Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Rabbit retinas were isolated and superfused with a physiological medium. Ganglion cell activity was recorded during stimulation with focused light, and receptive fields were mapped. Receptive fields were identical to those found in vivo and did not change during a 6-h incubation. After the receptive field of a ganglion cell had been identified, acetylcholine or related agents were introduced singly or in combination into the medium, and their effect on the cell's spontaneous and light-evoked activity was observed. 2. Ganglion cells with on-center or directionally selective receptive fields were excited when ACh was added to the medium. The response to exogenous ACh was prevented by cholinergic antagonists. 3. These cells' spontaneous activity and response to light were enhanced by anticholinesterase and depressed by cholinergic antagonists. Antagonists varied in their ability to block the light-evoked response, with dihydro-beta-erythroidine the most effective. 4. Thresholds for ACh or the related agents were low, ranging from 1 to 40 muM; their effects were rapidly and completely reversed when the retina was returned to control medium. 5. In retinas incubated in medium containing 20 mM Mg2+ and 0.2 mM Ca2+, ganglion cells lost completely both their spontaneous and light-evoked activity, but retained their ability to generate action potentials in response to elevated K+. Ganglion cell activity rapidly returned to normal when the retina was returned to medium containing normal electrolytes. On-center and directionally selective cells were excited by ACh in retinas where synaptic transmission had been inhibited by 20 mM Mg2+ and 0.2 mM Ca2+. 6. The responses of on-center and directionally selective cells to ACh, to anticholinesterase, and to cholinergic antagonists in control medium indicate that the retina contains one or more synapses using ACh as a neurotransmitter. The response to ACh in retinas exposed to 20 mM Mg2+ and 0.2 mM Ca2+ suggests that at least one such synapse in on the ganglion cell itself. 7. Off-center cells were inhomogenous in their response to ACh. Although some responded just as the other classes of cell, the majority responded quite weakly and a subgroup was encountered which was entirely unaffected by even 1 mM ACh, by levels of physostigmine which inactivate virtually all retinal acetyl-cholinesterase, or by high concentrations of cholinergic antagonists. Only 2 of 20 off-cells tested in the presence of 20 mM Mg2+ and 0.2 mM Ca2+ were excited by ACh. Apparently ACh is not a primary transmitter for most off-cells.
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PMID:Responses to acetylcholine of ganglion cells in an isolated mammalian retina. 99 29

The novel combination of supercritical fluid extraction (SFE) with an enzyme assay system has been used to screen meat products to detect the presence of pesticides. Analytes are collected in water by expanding supercritical carbon dioxide to atmospheric pressure through a restrictor and into an aqueous phase. The solution is then tested for the presence of pesticide residues by enzyme assay. Two experimental approaches have been used. Alachlor-fortified lard and bovine liver were monitored by static SFE coupled with an enzyme immunoassay. SFE of carbofuran-fortified frankfurters was coupled with an enzyme assay based on cholinesterase inhibition. A major benefit of the SFE/enzyme assay technique over conventional screening techniques is that the analyst is not exposed to organic solvents.
J Assoc Off Anal Chem
PMID:Supercritical fluid extraction/enzyme assay: a novel technique to screen for pesticide residues in meat products. 175 8

Ten collaborating laboratories assayed 4 blind duplicate pairs of whole bovine blood for cholinesterase activity. The 4 sample pairs ranged from normal (100%) to severely organo-phosphorus-inhibited (less than 10%) activity. Collaborators also received commercially available human lyophillized serum as an external control and a chromate solution to evaluate spectrophotometer performance. The Ellman kinetic assay was performed on a 1:1000 dilution of the whole blood in pH 8.0 phosphate buffer. The method monitors the increase in absorbance at 412 nm caused by formation of 5-thio-2-nitrobenzoic acid (yellow reaction product). Repeatability standard deviations (RSDr) ranged from 4.30 to 14.2%; reproducibility standard deviations (RSDR) ranged from 6.99 to 19.3%. The lower limit of detection was estimated to be 0.10 mumole/mL/min. The method has been approved interim official first action by AOAC.
J Assoc Off Anal Chem
PMID:Enzymatic-spectrophotometric method for determination of cholinesterase activity in whole blood: collaborative study. 221 85

