Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As part of an investigation of the organization of cell surface macromolecular assemblies, we have treated intact central nervous system cells with chemical probes which react convalently with proteins and aminophospholipids. Selective alterations of the enzymatic activities of ecto-ATPases, ecto-5'-nucleotidases and cholinesterases were obtained under appropriate reaction conditions. The cross-linking reagent, 1,5-difluoro-2,4-dinitrobenzene, was a potent inactivator of ecto-ATPase of C6 glioblastoma, IMR-32 neuroblastoma and of a primary rat astroblast cell line (RB). Ecto-5'-nucleotidase and acetylcholinesterase were less sensitive to difluorodinitrobenzene. 1-Fluoro-2,4-dinitrobenzene at concentrations which inactivated ecto-ATPase had little effect on ecto-5'-nucleotidase. Conversely, 2,4,6-trinitrobenzenesulfonic acid was a potent inactivator of ecto-5'-nucleotidase but had no effect on ecto-ATPase. The difluorodinitrobenzene inactivation of ecto-ATPase and of ecto-5'-nucleotidase as well as the fluorodinitrobenzene inactivation of ecto-ATPase could be prevented by the presence of the appropriate substrates in the reaction medium. In the presence of protecting nucleotide substrates, a decrease in reactivity with proteins and lipids was observed when the isotopic probe fluorodinitro[3H]-benzene was used.
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PMID:Selective chemical modification of plasma membrane ectoenzymes. 611 44

Carbofuran and malathion are broad spectrum pesticides widely used in agricultural practice throughout the world. Toxicity of these pesticides has been correlated with their inhibitory effects on acetylcholinesterase activity. Nucleotides are extracellular signaling molecules, which trigger multiple biological effects. Studies have demonstrated the co-transmission of acetylcholine and ATP at the nerve endings. The control of neurotransmitter ATP levels is promoted by enzymes named ectonucleotidases, which include nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5'-nucleotidase. Since acetylcholine and ATP are co-released at the synapse and the acetylcholinesterase inhibition is an important target for pesticide action, here we verified the effect of exposure in vitro and in vivo to carbofuran and malathion on ectonucleotidase activities from brain membranes of zebrafish. To verify if carbofuran and malathion have a direct inhibitory effect on NTPDase and 5'-nucleotidase activities in brain membranes of zebrafish, we have tested in vitro concentrations of pesticides varying from 0.25 to 5 mM. Carbofuran, in vitro, inhibited ATP and ADP hydrolysis in an uncompetitive manner, but no effect was observed on AMP hydrolysis. Malathion decreased ATP and ADP hydrolysis in competitive and an uncompetitive manner, respectively, but not altered AMP hydrolysis. After exposure to carbofuran (50 and 500 microg/L) during 7 days, ADP hydrolysis was significantly decreased in both concentrations tested (by 19 and 24.5%, respectively). Malathion, at 500 microg/L, was able to inhibit ADP and AMP hydrolysis (by 28 and 58.5%, respectively). This study has shown that ectonucleotidases from brain membranes of zebrafish can be a potential target for pesticide neurotoxicity.
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PMID:Carbofuran and malathion inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes. 1595 Oct 93

Zinc and cadmium are environmental contaminants that induce a wide range of effects on CNS. Here we tested the in vitro effect of these metals on acetylcholinesterase (AChE) and ectonucleotidase (NTPDase and ecto-5'-nucleotidase) activities in zebrafish brain. Both zinc and cadmium treatments did not alter significantly the zebrafish brain AChE activity. ATP hydrolysis presented a significant increase at 1 mM zinc (17%) and the AMPase activity had a dose-dependent increase at 0.5 and 1 mM zinc exposure (188% and 199%). After cadmium treatment, ATPase activity was significantly increased (53% and 48%) at 0.5 and 1 mM, respectively. Cadmium, in the range 0.25-1 mM, inhibited ADP hydrolysis in a dose-dependent manner (13.4-69%). Ecto-5'-nucleotidase activity was only inhibited (38%) in the presence of 1 mM cadmium. It is possible to suggest that changes on NTPDase and ecto-5'-nucleotidase activities can be an important mechanism involved in neurotoxic effects promoted by zinc and cadmium.
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PMID:In vitro effect of zinc and cadmium on acetylcholinesterase and ectonucleotidase activities in zebrafish (Danio rerio) brain. 1644 75

