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 mouse liver microsomal mixed-function oxidase system converts several phosphorothiolate pesticides with S-ethyl, S-propyl, or S-butyl groups to more potent inhibitors of acetylcholinesterase. This activation is stereospecific for the chiral isomers of O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothiolate (profenofos insecticide); the more toxic (-) isomer becomes a 34-fold better inhibitor of acetylcholinesterase in vitro, whereas the less toxic (+) isomer is deactivated by a factor of 2. Prior treatment of the microsomes with piperonyl butoxide or another mixed-function oxidase inhibitor markedly decreases the activation. Piperonyl butoxide also protects against brain acetylcholinesterase inhibition and cholinergic symptoms in chicks resulting from (-)-profenofos administration, thus establishing the importance of the oxidative bioactivation of S-alkyl phosphorothiolate pesticides in vivo.
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PMID:Oxidative bioactivation of S-alkyl phosphorothiolate pesticides: stereospecificity of profenofos insecticide activation. 684 16

The effect of adrenalectomy (Adx), SKF 525-A, phenobarbital (PB), and diethyl maleate (DEM) on the acute toxicity of fenitrothion was investigated in male rats by assessing the degree of plasma cholinesterase activity. PB, 60 mg/kg/day for 3 days, exerted no protective effect on the toxicity of fenitrothion (100 mg/kg, p.o.) given 24 h after the last injection. In adrenalectomized and SKF 525-A-pretreated rats, the toxicity of fenitrothion was lower than that of the controls. Fenitrothion toxicity was increased by administration of DEM (1 ml/kg), which depletes hepatic glutathione (GSH) levels. In vitro, the rates of fenitrothion decomposition and fenitrooxon formation by microsomes were markedly affected by PB, SKF 525-A and Adx. The decomposition of fenitrooxon by the microsomal fraction and GSH-dependent decomposition of fenitrooxon by the soluble fraction were not affected by PB, SKF 525-A and Adx pretreatment. The GSH-dependent decomposition of fenitrothion and fenitrooxon was increased by addition of GSH to the incubation mixture. The present results indicate that the GSH-dependent metabolic pathway plays an important role in the detoxication of fenitrothion.
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PMID:Effect of adrenalectomy, pretreatment with SKF 525-A, phenobarbital and diethyl maleate on the acute toxicity of fenitrothion in male rats. 686 Jan 45

Rats were pretreated with phenobarbitol [PB (75 mg/kg, IP)] for 3 days and subsequently injected with parathion, an organophosphorous insecticide, which requires microsomal activation for its anticholinesterase effect or with dichlorovos, a cholinesterase (ChE) inhibitor as such. The difference in the mortality and spontaneous regeneration of inhibited plasma ChE by IP administration of the two insecticides was compared. A single dose of 10 mg/kg parathion caused 100% mortality in PB-untreated rats, but effected no mortality in PB-pretreated rats. A lower dose (7.5 mg/kg) of parathion resulted in plasma ChE levels which were 5, 5, 17, and 93% of initial values in PB-untreated rats and 85, 97, and 92% of initial values in PB-pretreated rats at 2-hr, 1-3-, and 5-day periods, respectively. Mortality resulting from single dose of 30 mg/kg dichlorovos was 30% in PB-pretreated, as well as untreated rats. A lower dose of dichlorovs (20 mg/kg) resulted in plasma ChE activity which was 48, 82, 90, and 97% of initial levels in PB-untreated rats, and 60, 100, 100, and 130% in PB-pretreated rats at 2 hr, 1, 3, and 5 day's, respectively. Administration of 2 mg/kg parathion for 3 days did not affect cytochrome P-450 levels in liver microsomes, but administration of 6 mg/kg dichlorovos for 3 days caused greatly lowered levels of liver microsomal cytochrome P-450, resulting from its inactivation to cytochrome P-420. Phenobarbital caused accelerated in vitro ChE regeneration in the case of dichlorovos-inhibited enzyme in the plasma, but not in the case of parathion-inhibited enzyme.
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PMID:Effect of phenobarbitol pretreatment on regeneration of plasma cholinesterase activity inhibited by parathion or dichlorovos. 705 32

