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

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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)

Specific sensitive rabbit antisera directed against the adenosine derivative laevulinic acid (O2',3'-adenosine acetal), which are capable of detecting as little as 1 pmol of adenosine by radioimmunoassay and which require more than 1000- to 40,000-fold greater concentrations of adenine nucleotides to displace adenosine binding to antisera, have been developed. These antisera were employed to localize adenosine immunoreactivity throughout the rat CNS using the peroxidase-antiperoxidase (PAP) complex and avidin-biotin-peroxidase complex (ABC) immunocytochemical techniques. Intense staining for adenosine immunoreactivity was localized to the cytoplasm of perikarya and fibers in neuronal cell groups of discrete rat brain regions. Areas containing highest levels of immunoreactivity included the pyramidal cells of the hippocampus, the granule cells of the dentate gyrus, subnuclei of the thalamus, amygdala, and hypothalamus, the primary olfactory cortex, and many motor and sensory nuclei of the brain stem and spinal cord. High levels also occurred in certain layers of the cerebral cortex, the caudate-putamen, the septal nuclei, and the Purkinje cell layer of the cerebellum. Varying the extent of tissue hypoxia altered only the levels of endogenous immunoreactive adenosine without changing the pattern of distribution of the immunoreactivity. Staining was abolished by immunoabsorption and by pretreatment of tissue sections with adenosine deaminase. The localization of adenosine to discrete neuronal groups in the brain supports the possibility of a neurotransmitter or neuromodulatory role for adenosine.
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PMID:Adenosine-containing neurons in the brain localized by immunocytochemistry. 242 24

The development, distribution and olfactory bulb projections of neurons immunoreactive for the enzyme adenosine deaminase (ADA) were studied in olfactory systems of embryonic, early postnatal and young adult rats. On embryonic day (E) 12, ADA-immunoreactivity first appeared in the placode of the olfactory epithelium. On E15, ADA-immunoreactive olfactory receptor and precursor cells gave rise to immunostained axons projecting to the olfactory bulb. Numerous immunostained glomeruli were observed on postnatal day (P) 1. After P25, immunoreactivity within receptor cells and glomeruli decreased. In prenatal and early postnatal animals, ADA-immunoreactive neurons were observed in the anterior olfactory nucleus (AON), dorsal transition area, ventral taenia tecta, primary olfactory cortex (POC), entorhinal cortex and ventral agranular insular cortex. After P25 to P30, these neurons lost their immunoreactivity, except those in the medial AON where light immunostaining persisted. In contrast, ADA-immunostaining of neurons in the horizontal limb of the diagonal band (HDB) and olfactory tubercle increased throughout development. About 70 to 75% of the ADA-immunoreactive neurons in the AON, a small number of those in the POC and about 75% of the ADA-immunoreactive non-cholinergic neurons in the HDB were found to project to the olfactory bulb. The functions of ADA in the olfactory system may be related to the precocious development of, and/or purinergic neurotransmission within, this system.
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PMID:Adenosine deaminase-containing neurons in the olfactory system of the rat during development. 330 Aug 65

Antisera against rat-liver S-adenosylhomocysteine hydrolase (SAH-hydrolase) and calf intestinal mucosal adenosine deaminase (ADA) were raised in rabbits and subsequently used to determine the distribution of the corresponding enzymes in rat-brain using the peroxidase-antiperoxidase immunohistochemical procedure. SAH-hydrolase antigenicity was prominent in the neocortex, hippocampal formation, cerebellum and olfactory tubercle. In the cerebellum, only those cells associated with the Purkinje layer possessed pronounced reactivity with anti-SAH hydrolase. The intense staining present could be correlated mainly with nuclei, the cytosol being stained less intensely. Weak ADA antigenicity was found throughout the brain, but strong antigenic reactivity was associated with neurones in the basal hypothalamus, superior colliculus and in nerve fibres in many regions. Many ADA antigenic neurones and fibres were seen in close proximity to blood vessels. The distribution of ADA antigenicity was also studied in cat and rabbit brain. In cat brain only general staining of tissue occurred with anti-ADA and no intensely stained regions comparable to those seen in rat brain were observed. Rabbit brain showed weak specifically stained neurones only in the superior colliculus. Enzyme assays were also performed to confirm immunohistochemical findings. There appears to be little in common between regions which stained intensely with anti-SAH hydrolase and anti-ADA respectively. The possible implications of these findings are discussed.
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PMID:Localization of S-adenosylhomocysteine hydrolase and adenosine deaminase immunoreactivities in rat brain. 351 60

