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)

Projections from the tuberomammillary nucleus (TM) to widespread regions within the hypothalamus were evaluated using a combined immunohistochemical-retrograde fluorescent tracing procedure. Injections of Fluoro-gold into the anterior hypothalamus labelled TM neurons identified by their immunoreactivity for the enzyme adenosine deaminase (ADA). Small injections of Fluoro-gold into the posterior hypothalamus also led to the labelling of TM neurons. The numbers of ADA-immunoreactive axonal varicosities were 5 times greater in the hypothalamus than in most other brain regions. The results indicate that the hypothalamus represents a major projection area of the TM.
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PMID:The hypothalamus receives major projections from the tuberomammillary nucleus in rat. 310 29

The somas of primary afferent neurons in the mesencephalic nucleus of the trigeminal nerve in rat have a dense investment of axons immunoreactive for the enzyme adenosine deaminase. We previously suggested that these axons may originate from adenosine deaminase-immunoreactive neurons located in the tuberomammillary nucleus of the hypothalamus [Nagy et al. (1986) Neuroscience 17, 141-156]. Anterograde tracing and immunohistochemical techniques were used to investigate this possibility further. In addition, the appearance of adenosine-immunoreactive axons and the nature of their interactions with mesencephalic neurons was examined ultrastructurally. After injections of either Phaseolus vulgaris-leucoagglutinin or wheat germ agglutinin-horseradish peroxidase into the region of the tuberomammillary nucleus, punctate deposits of anterogradely transported tracer, detected by immunoperoxidase methods, were seen surrounding mesencephalic neurons. In sections immunostained for tracer and adenosine deaminase by double immunofluorescence, some fibres in the periaqueductal gray matter and around Mes V somas were found to be labelled for both the lectin and the enzyme. Ultrastructurally, only a single morphological class of adenosine deaminase-immunoreactive axons adjacent to, or indenting the cytoplasmic membranes of, large somas in the mesencephalic nucleus could be recognized; they were varicose and contained relatively large immunoreactive vesicles ranging in diameter from 45 to 70 nm. Occasionally, thin processes of these axons could be traced back to small adenosine deaminase-positive neuronal cell bodies located not within the tuberomammillary nucleus, but rather, within the periaqueductal gray matter. In serial ultrathin sections, membrane specializations resembling synaptic junctions were sometimes seen at points where mesencephalic somas were in contact with adenosine deaminase-immunoreactive terminals. Somas within the mesencephalic nucleus also formed such junctions with non-immunoreactive boutons which were morphologically different from, and often seen in close proximity to, those containing adenosine deaminase. These results indicate that in addition to possible afferents from the tuberomammillary nucleus, primary sensory somas within the mesencephalic nucleus are also associated with axonal processes originating from adenosine deaminase-positive neurons located within the periaqueductal gray matter. The infrequent synaptic contacts between these somas and adenosine deaminase-positive axons, despite their close anatomical arrangement, is suggestive of a diffuse endocrine or neurocrine type of axonal relationship with mesencephalic somas or with the n
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PMID:Further observations on the relationship between adenosine deaminase-containing axons and trigeminal mesencephalic neurons: an electron microscopic, immunohistochemical and anterograde tracing study. 317 93

In addition to their well known roles within cells, purine nucleotides such as adenosine 5' triphosphate (ATP) and guanosine 5' triphosphate (GTP), nucleosides such as adenosine and guanosine and bases, such as adenine and guanine and their metabolic products xanthine and hypoxanthine are released into the extracellular space where they act as intercellular signaling molecules. In the nervous system they mediate both immediate effects, such as neurotransmission, and trophic effects which induce changes in cell metabolism, structure and function and therefore have a longer time course. Some trophic effects of purines are mediated via purinergic cell surface receptors, whereas others require uptake of purines by the target cells. Purine nucleosides and nucleotides, especially guanosine, ATP and GTP stimulate incorporation of [3H]thymidine into DNA of astrocytes and microglia and concomitant mitosis in vitro. High concentrations of adenosine also induce apoptosis, through both activation of cell-surface A3 receptors and through a mechanism requiring uptake into the cells. Extracellular purines also stimulate the synthesis and release of protein trophic factors by astrocytes, including bFGF (basic fibroblast growth factor), nerve growth factor (NGF), neurotrophin-3, ciliary neurotrophic factor and S-100beta protein. In vivo infusion into brain of adenosine analogs stimulates reactive gliosis. Purine nucleosides and nucleotides also stimulate the differentiation and process outgrowth from various neurons including primary cultures of hippocampal neurons and pheochromocytoma cells. A tonic release of ATP from neurons, its hydrolysis by ecto-nucleotidases and subsequent re-uptake by axons appears crucial for normal axonal growth. Guanosine and GTP, through apparently different mechanisms, are also potent stimulators of axonal growth in vitro. In vivo the extracellular concentration of purines depends on a balance between the release of purines from cells and their re-uptake and extracellular metabolism. Purine nucleosides and nucleotides are released from neurons by exocytosis and from both neurons and glia by non-exocytotic mechanisms. Nucleosides are principally released through the equilibratory nucleoside transmembrane transporters whereas nucleotides may be transported through the ATP binding cassette family of proteins, including the multidrug resistance protein. The extracellular purine nucleotides are rapidly metabolized by ectonucleotidases. Adenosine is deaminated by adenosine deaminase (ADA) and guanosine is converted to guanine and deaminated by guanase. Nucleosides are also removed from the extracellular space into neurons and glia by transporter systems. Large quantities of purines, particularly guanosine and, to a lesser extent adenosine, are released extracellularly following ischemia or trauma. Thus purines are likely to exert trophic effects in vivo following trauma. The extracellular purine nucleotide GTP enhances the tonic release of adenine nucleotides, whereas the nucleoside guanosine stimulates tonic release of adenosine and its metabolic products. The trophic effects of guanosine and GTP may depend on this process. Guanosine is likely to be an important trophic effector in vivo because high concentrations remain extracellularly for up to a week after focal brain injury. Purine derivatives are now in clinical trials in humans as memory-enhancing agents in Alzheimer's disease. Two of these, propentofylline and AIT-082, are trophic effectors in animals, increasing production of neurotrophic factors in brain and spinal cord. Likely more clinical uses for purine derivatives will be found; purines interact at the level of signal-transduction pathways with other transmitters, for example, glutamate. They can beneficially modify the actions of these other transmitters.
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PMID:Trophic effects of purines in neurons and glial cells. 1084 57