The effects of fenitrothion and methylparathion on the activities of cholinesterase and hepatic microsomal monooxygenases were investigated and compared following a single or repeated oral administration of an equimolar and low dose of the insecticides. The activities of cholinesterase in brain and plasma were inhibited equally by the repetitive administration of both insecticides. Aminopyrine N-demethylase activity and cyt.P-450 content were not affected under the same experimental conditions. However, methylparathion, when given repeatedly, inhibited the dearylation and desulfuration of it own. The results may indicate that low dose continuous exposure to methylparathion could cause the depression of its own metabolism in rat.
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PMID:Comparison of the effect of an equimolar and low dose of fenitrothion and methylparathion on their own metabolism in rat liver. 709 8

The reported investigations were carried out on female Wistar rats aged about 6 weeks, weighing 150 g. During 28 days the fats were given daily organophosphates (DFP, DDVP, Chlorfenvinphos, IPO-62, IPO-63, Phospholine) in a dose of 1/10 LD50 subcutaneously. The observations were conducted on groups of 8 rats. The body weight of the animals was noted on the 10th, 20th and 28th day of the experiment. On the 28th day the rats were killed and the activity of acetylcholinesterase (AChE) was determined by the biochemical method of Hestrin in liver homogenate and in the microsomal, mitochondrial and soluble fractions of liver cells. After 28 days of the experiment the body weight of the rats poisoned with these substances amounted to from 80.8% (DFP) to 90.7% (IPO-63) of that in control animals. The AChE activity was also reduced in relation to the control group ranging in the liver homogenate from 49.7% (DFP) to 75.6% (IPO-63), in the microsomal fraction from 33.0% (DFP) to 63.8% (IPO-63), in the mitochondrial fraction from 45.5% (DFP) to 72.9% (IPO-63), and in the soluble fraction from 52.8% (DFP) to 80.5% (DDVP).
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PMID:Acetylcholinesterase activity in several rat liver cell fractions after repeated poisoning with some organophosphates. 723 37

Axolemma-enriched fractions were isolated from the white matter of bovine corpus callosum via a purified preparation of myelinated axons which were osmotically shocked and fractionated on a discontinuous density gradient. Two membrane fractions of differing density were obtained: both were somewhat enriched over white matter whole homogenate in specific activity of acetylcholinesterase and 5'-nucleotidase and maximal binding capacity for saxitoxin. Both membrane fractions contained appreciable amounts of 2', 3'-cyclic nucleotide 3'-phosphohydrolase; the specific activity of antimycin-sensitive NAPH-cytochrome c reductase and cytochrome c oxidase indicated low levels of contamination by microsomal and mitochondrial membrane. The myelin which is concomitantly isolated with the axolemma-enriched fractions has a lipid and protein composition comparable to that of myelin isolated by other procedures. Both axolemma-enriched fractions contain about one half of their dry weight as lipid comprised of approximately 25% cholesterol, 25% galactolipid (cerebrosides and sulfatides in a molar ratio of about 4:1) and 50% phospholipid, mostly choline phosphatides and ethanolamine phospholes in an equimolar ratio. The axolemma fractions are also enriched in ganglioside content relative to the myelin fraction. The polypeptides of the axolemma-enriched fractions range from 20,000 to over 200,000 in molecular weight; the predominant proteins are in the range from 50,000 to 69,000. The most dense axolemma-enriched fraction is over fourfold enriched in glycoprotein content compared with myelin, with at least 10 different molecular-weight classes of glycoproteins as identified by Schiff stain of polyacrylamide gel protein profiles. The differences and similarities in the molecular composition of axolemma-enriched preparations which have been characterized to date are discussed.
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PMID:Composition of axolemma-enriched fractions isolated from bovine CNS myelinated axons. 727 11

Male mice were given the carbamate insecticide propoxur (2-isopropoxy phenyl methylcarbamate; Baygon) in the drinking water at weekly increasing concentrations (from 50 to 2000 ppm), for a period of 6 weeks. At the end of the treatment the LD50 for propoxur was significantly higher in the treated animals as compared with controls. Propoxur-treated animals were also resistant to the hypothermic effect of an acute administration of the same compound. Groups of mice were challenged with the cholinergic agonist carbachol at intervals during the drinking water dosing and at its end. No differences in sensitivity to carbachol acute toxicity were found between control and treated animals. Propoxur-tolerant animals were also not resistant to the hypothermic effect of oxotremorine, another cholinergic agonist. [3H]Quinuclidinyl benzilate ([3H]QNB) binding (a measure of muscarinic receptor density and affinity) in forebrain, hindbrain and ileum never differed in control and treated mice. The possibility that repeated administrations of propoxur induced increased metabolic inactivation was tested by measuring hexobarbital sleeping time and carboxylesterase activity in treated and control mice. No changes in tissue carboxylesterase activities occurred but hexobarbital sleeping time was significantly reduced in propoxur treated animals suggesting an induction of hepatic microsomal enzymes. These results suggest that tolerance to propoxur is not mediated by a decrease of cholinergic receptors, as reported for other acetylcholinesterase inhibitors, but possibly by an enhancement of its metabolism.
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PMID:Tolerance to the carbamate insecticide propoxur. 730 49