Besides the well-characterized inhibitory effect of adenosine in the gastrointestinal tract mediated by A1 receptors, we recently demonstrated that endogenously generated adenosine facilitates [3H]acetylcholine release from myenteric neurons through preferential activation of prejunctional A2A receptors. The co-existence of both receptor subtypes on cholinergic neurons prompted the question of how does adenosine discriminate between these receptors to regulate synaptic transmission in the longitudinal muscle-myenteric plexus (LM-MP) of the rat ileum. Electrical stimulation of the LM-MP increased the outflow of adenosine, inosine and hypoxanthine. Myenteric neurons seem to be the main source of endogenous adenosine, since blockade of action potentials with tetrodotoxin (1 microM) or omission of Ca2+ (plus EGTA, 1 mM) in the buffer essentially abolished nucleosides release, while adenosine outflow remained unchanged when smooth muscle contractions were prevented by nifedipine (1 microM). Inhibition of ecto-5'-nucleotidase by concanavalin A (0.1 mg ml-1) produced only a moderate decrease (approximately 25%) on adenosine accumulation in the LM-MP, indicating that the extracellular catabolism of released ATP might not be a major source of the nucleoside. Data using the acetylcholinesterase inhibitor, physiostigmine (10 microM), and several subtype-specific muscarinic receptor antagonists, 4-DAMP (100 nM), AF-DX 116 (10 microM) and muscarinic toxin-7 (1 nM), suggest that cholinergic motoneurons are endowed with muscarinic M3 autoreceptors facilitating the outflow of adenosine. Surprisingly, bath samples collected after stimulating the LM-MP exhibited a relatively high adenosine deaminase (ADA) activity (0.60+/-0.07 U ml-1), which increased in parallel with the accumulation of adenosine and its deamination products. Our findings are in keeping with the hypothesis that ADA secretion, along with a less-efficient dipyridamole-sensitive nucleoside transport system, may restrict endogenous adenosine actions to the synaptic region channelling to facilitatory A2A receptors activation. Such a local environment may also limit diffusion of exogenously added adenosine towards the active zones, as we showed that this constrain may be overcome by inhibiting ADA activity with erythro-9(2-hydroxy-3-nonyl) adenine (50 microM).
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PMID:Fine-tuning modulation of myenteric motoneurons by endogenous adenosine: on the role of secreted adenosine deaminase. 1656 76

Methanol is a neurotoxic compound that is responsible for serious damage on CNS. Besides being found as an environmental contaminant, this alcohol is also employed as a component of cryoprotector solutions for zebrafish embryos. Here we tested the acute effect of methanol on ecto-nucleotidase (NTPDase, ecto-5'-nucleotidase) and acetylcholinesterase (AChE) activities in zebrafish brain. After acute treatment, there were significant decreases on ATP (26% and 45%) and ADP hydrolysis (26% and 30%) at 0.5% and 1.0%, respectively. However, no significant alteration on ecto-5'-nucleotidase activity was verified in zebrafish brain. A significant inhibition on AChE activity (39%, 33% and 30%) was observed at the range of 0.25% to 1.0% methanol exposure. Four NTPDase sequences were identified from phylogenetic analyses, which one is similar to NTPDase1 and the others to NTPDase2. Methanol was able to inhibit NTPDase1, two isoforms of NTPDase2 and AChE transcripts. To evaluate if methanol affects directly these enzymes activities, we have performed in vitro assays. ATP hydrolysis presented a significant inhibition (19% and 34%) at 1.5% and 3.0%, respectively, and ADP hydrolysis decreased only at 3.0% (29.2%). Nevertheless, AMP hydrolysis and AChE were not altered after in vitro exposure. The inhibitory effect observed on these enzymes could contribute to the neurodegenerative events promoted by methanol in zebrafish brain.
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PMID:Methanol alters ecto-nucleotidases and acetylcholinesterase in zebrafish brain. 1680 13