The activity of adenosine deaminase (ADA) was determined in whole brain of rats at the embryonic age of 15 days through to adulthood and in nine brain regions in rats 1 day old through to adulthood. In 1-day-old rats, the highest activity was seen in olfactory bulbs (550 +/- 15 nmol/mg protein/30 min) and this was 4.5-fold higher than that in the pons, which was the lowest. In adult animals, olfactory bulb still contained the greatest activity, which was about eightfold higher than hippocampus, which had the lowest. Except for hypothalamus, where ADA activity increased nearly twofold in rats between the ages of 1 and 50 days, significant decreases of as much as fivefold were found in whole brain, superior colliculus, cortex, hippocampus, cerebellum, olfactory bulbs, and olfactory nucleus. In contrast, ADA activity in pons and subcortex remained relatively constant throughout the developmental period. The Km values for ADA in whole brain at 18 days gestation (48 +/- 5 microM) were not significantly different from that observed in adult rats (38 +/- 7 microM), whereas the Vmax values decreased significantly from 339 +/- 9 to 108 +/- 8 nmol/mg protein/30 min. Taken together, the developmental patterns observed in the various brain regions appear not to correspond to any one particular process such as periods of rapid cell proliferation, cell death, synaptogenesis, or myelination. Nor do they correspond to known developmental profiles of transmitters, their receptors, or their metabolic enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ontogenesis of adenosine deaminase activity in rat brain. 379 95

It has previously been demonstrated that neurons immunoreactive for the enzyme adenosine deaminase (ADA) have a highly restricted distribution pattern in the adult rat brain. In order to determine whether the pattern of ADA expression is equally limited during the period of brain development, the localization of ADA was investigated immunohistochemically in brains of embryonic, early postnatal and young adult rats. No immunostaining for ADA was detected on the 12th embryonic day. On embryonic day 15, ADA-immunoreactive cells were first observed in the hypoglossal motor nucleus, and on day 18 in cingulate, retrosplenial and visual cortex, in the posterior basal hypothalamus, and in the facial motor nucleus. On the 20th embryonic day ADA-immunoreactive neurons appeared in various olfactory and related systems and in the superior colliculus. On the 1st postnatal day, immunoreactivity was intensified in all structures in which it was observed at preceeding ages and, in addition, appeared in several brainstem regions. On postnatal day 10 and 15, immunostained neurons appeared in several subcortical structures whereas the number of these decreased in the anterior olfactory nucleus and some related cortical areas. In animals 25 days of age the intensity of immunostaining continued to increase, essentially producing the adult pattern in all except olfactory areas where there was a dramatic loss of ADA-immunoreactive cells. These results show that the restricted pattern of ADA-immunostaining observed in adult rat brain is generated over a protracted period of development, various stages of which are characterized predominantly by the expression of ADA in greater abundance, at least to the extent this can be gleaned immunohistochemically, in greater numbers of neurons and to a minor degree by a decreased capacity to express this enzyme.
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PMID:Development of adenosine deaminase-immunoreactive neurons in the rat brain. 381 18

The olfactory cortex slice preparation from guinea-pig has been used to test compounds which inhibit the cellular uptake of adenosine. The uptake inhibitors dipyridamole (0.1-10 mumol/l), dilazep (1-10 mumol/l) nitrobenzylthioguanosine (1-10 mumol/l), nitrobenzylthioinosine (0.1-5 mumol/l), and hexobendine (1-100 mumol/l) increased the potency of adenosine (0.1-30 mumol/l) by up to 5-fold but did not potentiate cyclohexyladenosine (0.01-10 mumol/l). The benzodiazepine, diazepam (1 mumol/l) slightly increased the potency of adenosine (by 1.7-fold) whereas flurazepam (3 mumol/l) had no effect, suggesting that inhibition of adenosine uptake is probably not the major therapeutic action of these compounds. The uptake inhibitors depressed the amplitude of the monosynaptic epsp when added alone, an effect reversed by adenosine deaminase (1 unit/ml) whereas the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (10 mumol/l) had no effect on adenosine action. These results show that in this preparation (a) adenosine action is attenuated by an uptake mechanism and (b) endogenous adenosine release normally has no apparent effects on synaptic transmission at low stimulus rates. Nitrobenzylthioinosine and nitrobenzylthioguanosine are probably the best uptake blockers.
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PMID:Effects of adenosine uptake blockers and adenosine on evoked potentials of guinea-pig olfactory cortex. 395 66

