 1 mM 4-methylpyrazole, did not alter the ethanol vasoaction. Ethanol-induced arteriolar dilation was eliminated by adenosine deaminase, but other vasodilator inhibitors such as atropine, pyrilamine, indomethacin, human calcitonin gene-related peptide-(8-37), and N omega-nitro-L-arginine methyl ester did not prevent it. Ethanol-induced arteriolar dilation was inhibited by an adenosine A2-receptor antagonist, but not by an A1-receptor antagonist, whereas an A2-agonist, but not an A1-agonist, dose dependently dilated arterioles. Exogenous adenosine (10(-5)-10(-3) M) dilated arterioles to a similar extent as ethanol. This response was inhibited by an A2-antagonist. We conclude that nonmetabolized ethanol increases gastric mucosal blood flow via A2-receptors in submucosal arterioles.
...
PMID:Adenosine A2-receptor mediates ethanol-induced arteriolar dilation in rat stomach. 899 46

In the perfused guinea-pig heart reactive hyperaemia (RH) after occlusion of coronary flow (1-60 s) was inhibited by 100-60% with NG-nitro-L-arginine (100 microM) and to a lesser extent (by 35%) after 8-phenyltheophylline (10 microM), but not by indomethacin (5 microM). Inhibition of adenosine deaminase by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) (5 microM) not only increased the concentration of adenosine in the coronary perfusate, but also prolonged the duration of RH. RH induced cardiac generation of prostacyclin, nitric oxide and adenosine as indicated by the appearance of 6-keto-PGF1 alpha, cyclic GMP, adenosine, inosine, hypoxanthine, xanthine and urate in the perfusate. Only NO and adenosine, but not prostacyclin, were responsible for RH. RH after short-term (1-10 s) coronary occlusion was mediated by NO, whereas adenosine and NO maintained RH that followed after longer (20 s-10 min) periods of cardiac ischaemia. Prostacyclin never participated in the mediation of RH.
...
PMID:Ischaemic cardiac hyperaemia: role of nitric oxide and other mediators. 908 46

The metabolites that mediate coronary reactive hyperemia have not been definitely identified. Although adenosine and endothelium derived substances seem to be involved, their relative contributions have not been defined yet. In the canine coronary circulation, we studied the relative participation of adenosine, nitric oxide and prostacyclin in reactive hyperemia, by measuring the changes produced by interfering with the synthesis or action of these metabolites. The dose-response curve for flow changes vs intracoronary administration of adenosine was displaced to the right after the inhibition of nitric oxide synthesis with N-omega-nitro-L-arginine, revealing that nitric oxide release partly mediates the vasodilator action of adenosine. The inhibition of PGI-2 synthesis with indomethacin did not modify reactive hyperemia. Interference with adenosine action, by administration of adenosine deaminase plus theophylline, decreased reactive hyperemia by 31.0 +/- 4.0% (p < 0.001). Inhibition of nitric oxide synthesis decreased reactive hyperemia by a larger (p < 0.005) magnitude, 41.0 +/- 3.9% (p < 0.001), revealing the existence of other stimuli for nitric oxide release in reactive hyperemia besides adenosine. Simultaneous inhibition of nitric oxide and PGI-2 syntheses and of adenosine action reduced reactive hyperemia, but the effect was not additive, reaching 49.5 +/- 4.5% of control. Since nitric oxide and adenosine are the most important mediators in reactive hyperemia so far described, our results suggest that other metabolites, acting directly or through mediators other than adenosine or nitric oxide, are responsible for about 50% of coronary reactive hyperemia.
...
PMID:Relative participation of adenosine and endothelium derived mediators in coronary reactive hyperemia in the dog. 925 46