Despite the great progress made in setting the basis for the molecular diversity of acetylcholinesterase (AChE), an explanation for the existence of two types of amphiphilic subunits, with and without glicosylphosphatidylinositol (GPI) (Types I and II), has not been provided yet. In searching whether, as for the deficiency of dystrophin, that of merosin (laminin-alpha2 chain) alters the number of caveolae in muscle, a high increase in caveolin-3 (Cav3) was observed in the Triton X-100-resistant membranes (TRM) isolated from muscle of merosin-deficient dystrophic mice (Lama2dy). The rise in Cav3 was accompanied by that of non-caveolar lipid rafts, as showed by the greater ecto-5'-nucleotidase (eNT) activity, a marker of non-caveolar rafts, in TRM of dystrophic muscle. The observation of AChE activity in TRM, the increased levels of rafts and raft-bound AChE activity in merosin-deficient muscle and the presence of phospholipase C-sensitive AChE dimers in TRM supported targeting of glypiated AChE to rafts. This issue and the involvement of TRM in conveying nicotinic receptors to the neuromuscular junction and particular muscarinic receptors to cardiac sarcolemma strongly support a role for lipid rafts in targeting ACh receptors and glypiated AChE. Their nearby location in the surface membrane may provide cells with a fine tuning for regulating cholinergic responses.
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PMID:Targeting of acetylcholinesterase to lipid rafts of muscle. 1851 10

Wild type and dystrophic (merosin-deficient) Lama2dy mice muscles were compared for their density of lipid rafts. The 5-fold higher level of caveolin-3 and the 2-3 times higher level of ecto-5'-nucleotidase activity in raft preparations (Triton X-100-resistant membranes) of dystrophic muscle supported expansion of caveolar and non-caveolar lipid rafts. The presence in rafts of glycosylphosphatidylinositol (GPI)-linked acetylcholinesterase (AChE) dimers, which did not arise from erythrocyte or nerve, not only revealed for the first time the capacity of the myofibre for translating the AChE-H mRNA but also an unrecognized pathway for targeting AChE-H to specialized membrane domains of the sarcolemma. Rafts of dystrophic muscle contained a 5-fold higher AChE activity/mg protein. RT-PCR for 3'-alternative mRNAs of AChE revealed AChE-T mRNA prevailing over AChE-R and AChE-H mRNAs in wild type mouse muscle. It also displayed principal 5'-alternative AChE mRNAs with exons E1c and E1e (the latter coding for N-terminally extended subunits) and fewer with E1d, E1a and E1b. The levels of AChE and butyrylcholinesterase mRNAs were unaffected by dystrophy. Finally, the decreased level of proline-rich membrane anchor (PRiMA) mRNA in Lama2dy muscle provided for a rational explanation to the loss of PRiMA-bearing AChE tetramers in dystrophic muscle.
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PMID:The levels of both lipid rafts and raft-located acetylcholinesterase dimers increase in muscle of mice with muscular dystrophy by merosin deficiency. 2067 Sep 15

The zebrafish (Danio rerio) is an emergent model organism for assessing fear and anxiety-like phenotypes. The short fin wild type (WT), and leopard (leo) are two zebrafish populations that present several behavioral differences, in which leo displays pronounced defensive responses. Mounting evidence suggests a modulatory role for cholinergic and purinergic signaling in fear and anxiety, but the involvement of these neurotransmitter systems in the behavioral profile of zebrafish is obscure. Here we tested whether the acute exposure to conspecific alarm substance (AS), an experimental protocol that induces fear, alters shoaling behavior, diving response, acetylcholinesterase (AChE) activity, and nucleotide hydrolysis in brain tissue of WT and leo. When four fish were concomitantly exposed to AS extracted from a donor fish of similar phenotype, both populations presented a significant increase of erratic movements without changes in freezing bouts. An increased shoal cohesion and a decreased vertical distribution were observed only in WT exposed to AS. The respective population also revealed a significant increase in AChE and ecto-5'-nucleotidase activities after the exposure period. The comparison of basal endpoints between populations showed that leo displays a higher social cohesion, few vertical transitions and enhanced AChE and ecto-5'-nucleotidase activities. In conclusion, we suggest that the effects of AS on defensive behaviors depend on the population, indicating the existence of distinct neurochemical mechanisms involved. Furthermore, this report shows the first evidence of a potential role of cholinergic and purinergic systems in fear- and anxiety-like responses of zebrafish populations.
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PMID:Conspecific alarm substance differently alters group behavior of zebrafish populations: Putative involvement of cholinergic and purinergic signaling in anxiety- and fear-like responses. 2800 36