Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of adenosine A1 receptors in the human brain was studied by autoradiography in post mortem brain tissues from 26 subjects without reported neurological disease. N6-[3H]Cyclohexyl-adenosine was used as the ligand. For comparison, adjacent sections of some regions were examined histochemically for 5'-nucleotidase activity. The receptor sites were heterogeneously distributed throughout the CNS. The highest receptor densities were found in the stratum oriens, pyramidale and radiatum of the hippocampus. High densities were also found in the cerebral cortex and the striatum. In the thalamus there was a heterogeneous distribution of binding sites with a high density in structures such as the medial and anterior nucleus. Intermediate receptor densities were found in the accumbens, the olfactory tubercle and most parts of the amygdala among others. The hypothalamus had low receptor densities. In the brainstem and the spinal cord very low receptor concentrations were found. However, in some structures such as the substantia nigra, the colliculus superior and the substantia gelatinosa of the spinal cord a low level of binding could be measured. The cerebellar cortex showed low densities of receptors. Structures showing high levels of 5'-nucleotidase activity were the hippocampus, the striatum and parts of the cerebral cortex among other regions. In general there was a poor correlation between the localization of A1 receptors and the 5'-nucleotidase activity. Some regions, however, showed a similar distribution of these two markers. In general, the distribution of adenosine A1 receptors found in the human brain is comparable to that found in previous autoradiographic studies in the rat brain. However, some regional differences were observed in, for example, the cerebral cortex, the striatum and the cerebellar cortex. These differences may prove to be functionally relevant.
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PMID:Adenosine A1 receptors in the human brain: a quantitative autoradiographic study. 282 71

In hyperhistidinaemic squirrels, changed activities of acid phosphatase and 5'-nucleotidase have been observed in the olfactory lobes and cerebral hemispheres. The possible significance of lowered activity of these lysosomal enzymes in the hyperhistidinaemic brain have been discussed.
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PMID:Acid phosphatase and 5'-nucleotidase activities in the brain of squirrels (Funambulus palmarum) with experimentally induced hyperhistidinaemia. 626 68

The activities of 5'-nucleotidase, 2'-nucleotidase, alkaline phosphatase, and acid phosphatase were measured in rat and autopsied human brains. The four phosphatases in the rat brain showed little change in activity after death. The activities of adenosine-producing enzymes were compared in various parts of rat and human brains. When phosphatase activity was measured at pH 7.5, 5'-nucleotidase showed the highest activity in the most parts of the brain. The activity of 2'-nucleotidase and that of nonspecific phosphatase were almost the same at pH 7.5. However, higher phosphatase activity was observed in all parts of the brain when nonspecific phosphatase activity was measured at pH 10.0 or 5.5. High specific activity of 5'-nucleotidase in the brain was detected in the membranous components, especially in the synaptic membranes. The activity of 2'-nucleotidase was distributed in the soluble and synaptosomal fractions. The highest activity of both alkaline and acid phosphatases was recovered in the crude mitochondrial fraction, with the highest specific activity in the microsomal fraction. Phosphatase activity was distributed widely in the rat brain. The activity of 5'-nucleotidase was high in the medulla oblongata, thalamus, and hippocampus, but low in the peripheral nerve, spinal cord, and occipital lobe. The activity of 2'-nucleotidase was high in the vermis and frontal lobe. The highest acid and alkaline phosphatase activities were detected in the frontal lobe and in the olfactory bulb, respectively. The distribution of the four phosphatases in the autopsied human brain was similar to that in the rat brain. The highest 5'-nucleotidase activity was observed in the temporal lobe and thalamus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional and subcellular distribution in mammalian brain of the enzymes producing adenosine. 632 54

The adenosine-producing ecto-enzyme 5'-nucleotidase has recently been assigned to malleable axon terminals in both the developing and regenerating adult nervous system, but is otherwise only glia-bound. Using a cytochemical lead method, we now show that 5'-nucleotidase activity is localized predominantly at glomerular and mitral synapses within the main olfactory bulb of normal, adult rats. As these terminals are prone to synaptic turnover even at maturity, the present findings favour the view that this enzyme constitutes a marker molecule for plastic synapses. It is suggested that functions of 5'-nucleotidase in purinergic neuromodulation and cell adhesion are unique to the olfactory bulb, and implied in synaptic arrangements and information processing.
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PMID:Evidence that 5'-nucleotidase is associated with malleable synapses--an enzyme cytochemical investigation of the olfactory bulb of adult rats. 775 5