A new procedure is described for the preparation of highly purified and stable secretory vesicles from adrenal medulla. Two forms of acetylcholinesterase, a membrane bound form as well as a soluble form, were found within these vesicles. The secretory vesicles, isolated by differential centrifugation, were further purified on a continuous isotonic Percoll gradient. In this way, secretory vesicles were separated from mitochondrial, microsomal and cell membrane contamination. The secretory vesicles recovered from the gradient contained an average of 2.26 mumol adrenaline/mg protein. On incubation for 30 min at 37 degrees C in media differing in ionic strength, pH, Mg2+ and Ca2+ concentration, the vesicles released less than 20% of total adrenaline. Acetylcholinesterase could hardly be detected in the secretory vesicle fraction when assayed in isotonic media. However, in hypotonic media (less than 400 mosmol/kg) or in Triton X-100 (0.2% final concentration) acetylcholinesterase activity was markedly higher. During hypotonic treatment or when secretory vesicles were specifically lyzed with 2 mM Mg2+ and 2 mM ATP, adrenaline as well as part of acetylcholinesterase was released from the vesicular content. On polyacrylamide gel electrophoresis this soluble enzyme exhibited the same electrophoretic mobility as the enzyme released into the perfusate from adrenal glands upon stimulation. In addition to the soluble enzyme a membrane bound form of acetylcholinesterase exists within secretory vesicles, which sediments with the secretory vesicle membranes and exhibits a different electrophoretic mobility compared to the soluble enzyme. It is concluded, that the soluble enzyme found within isolated secretory vesicles is secreted via exocytosis, whilst the membrane-bound form is transported to the cell membrane during this process, contributing to the biogenesis of the cell membrane.
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PMID:Latent acetylcholinesterase in secretory vesicles isolated from adrenal medulla. 731 5

The localization of acetylcholinesterase (AChE) in the optic lobe in the developing chick embryo was studied histochemically and biochemically. The histochemical reaction of AChE increased remarkably between stage 42 and 44 especially in the neuropile. The increase of the biochemical activity of the AChE in the synaptic membrane fraction occurred at a later stage than that in the microsomal fraction. These findings can be interpreted as the result of axonal transport of the enzyme from the synthetic to the synaptic site.
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PMID:The localization of acetylcholinesterase in the optic lobe in the developing chick embryo. 735 16

The acylation of lysophosphatidylcholine by isolated subcellular fractions of guinea-pig cerebral cortex has been determined. The microsomal fraction contained the highest acylation activity, in terms of both specific and total activity. In all particulate fractions, including synaptic plasma membrane and mitochondria, there was a high correlation (correlation coefficient r = 0.90; P less than 0.001) between acylation and the activity of the microsomal enzyme, NADPH-cytochrome c reductase. No correlation existed between acylation and the activities of (Na+ + K+)-ATPase, acetylcholinesterase or succinate dehydrogenase. Acyl-CoA synthetase and lysophosphatidylcholine/acyltransferase, the individual enzymes responsible for acylation were enriched in the microsomal fraction. The activities of both enzymes in subcellular fractions correlated well with those of NADPH-cytochrome c reductase, with the exception that acyl-CoA synthetase activity in the mitochondrial fraction was largely independent of endoplasmic reticulum. Neither synaptic plasma membranes nor mitochondria appeared to possess significant amounts of acyltransferase activity. The results indicate that the acylation of lysophosphatidylcholine is confined to the endoplasmic reticulum, and that activity present in the synaptic plasma membrane or mitochondrial fraction is attributable to microsomal contamination.
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PMID:The acylation of lysophosphatidylcholine by subcellular fractions of guinea-pig cerebral cortex. 737 36


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