The purpose of the present study was to examine mechanisms of activity-dependent changes of cerebral blood flow (CBF) in rat cerebellar cortex by laser-Doppler flowmetry, using two synaptic inputs that excite different regions of the same target cell and with different synaptic strength. The apical part of Purkinje cells was activated by electrical stimulation of parallel fibers, whereas the cell soma and the proximal part of the dendritic tree were activated by climbing fibers using harmaline (40 mg/kg ip) or electrical stimulation of the inferior olive. Glass microelectrodes were used for recordings of field potentials and single-unit activity of Purkinje cells. CBF increases evoked by parallel fibers were most pronounced in the upper cortical layers. In contrast, climbing fiber stimulation increased CBF in the entire cortex. Inhibition of nitric oxide (NO) synthase activity by NG-nitro-L-arginine (L-NNA) or guanylate cyclase activity by 1H-[1,2,4(oxadiazolo)4,3-a]quinoxaline-1-one did not affect basal or harmaline-induced Purkinje cell activity but attenuated harmaline- and parallel fiber-evoked CBF increases by approximately 40-50%. Application of 8-(p-sulfophenyl)theophylline and adenosine deaminase reduced the harmaline-evoked CBF increase without any effect on the parallel fiber-evoked CBF response. The results suggest that CBF increases elicited by activation of Purkinje cells are partially mediated by the NO-guanosine 3',5'-cyclic monophosphate system independent of the input function but that adenosine contributes as well when climbing fibers are activated. This is the first demonstration of variations of coupling as a function of postsynaptic activity in the same cell.
...
PMID:Laminar analysis of activity-dependent increases of CBF in rat cerebellar cortex: dependence on synaptic strength. 932 3

Members of the double-stranded RNA- (dsRNA) specific adenosine deaminase gene family convert adenosine residues into inosines in dsRNA and are involved in A-to-I RNA editing of transcripts of glutamate receptor (GluR) subunits and serotonin receptor subtype 2C (5-HT(2C)R). We have isolated hADAR3, the third member of this class of human enzyme and investigated its editing site selectivity using in vitro RNA editing assay systems. As originally reported for rat ADAR3 or RED2, purified ADAR3 proteins could not edit GluR-B RNA at the "Q/R" site, the "R/G" site, and the intronic "hot spot" site. In addition, ADAR3 did not edit any of five sites discovered recently within the intracellular loop II region of 5-HT(2C)R RNAs, confirming its total lack of editing activity for currently known substrate RNAs. Filter-binding analyses revealed that ADAR3 is capable of binding not only to dsRNA but also to single-stranded RNA (ssRNA). Deletion mutagenesis identified a region rich in arginine residues located in the N-terminus that is responsible for binding of ADAR3 to ssRNA. The presence of this ssRNA-binding domain as well as its expression in restricted brain regions and postmitotic neurons make ADAR3 distinct from the other two ADAR gene family members, editing competent ADAR1 and ADAR2. ADAR3 inhibited in vitro the activities of RNA editing enzymes of the ADAR gene family, raising the possibility of a regulatory role in RNA editing.
...
PMID:A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. 1083 96

Human adenosine deaminase (ADA) occurs as a 41-kDa soluble monomer in all cells. On epithelia and lymphoid cells of humans, but not mice, ADA also occurs bound to the membrane glycoprotein CD26/dipeptidyl peptidase IV. This "ecto-ADA" has been postulated to regulate extracellular Ado levels, and also the function of CD26 as a co-stimulator of activated T cells. The CD26-binding site of human ADA has been localized by homolog scanning to the peripheral alpha2-helix (amino acids 126-143). Among the 5 non-conserved residues within this segment, Arg-142 in human and Gln-142 in mouse ADA largely determined the capacity for stable binding to CD26 (Richard, E., Arredondo-Vega, F. X., Santisteban, I., Kelly, S. J., Patel, D. D., and Hershfield, M. S. (2000) J. Exp. Med. 192, 1223-1235). We have now mutagenized conserved alpha2-helix residues in human and mouse ADA and used surface plasmon resonance to evaluate binding kinetics to immobilized rabbit CD26. In addition to Arg-142, we found that Glu-139 and Asp-143 of human ADA are also important for CD26 binding. Mutating these residues to alanine increased dissociation rates 6-11-fold and the apparent dissociation constant K(D) for wild type human ADA from 17 to 112-160 nm, changing binding free energy by 1.1-1.3 kcal/mol. This cluster of 3 charged residues appears to be a "functional epitope" that accounts for about half of the difference between human and mouse ADA in free energy of binding to CD26.
...
PMID:Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV. 1190 Nov 52