The distribution of the adenosine-producing ecto-enzyme 5'-nucleotidase was investigated histochemically in the developing rat olfactory bulb. Rat pups underwent either unilateral surgical occlusion of the right external naris or sham surgery on postnatal day 1. At 10, 20, or 30 days postpartum, horizontal sections of the olfactory bulb were reacted histochemically to reveal the locus and intensity of 5'-nucleotidase activity. Relative staining levels were determined by optical densitometry in standardized bulb regions. A marked, age-related increase in staining density was observed. Reaction product was found primarily in neuropil areas. The P10 and P20 control animals did not exhibit right/left differences in bulb staining; however, some laterality was observed in P30 animals. Inter-glomerular and regional variations were observed throughout the developmental period, including (1) differences between neighboring glomeruli; (2) a gradient in the dorsal-ventral axis of the bulb; and (3) a higher staining density in the medial-caudal portion of the bulb. In subjects with occluded nares, asymmetries in right/left bulb 5'-nucleotidase staining patterns were detected throughout development. Bulbs ipsilateral to the blocked nares exhibited increased staining density, suggesting that the procedure enhanced enzymatic activity. Understanding these variations in 5'-nucleotidase staining may be important for a complete understanding of the mechanisms of olfactory bulb maturation and may give insight into the possible role of this enzyme in synaptic malleability during nervous system development and regeneration.
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PMID:Development of 5'-nucleotidase staining in the olfactory bulbs of normal and naris-occluded rats. 901 Jul 33

The demonstration of 5'-nucleotidase in neural tissue is achieved at both the light and electron microscopic levels by means of an enzyme cytochemical lead method, which is specific, sensitive and fast. By its activity this adenosine-producing ecto-enzyme (EC 3.1.3.5) outlines cellular surface membranes at the ultrastructural level. It is classically known as a marker of myelin and of astrocytes as well as (activated) microglial cells in the mature nervous system. In recent years, we discovered that 5'-nucleotidase is transiently active within synaptic clefts under conditions of development and regeneration. The enzyme is also seen at terminals in the mature retina and olfactory bulb, where spontaneous synaptic turnover occurs at adulthood. Thus, 5'-nucleotidase cytochemistry is useful in revealing sites of glial reactions and synaptic plasticity in CNS development and repair. It is assumed that the molecule affects terminal formation and cell motility due to dual functions in adenosine production and cell adhesion. Finally, at the light microscopic level, 5'-nucleotidase activity displays a dense neuropil staining which identifies topographic sub-units of certain parts of the nervous system, such as the striosomes of the basal ganglia, ocular dominance columns of the visual cortex and parasagittal bands of the cerebellum.
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PMID:5'-nucleotidase enzyme cytochemistry as a tool for revealing activated glial cells and malleable synapses in CNS development and regeneration. 938 45

A unique feature of the olfactory epithelium is its ability to give rise to new sensory neurons throughout life and also following injury. Cells at the basal side of the epithelium serve as neurogenic progenitor cells. The enzyme ecto-5'-nucleotidase is expressed at the surface of developing nerve cells and is regarded as a marker of neural development. To study the expression pattern of the enzyme, we analyzed its distribution in the adult and developing rat olfactory organ. Labeling is restricted to specific cell types and varies between the epithelia investigated. At the basal side of the olfactory epithelium, activity of 5'-nucleotidase is associated specifically with the dark/horizontal basal cells. Neither the light/globose basal cells, which are the immediate precursors of the sensory receptor cells, nor subsets of potentially immature olfactory receptor cells are labeled. On the other hand, microvillar cells dispersed at the lumenal side of the epithelium contain 5'-nucleotidase activity. The enzyme is also present at the inner lining of the ducts of Bowman's glands as they traverse the epithelium. Within the respiratory epithelium, activity of 5'-nucleotidase is associated with basal cells as well as with the epithelial surface. During development, 5'-nucleotidase is initially limited to the respiratory epithelium, including its basal cells. Dark/horizontal basal cells of the olfactory epithelium, which are positive for 5'-nucleotidase, first appear at the border of the respiratory epithelium, suggesting that they might originate from immigrating basal cells of the respiratory epithelium. Within the vomeronasal organ, labeling is largely restricted to the receptor-free epithelium. Although the functional role of 5'-nucleotidase in the olfactory system needs to be further defined, the distribution of the enzyme can be used successfully as a marker for defined cell types.
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PMID:Association of ecto-5'-nucleotidase with specific cell types in the adult and developing rat olfactory organ. 955 Jan 56