A simple, sensitive, and rapid method is described for the quantitative estimation of nanogram amounts of methyl parathion (O, O-dimethyl O-p-nitrophenyl phosphorothioate) as methyl paraoxon (O,O-dimethyl O-p-nitrophenyl phosphate) on thin layer chromatograms. Methyl paraoxon is detected by pig liver acetone powder cholinesterase inhibition, using p-nitrobenzenediazoniumfluoroborate as the chromogenic reagent. Commercial pig liver acetone powder is more advantageous than raw liver sources because it is readily available and can be preserved indefinitely. About 0.1 ng methyl parathion can be detected, and amounts from 5 to 50 ng can be quantitatively estimated.
J Assoc Off Anal Chem 1981 Nov
PMID:Thin layer chromatographic determination of methyl parathion as paraoxon by cholinesterase inhibition. 730 52

A simple, sensitive, and rapid colorimetric method is described for determining methyl parathion (O,O-dimethyl-O-p-nitrophenyl phosphorothioate) and methyl paraoxon (O,O-dimethyl-O-p-nitrophenyl phosphate), using p-nitrobenzene diazonium fluoroborate as the chromogenic salt. This colorimetric method is more sensitive than are other colorimetric methods based on non-enzymatic reactions. Pig liver acetone powder cholinesterase was found to be sensitive to methyl parathion. Inhibition can be detected at picogram levels, and 50-80 ng methyl paraoxon and 1-9 micrograms methyl parathion can be estimated.
J Assoc Off Anal Chem 1980 May
PMID:Colorimetric determination of methyl parathion and oxygen analog. 743 41

The operating environment of the service personnel during the Persian Gulf War involved psychological, biological, and chemical elements including exposure to pesticides such as the insect repellent DEET (N,N-diethyl-m-toluamide) and the insecticide chlorpyrifos (O,O-diethyl O-3,5,6-trichloropyridinyl phosphorothioate) and to pyridostigmine bromide (PB,3-dimethylaminocarbonyloxy-N-methylpyridinium bromide) that was administered as a prophylactic agent against possible nerve gas attack. The present study was designed to determine the toxicity produced by individual or coexposure of hens 5 days/week for 2 months to 5 mg PB/kg/day in water, by gavage; 500 mg DEET/kg/day, neat, sc; and 10 mg chlorpyrifos kg/day in corn oil, sc. Coexposure to various binary treatments produced greater neurotoxicity than that caused by individual exposures and was characterized by severe neurologic deficit and neuropathological alterations. Also, neurotoxicity was further enhanced following concurrent administration of the three chemicals. Severe inhibition of plasma butyrylcholinesterase (BuChE) activity was produced in hens treated with PB (activity 17% of control) compared to those treated with chlorpyrifos (activity 51% of control) or DEET (activity 83% of control). BuChE inhibition was further increased in binary and tertiary treatment groups compared to individual treatment groups. In contrast, a significant inhibition of brain acetylcholinesterase (AChE) was produced in hens administered chlorpyrifos alone (activity 67% of control), while those given chlorpyrifos in combination with other compounds exhibited a significant inhibition of brain AChE activity ranging from 43 to 76%. Brain neurotoxicity target esterase (NTE) was not inhibited in any of the individual treatment groups or PB/DEET, but was significantly inhibited and had activity expressed as a percentage of control in groups administered combined chlorpyrifos with PB of 73% or DEET of 74% and in the tertiary treatment group of 71%. We hypothesize that test compounds may compete for xenobiotic metabolizing enzymes in the liver and blood and may also compromise the integrity of the blood-brain barrier, leading to an increase in their "effective concentrations" in the nervous system to levels equivalent to the toxic doses of individual compounds. This is consistent with the present observation of increases in (1) the inhibition of brain AChE and NTE, (2) the extent of neurologic dysfunction, and (3) the severity and frequency of neuropathologic lesions in the combined treatment groups compared to those administered individual compounds.
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PMID:Increased neurotoxicity following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos. 895 50