A splice variant of choline acetyltransferase mRNA has recently been identified in the pterygopalatine ganglion of rat. An antibody against this variant protein (designated pChAT) was demonstrated to immunolabel peripheral cholinergic neurons. In the present study, we investigated the expression of pChAT in rat brain. Amongst the brain regions examined, magnocellular neurons in the tuberomammillary nucleus of the posterior hypothalamus were immunohistochemically labelled with anti-pChAT antibody, whilst no immunolabelling was detected in cholinergic neurons in the basal forebrain or striatum. RT-PCR analysis confirmed the expression of pChAT mRNA in the posterior hypothalamus. The distribution of pChAT-positive neurons in the tuberomammillary nucleus was compared with that of neurons positive for adenosine deaminase, which is contained in all neurons of this nucleus. After colchicine treatment to inhibit axonal transport of enzyme, virtually all pChAT-positive cells contained adenosine deaminase. Conversely, about 85% of adenosine deaminase-positive cells contained pChAT in the ventral area, whilst 19% of adenosine deaminase-positive cells were pChAT-positive in the dorsal area. Long axonal projections of pChAT-positive cells in the tuberomammillary nucleus were shown by retrograde labelling of these cells after injection of cholera-toxin B subunit into the cerebral cortex. This study demonstrates that a splice variant of choline acetyltransferase is expressed in the tuberomammillary nucleus of rat. The results raise the possibility that some of the known diverse projection areas of this nucleus may have a cholinergic component.
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PMID:Expression of a splice variant of choline acetyltransferase in magnocellular neurons of the tuberomammillary nucleus of rat. 1267 54

In the first series of experiments, a retrograde tracer, WGA-apo-HRP-gold (WG), was injected into the dorsal raphe (DR) or the locus coeruleus (LC) and adenosine deaminase immunostaining was subsequently performed for the tuberomammillary nucleus (TMN) in order to investigate projections from the TMN to the two brainstem monoaminergic nuclei. Following rostral DR injections, the majority of retrogradely labeled cells were located in the dorsomedial and ventrolateral subdivisions of the TMN. At middle DR levels, midline injections resulted in labeling mainly in the ventrolateral subdivision, whereas lateral wing injections produced labeling mostly in ventral and caudal TMN subdivisions. When injections were made in the caudal DR, only a few cells were observed along the rostro-caudal extent of the TMN. On the other hand, following rostral LC injections, labeled neurons were observed mainly in ventrolateral and ventral subdivisions of TMN. For principal LC injections, labeled cells were observed mostly in ventrolateral, ventral, and caudal TMN subdivisions, whereas for injections at caudal pole of LC, only a few cells were located along the rostro-caudal extent of the TMN. In the second series of experiments, an iontophoretic injection of fluorogold (FG) into the DR was paired with a pressure injection of WG into the LC to investigate the collateral distribution of TMN axonal fibers to DR and LC. Double-labeled cells were observed in ventrolateral, ventral, and caudal TMN subdivisions. The present study indicated that there exists a robust projection from the TMN to the DR or the LC and that some TMN neurons have axon collaterals projecting to both DR and LC. The TMN neurons with such axon collaterals might provide simultaneous, possibly more efficient, way of controlling the brainstem monoaminergic nuclei, thus influencing various sleep and arousal states of the animal.
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PMID:Retrograde study of projections from the tuberomammillary nucleus to the dorsal raphe and the locus coeruleus in the rat. 1586 19

Fragile X syndrome (FXS) is the most frequent inherited form of mental retardation. The cause for this X-linked disorder is the silencing of the fragile X mental retardation 1 (fmr1) gene and the absence of the fragile X mental retardation protein (Fmrp). The RNA-binding protein Fmrp represses protein translation, particularly in synapses. In Drosophila, Fmrp interacts with the adenosine deaminase acting on RNA (Adar) enzymes. Adar enzymes convert adenosine to inosine (A-to-I) and modify the sequence of RNA transcripts. Utilizing the fmr1 zebrafish mutant (fmr1-/-), we studied Fmrp-dependent neuronal circuit formation, behavior, and Adar-mediated RNA editing. By combining behavior analyses and live imaging of single axons and synapses, we showed hyperlocomotor activity, as well as increased axonal branching and synaptic density, in fmr1-/- larvae. We identified thousands of clustered RNA editing sites in the zebrafish transcriptome and showed that Fmrp biochemically interacts with the Adar2a protein. The expression levels of the adar genes and Adar2 protein increased in fmr1-/- zebrafish. Microfluidic-based multiplex PCR coupled with deep sequencing showed a mild increase in A-to-I RNA editing levels in evolutionarily conserved neuronal and synaptic Adar-targets in fmr1-/- larvae. These findings suggest that loss of Fmrp results in increased Adar-mediated RNA editing activity on target-specific RNAs, which, in turn, might alter neuronal circuit formation and behavior in FXS.
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PMID:Fmrp Interacts with Adar and Regulates RNA Editing, Synaptic Density and Locomotor Activity in Zebrafish. 2663 67