A highly heterogeneous distribution of [3H]nitrobenzylthioinosine [( 3H]NBI) binding sites was observed using both autoradiographic and membrane binding methodology. Of the 24 brain regions examined in the radio-ligand binding studies, the highest levels of [3H]NBI sites were found in the thalamus, followed by midbrain, superior colliculus, olfactory cortex and hypothalamus. The thalamus contained over 5 times more sites than cerebellum which exhibited the lowest [3H]NBI binding levels. The results obtained from autoradiographic analysis agreed well with quantitative measurements and revealed that subnuclei of thalamus and hypothalamus as well as specific layers of the superior colliculus contained particularly high concentrations of [3H]NBI sites. When the [3H]NBI autoradiograms were compared with the distribution of adenosine deaminase in brain it was found that brain regions richest in neural elements immunoreactive for adenosine deaminase contained the greatest numbers of [3H]NBI sites. In contrast, a poor correlation was found between the distribution of [3H]NBI binding and adenosine receptors labelled with [3H]cyclohexyladenosine. The co-localization of [3H]NBI binding and adenosine deaminase in brain indicates the existence of neural systems having a high capacity to take up and metabolize adenosine.
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PMID:Heterogeneous distribution of adenosine transport sites labelled by [3H]nitrobenzylthioinosine in rat brain: an autoradiographic and membrane binding study. 609 44

Aglycaemic/anoxic slices of rat olfactory cortex lose all electrical activity. On reoxygenation, 10 microM adenosine enhanced recovery from 23 +/- 7% to 53 +/- 12%; an increased tissue endurance of 5-7 min. 100 microM adenosine slightly depressed recovery to 11.5 +/- 2.1%. Dipyridamole increased whereas adenosine deaminase reduced recovery. These observations question the therapeutic effectiveness of high adenosine concentrations.
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PMID:Concentration dependence of adenosine and the protection of rat cortical neurones during anoxia. 780 33

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.
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PMID:RED2, a brain-specific member of the RNA-specific adenosine deaminase family. 894 18

The interferon-inducible RNA-specific adenosine deaminase (ADAR1) is an RNA-editing enzyme that catalyzes the deamination of adenosine in double-stranded RNA structures. Three alternative splice-site variants of ADAR1 (ADAR1-a, -b, and -c) occur that possess functionally distinct double-stranded RNA-binding motifs as measured with synthetic double-stranded RNA substrates. The pre-mRNA transcript encoding the B subunit of glutamate receptor (GluR-B) has two functionally important editing sites (Q/R and R/G sites) that undergo selective A-to-I conversions. We have examined the ability of the three ADAR1 splice-site variants to catalyze the editing of GluR-B pre-mRNA at the Q/R and R/G sites as well as an intron hotspot (+60) of unknown function. Measurement of GluR-B pre-mRNA editing in vitro revealed different site-specific deamination catalyzed by the three ADAR1 variants. The ADAR1-a, -b, and -c splice variants all efficiently edited the R/G site and the intron +60 hotspot but exhibited little editing activity at the Q/R site. ADAR1-b and -c showed higher editing activity than ADAR1-a for the R/G site, whereas the intron +60 site was edited with comparable efficiency by all three ADAR1 splice variants. Mutational analysis revealed that the functional importance of each of the three RNA-binding motifs of ADAR1 varied with the specific target editing site in GluR-B RNA. Quantitative reverse transcription-polymerase chain reaction analyses of GluR-B RNA from dissected regions of rat brain showed significant expression and editing at the R/G site in all brain regions examined except the choroid plexus. The relative levels of the alternatively spliced flip and flop isoforms of GluR-B RNA varied among the choroid plexus, cortex, hippocampus, olfactory bulb, and striatum, but in all regions of rat brain the editing of the flip isoform was greater than that of the flop isoform.
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PMID:Editing of glutamate receptor subunit B pre-mRNA by splice-site variants of interferon-inducible double-stranded RNA-specific adenosine deaminase ADAR1. 998 54


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