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:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purification of axonal membranes of crustaceans was followed by measuring enrichment in [3H]tetrodotoxin binding capacity and in Na+, K+-ATPase activity. A characteristic of these membranes is their high content of lipids and their low content of protein as compared to other types of plasmatic membranes. The axonal membrane contains myosin-like, actin-like, tropomyosin-like, and tubulin-like proteins. It also contains Na+, K+-ATPase and acetylcholinesterase. The molecular weights of these two enzymes after solubilization are 280,000 and 270,000, respectively. The molecular weights of the catalytic subunits are 96,000 for ATPase and 71,000 for acetylcholinesterase. We confirmed the presence of a nicotine binding component in the axonal membrane of the lobster but we have been unable to find [3H]nicotine binding to crab axonal membranes. The binding to axonal membranes og of the sodium channel, has been studied in detail. The dissociation constant for the binding of [3H]tetrodotoxin to the axonal membrane receptor is 2.9 nM at pH 7.4. The concentration of the tetrodotoxin receptor in crustacean membranes is about 10 pmol/mg of membrane protein, 7 times less than the acetylcholinesterase, 30 times less than the Na+, K+-ATPase, and 30 times less than the nicotine binding component in the lobster membrane. A reasonable estimate indicates that approximately only one peptide chain in 1000 constitutes the tetrodotoxin binding part of the sodium channel in the axonal membrane. Veratridine, which acts selectively on the resting sodium permeability, binds to the phospholipid part of the axonal membrane. [3H]Veratridine binding to membranes parallels the electrophysiological effect. Veratridine and tetrodotoxin have different receptor sites. Although tetrodotoxin can repolarize the excitable membrane of a giant axon depolarized by veratridine, veratridine does not affect the binding of [3H]tetrodotoxin to purified axonal membranes. Similarly, tetrodotoxin does not affect the binding of [3H]veratridine to axonal membranes. Scorpion neurotoxin I, a presynaptic toxin which affects both the Na+ and the K+ channels, does not interfere with the binding of [3H]tetrodotoxin or [3H]veratridine to axonal membranes. Tetrodotoxin, veratridine, and scorpion neurotoxin I, which have in common the perturbation of the normal functioning of the sodium channel, act upon three different types of receptor sites.
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PMID:Constitution and properties of axonal membranes of crustacean nerves. 0 58

The biochemical properties of the electrically excitable sodium channels in the electroplaque of Electrophorus electricus were investigated using tritiated tetrodotoxin (TTX) as a specific membrane probe. Membrane fragments from the electroplaque were isolated essentially by differential centrifugation and characterized with respect to the plasma membrane markers acetylcholine receptors, acetylcholinesterase, (Na+ + K+)ATPase, and [3H]TTX binding. Equilibrium binding studies showed that [3H]TTX bound to a single population of noninteracting receptor sites with an apparent dissociation constant of 6 +/- 1 X 10(-9) M. The toxin-membrane complex dissociated with a first-order rate constant of 0.012 sec-1. Studies on the pH dependence of complex formation demonstrated the requirement for an ionizable, functional group with a pK of 5.3 and this group has been shown to be a carboxyl. Treatment of the membranes with trimethyloxonium tetrafluoroborate, a carboxyl group modifying reagent, resulted in an irreversible loss in the binding of [3H]TTX, which could be prevented by low concentrations of TTX or saxitoxin. This decrease was due to a reduction in the total number of binding sites and not to a decrease in toxin binding affinities. The relative binding affinities of various monovalent alkali metal and polyatomic cations for the TTX-receptor site showed that this site displayed cation discrimination properties which were similar to those reported previously for the electrically excitable sodium channel in intact nerve fibers. A possible role for this site in the ion selectivity of the sodium channel is proposed.
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PMID:Properties of the tetrodotoxin binding component in plasma membranes isolated from Electrophorus electricus. 0 13

Inhibition of cell division and outgrowth of neurites with average rate of 31.5 +/- 4.4 micrometers per hour were observed in neuroblastoma cultures of the Neuro 2a clonal line 24 hours after the increase in the culture medium pH from 7.4 to 8.2. The total neurite length per one cell was about 298 +/- 36 micron in average by the 9-10th days of treatment. Simultaneously, a gradual enhancement of acetylcholinesterase cytochemical appearance took place attaining its maximum level by the same time. The peak sodium conductance, taken as a measure of sodium tetrodotoxin-sensitive potential-dependent channel density, was the same both in nondifferentiated cells grown in suspension or monolayer cultures, and in morphologically differentiated ones. The data lead to a conclusion that biochemical (acetylcholinesterase probe) and electrophysiological (sodium channel density) signs can express independently of morphological differentiation.
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PMID:[Acetylcholinesterase expression and changes in the electrical excitability of neuroblastoma cells during their morphological differentiation induced by an increase in the pH of the medium]. 245 61