Previously Haley et al. described six possible syndromes identified by factor analysis of symptoms in Gulf War veterans and demonstrated that veterans with these symptom complexes were more neurologically impaired than age-sex-education-matched well controls. They also uncovered strong associations (relative risks 4-8) suggesting that these symptom complexes were related to wartime exposure to combinations of organophosphate pesticides, chemical nerve agents, high concentration DEET insect repellant, and symptoms of advanced acute toxicity after taking pyridostigmine. Here we have shown that compared to controls, ill veterans with the neurologic symptom complexes were more likely to have the R allele (heterozygous QR or homozygous R) than to be homozygous Q for the paraoxonase/arylesterase 1 (PON1) gene. Moreover, low activity of the PON1 type Q (Gln192, formerly designated type A) arylesterase allozyme distinguished ill veterans from controls better than just the PON1 genotype or the activity levels of the type R (Arg192, formerly designated type B) arylesterase allozyme, total arylesterase, total paraoxonase, or butyrylcholinesterase. A history of advanced acute toxicity after taking pyridostigmine was also correlated with low PON1 type Q arylesterase activity. Type Q is the allozyme of paraoxonase/arylesterase that most efficiently hydrolyzes several organophosphates including sarin, soman, and diazinon. These findings further support the proposal that neurologic symptoms in some Gulf War veterans were caused by environmental chemical exposures.
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PMID:Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. 1037 7

Acute lethal interactions have been previously described between a cholinesterase (ChE) inhibitor, pyridostigmine bromide (PB), and the insect repellent, N,N-diethyl-m-toluamide (DEET). The mechanism of toxic interaction between these agents is unknown. Alterations in membrane permeability caused by DEET could facilitate or enhance absorption, or alter the distribution of peripherally restricted PB, causing increased inhibition of ChE at a given dose. Studies were conducted to investigate PB-induced ChE inhibition in the presence of DEET. Rats received ip injections of PB (1, 2, or 3 mg/kg), DEET (200 mg/kg), or PB + DEET at doses that potentiated acute lethality. ChE activity was measured in heart, diaphragm, blood, whole brain, or specific brain areas using a modified spectrophotometric assay. DEET did not alter PB-induced inhibition of ChE activity in rat diaphragm, heart, or blood. Administration of DEET alone had no effect on ChE activity. PB alone did not inhibit ChE in whole brain, but PB (3 mg/kg) + DEET (200 mg/kg) caused significant inhibition of whole brain ChE activity to approximately 60% of controls. In specific brain areas, (cortex, cerebellum, medulla, hypothalamus, hippocampus, midbrain, and striatum) PB alone did not inhibit ChE activity. PB (3 mg/kg) + DEET (200 mg/kg) reduced ChE activity to approximately 65-75% of controls in each brain area, but those results were not statistically significant. In conclusion, DEET did not alter PB-induced inhibition of ChE activity in the periphery. While DEET may have facilitated the access of PB into the CNS at high doses, it is doubtful that the resulting minor reduction in ChE activity would have resulted in death. It is unlikely that the lethal interaction between PB and DEET is mediated through a cholinergic effect resulting from increased inhibition of ChE.
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PMID:Acute effects of an insect repellent, N,N-diethyl-m-toluamide, on cholinesterase inhibition induced by pyridostigmine bromide in rats. 1082 6