CD73 (ecto-5'-nucleotidase) is a cell surface enzyme that regulates purinergic signalling by desphosphorylating extracellular AMP to adenosine. 5'-nucleotidases are known to be expressed in brain, but the expression of CD73 and its putative physiological functions at this location remain elusive. Here we found, using immunohistochemistry of wild-type and CD73 deficient mice, that CD73 is prominently expressed in the basal ganglia core comprised of striatum (caudate nucleus and putamen) and globus pallidus. Furthermore, meninges and the olfactory tubercle were found to specifically express CD73. Analysis of wild type (wt) and CD73 deficient mice revealed that CD73 confers the majority of 5'-nucleotidase activity in several areas of the brain. In a battery of behavioural tests and in IntelliCage studies, the CD73 deficient mice demonstrated significantly enhanced exploratory locomotor activity, which probably reflects the prominent expression of CD73 in striatum and globus pallidus that are known to control locomotion. Furthermore, the CD73 deficient mice displayed altered social behaviour. Overall, our data provide a novel mechanistic insight into adenosinergic signalling in brain, which is implicated in the regulation of normal and pathological behaviour.
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PMID:CD73 is a major regulator of adenosinergic signalling in mouse brain. 2377

Glioblastoma is the most devastating primary brain tumor. Effective therapies are not available, mainly due to high tumor heterogeneity, chemoresistance, and the difficulties imposed by blood-brain barrier. CD73, an enzyme responsible for adenosine (ADO) production, is overexpressed in cancer cells and emerges as a target for glioblastoma treatment. Indeed, ADO causes a variety of tumor-promoting actions, particularly by inducing tumor immune escape, whereas CD73 inhibition impairs tumor progression. Here, a cationic nanoemulsion to deliver CD73siRNA (NE-siRNA CD73R) via nasal route aiming glioblastoma treatment was developed. NE-siRNA CD73R was uptaken by glioma cells in culture, resulting in a parallel 60-80% decrease in AMPase activity and 30-50% in cell viability. Upon nasal delivery, NE-siRNA CD73R was detected in rat brain and serum. Notably, treatment with CD73siRNA complexes of glioma-bearing Wistar rats reduced tumor growth by 60%. Additionally, NE-siRNA CD73R treatment decreased 95% ADO levels in liquor and tumor CD73 expression, confirming in vivo CD73 silencing. Finally, no toxicity was observed in either primary astrocytes or rats with this cationic nanoemulsion. These results suggest that nasal administration of cationic NE as CD73 siRNA delivery system represents a novel potential treatment for glioblastoma. Graphical Abstract Glioblastoma is the most common and devastating form of primary brain tumor. CD73, a protein involved in cell-cell adhesion and migration processes and also responsible for extracellular adenosine (ADO) production, is overexpressed by glioma cells and emerges as an important target for glioma treatment. Indeed, ADO participates in tumor immune escape, cell proliferation, and angiogenesis, and CD73 inhibition impairs those processes. Here, a cationic nanoemulsion to deliver CD73 siRNA (NE-siRNA CD73R) via nasal route aiming glioblastoma treatment was developed. NE-siRNA CD73R knockdown in vitro and in vivo CD73. Upon nasal delivery of NE-siRNA CD73R, the treatment markedly reduced tumor volume by 60% in a rat preclinical glioblastoma model. The treatment was well tolerated, and did not induce kidney, liver, lung, olfactory, bone marrow, or behavior alterations. These results indicate that the nasal administration of NE as a CD73 siRNA delivery system offered an efficient means of gene knockdown and may represent a potential alternative for glioblastoma treatment.
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PMID:Nasal Administration of Cationic Nanoemulsions as CD73-siRNA Delivery System for Glioblastoma Treatment: a New Therapeutical Approach. 3140 44