When grown in primary cell culture in the absence of neurons, muscle cells from a variety of species synthesize several forms of acetylcholinesterase (AChE), including the collagen-tailed A12 form. A12 AChE has been the subject of much study because it is thought to be a major functional enzyme form normally found in the basal lamina at the neuromuscular junction. In this paper, we show that muscle fibers derived from mouse embryos and neonates are also able to synthesize substantial percentages of their AChE as the A12 form when grown in vitro. This synthesis is modulated by a process associated with spontaneous muscle contractile activity since both total enzyme levels and the proportion of A12 AChE expressed on the cell surface are decreased when the cells are grown in the sodium channel blocker tetrodotoxin, which blocks muscle contraction. On the other hand, when the cells are treated with veratridine, which opens sodium channels, thereby mimicking one aspect of muscle contraction, their AChE levels are comparable to those of untreated cells. Although smaller in magnitude, these changes are similar to those seen in rat muscle cultures. A novel feature of mouse muscle cultures, not seen in those from rat and chick, is the presence of a secreted enzyme form that sediments in the same position as the cellular A12 form (when separated on sucrose density gradients containing high salt) and is also collagenase sensitive.
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PMID:Cellular and secreted forms of acetylcholinesterase in mouse muscle cultures. 405 99

1. The synthetic cationic polypeptide, poly-L-arginine (0.03-1 mg ml-1) induced concentration-dependent contraction of guinea-pig and rat isolated trachea. In guinea-pig isolated trachea, this response was attenuated in the presence of the muscarinic cholinoceptor antagonist, atropine (0.1 microM) and augmented by the acetylcholinesterase inhibitor, ecothiophate (0.1 microM). The neuronal sodium channel blocker, tetrodotoxin (3 microM) failed to alter the contractile response to poly-L-arginine and acetylcholine. 2. The contractile response to poly-L-arginine in rat isolated trachea was inhibited in the presence of atropine (0.1 microM) and the 5-hydroxytryptamine (5-HT) receptor antagonist, methysergide (1 microM). Treatment of rat tracheal preparations with capsaicin (100 microM) or tetrodotoxin (3 microM) failed to alter the contractile response to poly-L-arginine. In contrast, ecothiophate (0.1 microM) augmented the contractile response to poly-L-arginine in rat isolated trachea. 3. Electrical field stimulation (5 Hz, 2 min) of epithelium-denuded guinea-pig tracheal preparations preloaded with [3H]-choline resulted in a contractile response and the simultaneous efflux of radioactivity into the superfusate. Both these responses were abolished in the presence of tetrodotoxin (1.5 microM). Poly-L-arginine (1 mg ml-1) also increased the efflux of total radioactivity from epithelium-denuded guinea-pig isolated tracheal preparations preloaded with [3H]-choline, but this response was tetrodotoxin-insensitive. The negatively charged polyanion, heparin (1 mg ml-1) failed to increase significantly the efflux of radioactivity from epithelium-denuded preparations. 4.In conclusion, the synthetic cationic polypeptide, poly-L-arginine, caused contraction of guinea-pig isolated tracheal preparations via the release of acetylcholine from parasympathetic nerves. Similarly,poly-L-arginine-induced contraction of rat isolated trachea is secondary to the release of acetylcholine from parasympathetic nerves and/or the release of mast cell-derived 5-HT.
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PMID:Poly-L-arginine-mediated release of acetylcholine from parasympathetic nerves in rat and guinea-pig airways. 792 18

The widespread use of insecticides has amounted to a large scale 'experiment' in natural selection of insects by chemicals of toxicological importance to humans. Specific examples in which the molecular basis of insecticide resistance has been studied in detail are presented here. The biochemical/physiological mechanisms of resistance can be categorized as target site insensitivity, increased metabolic detoxification and sequestration or lowered availability of the toxicant. These are achieved at the molecular level by: point mutations in the ion channel portion of a GABA receptor subunit (cyclodiene insecticides); point mutations in the vicinity of the acetylcholinesterase (AChE) active site (organophosphorus and carbamate insecticide resistance); amplification of esterase genes (organophosphorus and carbamate insecticides); mutations linked genetically to a sodium channel gene (DDT and pyrethroid insecticides); and yet uncharacterized mutations leading to the up-regulation of detoxification enzymes, such as cytochrome P450 and glutathione S-transferases (many classes of insecticides). In several cases, the selection of a precisely homologous mutation has been observed in different insect species.
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PMID:Molecular biology of insecticide resistance. 859 50