Since their return from Persian Gulf War (PGW), many veterans have complained of symptoms including muscle and joint pain, ataxia, chronic fatigue, headache, and difficulty with concentration. The causes of the symptoms remain unknown. Because these veterans were exposed to a combination of chemicals including pyridostigmine bromide (PB), DEET, and permethrin, we investigated the effects of these agents, alone and in combination, on the sensorimotor behavior and central cholinergic system of rats. Male Sprague-Dawley rats (200-250 gm) were treated with DEET (40 mg/kg, dermal) or permethrin (0.13 mg/kg, dermal), alone and in combination with PB (1.3 mg/kg, oral, last 15 days only), for 45 days. Sensorimotor ability was assessed by a battery of behavioral tests that included beam-walk score, beam-walk time, incline plane performance, and forepaw grip on days 30 and 45 following the treatment. On day 45 the animals were sacrificed, and plasma and CNS cholinesterase, and brain choline acetyl transferase, muscarinic and nicotinic acetylcholine receptors were evaluated. Animals treated with PB, alone or in combination with DEET and permethrin, showed a significant deficit in beam-walk score as well as beam-walk time as compared with controls. Treatment with either DEET or permethrin, alone or in combination with each other, did not have a significant effect on beam-walk score. All chemicals, alone or in combination, resulted in a significant impairment in incline plane testing on days 30 and 45 following treatment. Treatment with PB, DEET, or permethrin alone did not have any inhibitory effect on plasma or brain cholinesterase activities, except that PB alone caused moderate inhibition in midbrain acetylcholinesterase (AChE) activity. Treatment with permethrin alone caused significant increase in cortical and cerebellar AChE activity. A combination of DEET and permethrin or PB and DEET led to significant decrease in AChE activity in brainstem and midbrain and brainstem, respectively. A significant decrease in brainstem AChE activity was observed following combined exposure to PB and permethrin. Coexposure with PB, DEET, and permethrin resulted in significant inhibition in AChE in brainstem and midbrain. No effect was observed on choline acetyl transferase activity in brainstem or cortex, except combined exposure to PB, DEET, and permethrin caused a slight but significant increase in cortical choline acetyltransferase activity. Treatment with PB, DEET, and permethrin alone caused a significant increase in ligand binding for m2 muscarinic acetylcholine receptor (mAChR) in the cortex. Coexposure to PB, DEET, and permethrin did not have any effect over that of PB-induced increase in ligand binding. There was no significant change in ligand binding for nicotinic acetylcholine receptor (nAChR) associated with treatment with the chemical alone; a combination of PB and DEET or coexposure with PB, DEET, and permethrin caused a significant increase in nAChR ligand binding in the cortex. Thus, these results suggest that exposure to physiologically relevant doses of PB, DEET, and permethrin, alone or in combination, leads to neurobehavioral deficits and region-specific alterations in AChE and acetylcholine receptors.
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PMID:Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin, alone and in combination. 1215 49

The acute lethal interaction that occurs in rodents when high doses of a peripherally restricted cholinesterase inhibitor, pyridostigmine bromide (PB), and the insect repellent N, N-diethyl-m-toluamide (DEET) are combined was first described during studies of chemical mixtures that were targeted as potential causative agents of Gulf War illnesses. This study was intended to provide insight into possible mechanisms of that lethal interaction. Following a single intraperitoneal injection of PB (2 mg/kg) and/or DEET (300 or 500 mg/kg), respiratory activity was measured in conscious freely moving rats using whole-body plethysmography. Cardiovascular function was also monitored simultaneously through an arterial catheter. PB (2 mg/kg) given alone stimulated respiration and increased blood pressure. Arterial pH levels were decreased, whereas pO(2) and pCO(2) remained at control levels. Administration of DEET (300 mg/kg) alone increased tidal volume and decreased blood pressure. Blood gases and pH levels were unaltered. A higher dose of DEET (500 mg/kg) also decreased respiratory and heart rate. Coadministration of PB (2 mg/kg) and DEET (300 mg/kg) increased tidal volume, decreased arterial pH, and elevated pCO(2). Heart rate and blood pressure declined progressively after drug coadministration. Pretreatment with atropine methyl nitrate (AMN), a peripherally selective competitive antagonist at nicotinic and muscarinic receptor sites, reduced the individual effects of PB or DEET, and significantly increased survival after coexposure to these agents. Although changes in respiratory function may have contributed to the lethal interaction, it was concluded that the primary cause of death was circulatory failure.
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PMID:Cardiorespiratory effects following acute exposure to pyridostigmine bromide and/or N,N-diethyl-m-toluamide (DEET) in rats. 1217 30


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