The bacterial tRNA adenosine deaminase (TadA) generates inosine by deaminating the adenosine residue at the wobble position of tRNA(Arg-2). This modification is essential for the decoding system. In this study, we determined the crystal structure of Aquifex aeolicus TadA at a 1.8-A resolution. This is the first structure of a deaminase acting on tRNA. A. aeolicus TadA has an alpha/beta/alpha three-layered fold and forms a homodimer. The A. aeolicus TadA dimeric structure is completely different from the tetrameric structure of yeast CDD1, which deaminates mRNA and cytidine, but is similar to the dimeric structure of yeast cytosine deaminase. However, in the A. aeolicus TadA structure, the shapes of the C-terminal helix and the regions between the beta4 and beta5 strands are quite distinct from those of yeast cytosine deaminase and a large cavity is produced. This cavity contains many conserved amino acid residues that are likely to be involved in either catalysis or tRNA binding. We made a docking model of TadA with the tRNA anticodon stem loop.
...
PMID:Crystal structure of tRNA adenosine deaminase (TadA) from Aquifex aeolicus. 1567 68

A-to-I pre-mRNA editing by adenosine deaminase enzymes has been reported to enhance protein diversity in the nervous system. In Drosophila, the resistance to dieldrin (RDL) gamma-aminobutyric acid (GABA) receptor subunit displays an editing site (R122) that is close to the putative GABA-binding site. We assessed the functional effects of editing at this site by expressing homomeric RDL receptors in Xenopus oocytes. After replacement of arginine 122 with a glycine, both agonist and fipronil potencies were shifted to the right in either fipronil-sensitive receptors or mutated resistant receptors (A301G/T350M). These data provide the first insight on the influence of RNA editing on GABA receptor function.
...
PMID:RNA editing regulates insect gamma-aminobutyric acid receptor function and insecticide sensitivity. 1852 Sep 97

Experimental evidence in animal models suggests that adenosine is involved in the regulation of digestive functions. This study examines the influence of adenosine on the contractile activity of human colon. Reverse transcription-polymerase chain reaction revealed A(1) and A(2a) receptor expression in colonic neuromuscular layers. Circular muscle preparations were connected to isotonic transducers to determine the effects of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A(1) receptor antagonist), ZM 241385 (A(2a) receptor antagonist), CCPA (A(1) receptor agonist) and 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamide-adenosine (CGS 21680; A(2a) receptor agonist) on motor responses evoked by electrical stimulation or carbachol. Electrically evoked contractions were enhanced by DPCPX and ZM 241385, and reduced by CCPA and CGS 21680. Similar effects were observed when colonic preparations were incubated with guanethidine (noradrenergic blocker), L-732,138, GR-159897 and SB-218795 (NK receptor antagonists). However, in the presence of guanethidine, NK receptor antagonists and N(omega)-propyl-L-arginine (NPA; neuronal nitric oxide synthase inhibitor), the effects of DPCPX and CCPA were still evident, while those of ZM 241385 and CGS 21680 no longer occurred. Carbachol-induced contractions were unaffected by A(2a) receptor ligands, but they were enhanced or reduced by DPCPX and CCPA, respectively. When colonic preparations were incubated with guanethidine, NK antagonists and atropine, electrically induced relaxations were partly reduced by ZM 241385 or NPA, but unaffected by DPCPX. Dipyridamole or application of exogenous adenosine reduced electrically and carbachol-evoked contractions, whereas adenosine deaminase enhanced such motor responses. In conclusion, adenosine exerts an inhibitory control on human colonic motility. A(1) receptors mediate direct modulating actions on smooth muscle, whereas A(2a) receptors operate through inhibitory nitrergic nerve pathways.
...
PMID:A1 and A2a receptors mediate inhibitory effects of adenosine on the motor activity of human colon. 1901 12


<< Previous 1 2 3 4 5 6 Next >>

---