This review surveys the use of capillary electrophoresis for the analysis of cardiovascular drugs. Each section presents examples of separations according to the class of the cardiovascular agent. The classes presented are beta-adrenergic antagonists (beta-blockers), acetylcholinesterase inhibitors, angiotensin-converting enzyme inhibitors, dieuretics, alpha-adrenergic antagonists, calcium channel blockers, cardiac glycosides, hypolipidemics (HmG-CoA reductase inhibitors and fibric acid), vasodilators and sodium channel blockers. Examples of the separation modes discussed include capillary electrophoresis, micellar electrokinetic chromatography using many additives (e.g. sodium dodecyl sulfate, cyclodextrins, bile salts, proteins, oligosaccharides) and isotachophoresis.
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PMID:Capillary electrophoresis of cardiovascular drugs. 876 40

Several loci conferring insecticide resistance in the yellow fever mosquito (Aedes aegypti) have previously been mapped by simple recombinational mapping. Here we describe correlation of these resistance phenotypes with molecular gene probes for insecticide target sites by RFLP mapping. The para sodium channel gene homologue and the GABA receptor gene Resistance to dieldrin map to the same genome regions as the DDT/pyrethroid and cyclodiene resistance loci, respectively. Although the acetylcholinesterase (target site of organophosphorus and carbamate insecticides) gene Ace does not map to any known resistance locus, it maps very close to the sex-determining locus. We discuss the possibilities that, if identified, Ace-mediated resistance in A. aegypti will be sex linked or that, as suggested for anopheline mosquitoes, two independent Ace loci may exist, one of which is autosomal. These results support the importance of target site insensitivity as an insecticide resistance mechanism in mosquitoes.
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PMID:Molecular mapping of insecticide resistance genes in the yellow fever mosquito (Aedes aegypti). 941 93

Effects of soman, an irreversible cholinesterase (ChE) inhibitor, on [3H]norepinephrine (NE) release evoked by N-methyl-d-aspartate (NMDA) were studied in rat brain cortical slices. Soman inhibited NMDA-stimulated [3H]NE release in a concentration-dependent manner. This effect was neither reversed by atropine, an antagonist of the muscarinic receptor, nor by d-tubocurarine, an antagonist of the nicotinic receptor. Incubation of the slices with NMDA antagonists, AP5, MK-801, ketamine or magnesium, resulted in inhibitory effects on NMDA-stimulated [3H]NE release. Soman significantly shifted the inhibition curves downward and significant interactions between these chemicals and soman were observed. Glycine potentiated the release of [3H]NE stimulated by NMDA, and soman did not alter this effect of glycine. Soman also inhibited the release of [3H]NE evoked by K+ in a concentration-dependent manner. NMDA-stimulated [3H]NE release was inhibited by tetrodotoxin (TTX), an antagonist of voltage-dependent sodium channels, and a significant interaction between soman and TTX was observed. The [3H]NE release induced by NMDA was dependent on extracellular calcium concentrations and was inhibited by nifedipine, a selective blocker of the L-type voltage-dependent calcium channels (VDCC), or cadmium, a non-specific blocker of VDCC. However, no significant interaction between the effects of soman and calcium, nifedipine, or cadmium was observed. Taken together, the results suggested that: (1) soman has a direct action at non-cholinergic sites; (2) soman may interfere with some of the regulatory sites of the NMDA receptor-ion channel complex; and (3) the voltage-dependent sodium channel, but not VDCC, may be a site of action for soman.
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PMID:Inhibition by soman of NMDA-stimulated [3H]norepinephrine release from rat cortical slices, studies of non-cholinergic effect. 951 77

Nuclei in multinucleated skeletal muscle fibers are capable of expressing different sets of muscle-specific genes depending on their locations within the fiber. Here we test the hypothesis that each nucleus can behave autonomously and responds to signals generated locally on the plasma membrane. We used acetylcholinesterase (AChE) as a marker because its transcripts and protein are concentrated at the neuromuscular and myotendenous junctions. First, we show that tetrodotoxin (TTX) reversibly suppresses accumulation of cell surface AChE clusters, whereas veratridine or scorpion venom (ScVn) increase them. AChE mRNA levels are also regulated by membrane depolarization. We then designed chambered cultures that allow application of sodium channel agonists or antagonists to restricted regions of the myotube surface. When a segment of myotube is exposed to TTX, AChE cluster formation is suppressed only on that region. Conversely, ScVn increases AChE cluster formation only where in contact with the muscle surface. Likewise, both the synthesis and secretion of AChE are shown to be locally regulated. Moreover, using in situ hybridization, we show that the perinuclear accumulation of AChE transcripts also depends on signals that each nucleus receives locally. Thus AChE can be up- and downregulated in adjacent regions of the same myotubes. These results indicate that individual nuclei are responding to locally generated signals for cues regulating gene expression.
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PMID:Local control of acetylcholinesterase gene expression in multinucleated skeletal muscle fibers: individual nuclei respond to signals from the overlying plasma membrane. 1064 96


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