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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of direct intrastriatal injection of three organophosphate cholinesterase inhibitors, DFP (diisopropylphosphorofluoridate), soman (pinacolyl methylphosphonofluoridate) and sarin (isopropyl methylphosphonofluoridate) has been studied on locomotor activity in the rat. The degree of ChE inhibition has been monitored in the striatum, as well as in surrounding brain areas and blood, in order to verify the selectivity of the treatment and rule out effects attributable to actions in these areas and/or the periphery. It has been determined that while enzyme activity is inhibited in the striatum by all three compounds, only DFP significantly reduces locomotor activity at doses that produce no other observable behavioral deficits, or significant leakage into the periphery. Behavioral recovery occurs before enzyme activity returns to control levels. Possible contributions of DFP's action on other neurotransmitters and on ChE in other brain areas to the inhibition of locomotor activity are discussed.
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PMID:Dissociation of locomotor depression and ChE activity after DFP, soman and sarin. 371 85

Inhibition of four acetylcholinesterases (AChE) and a butyrylcholinesterase (BuChE) by 3-(2,3-dihydro-2,2-dimethyl-benzofuran-'7-yl)-5-methoxy-1,3,4-oxadiaz ol-2(3H)-one (DBOX) and 3-(2-methoxyphenyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (MPOX) was measured by the Ellman spectrophotometric method. Both oxadiazolidinones inhibited AChE and BuChE irreversibly and with quasi first order kinetics. DBOX was 2-3 orders of magnitude more potent than MPOX. Housefly brain AChE and horse serum BuChE were more sensitive than AChEs of red blood cells or eel and Torpedo electric organs. Aldicarb, a carbamate anticholinesterase, which protected Torpedo AChE against irreversible phosphorylation by DFP, also protected it against irreversible inhibition by DBOX and MPOX. It is suggested that the nonesteratic oxadiazolidinones are converted to carbanillates on the surface of the enzyme, then acylate the active site of ChEs, producing carbanillated enzymes. At higher concentrations, the two oxadiazolidinones also affected the specific binding of (125I) alpha-bungarotoxin (alpha-BGT) and [3H]perhydrohistrionicotoxin (H12-HTX) to Torpedo nicotinic ACh-receptors, but did not affect the specific binding of [3H]quinuclidinyl benzilate (QNB) to rat brain muscarinic ACh-receptors.
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PMID:Oxadiazolidinones: irreversible inhibition of cholinesterases and effects on acetylcholine receptors. 382 52

This report describes the distribution of histochemically identified 'non-specific' cholinesterase (ChE)-containing neurons in the dorsal thalamus of the rat. Juvenile or young adult Long-Evans or Sprague-Dawley rats were sacrificed by formalin perfusion. Some animals received systemic injections of 1.5-2.0 mg/kg DFP 4-24 h prior to sacrifice. Separate series of 50 micron frozen sections were processed for cholinesterase histochemistry using acetylthiocholine, butyrylthiocholine, or propionylthiocholine as substrates. Adjacent sections processed with each of the 3 substrates allowed comparison of the distributions of neurons containing the histochemical reaction products. Neurons containing moderate to high concentrations of ChE reaction product were found in 3 distinct regions of the dorsal thalamus. First, neurons staining intensely for ChE were found in a cluster that corresponds to the thalamic reuniens nucleus. Second, a cluster of neurons staining intensely for ChE was found in a region that included the lateral part of the central lateral nucleus and extended laterally into the ventral-lateral part of the lateral dorsal nucleus. Third, moderate ChE staining was observed in the neurons of the anterior dorsal nucleus. Of these regions, only the anterior dorsal nucleus shows moderate to high levels of acetylcholinesterase. The function of ChE in normal brain function is unknown. It is particularly interesting, however, that the thalamic nuclei containing ChE-positive neurons send thalamocortical projections to the medial limbic cortex, including cingulate, retrosplenial and subicular cortices.
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PMID:Distribution of 'non-specific' cholinesterase-containing neurons in the dorsal thalamus of the rat. 395 49

Tri-ortho-tolyl phosphate (TOTP), 360 mg/kg, po, and 0,0'-diisopropyl phosphorofluoridate (DFP), 1 mg/kg sc, were administered to adult White Leghorn chickens 24 hr after they were placed on diets containing 0 to 300 ppm corticosterone. Supplemented diets were continued until clinical signs and lesions of delayed neuropathy appeared. Although low concentrations (less than or equal to 50 ppm) of corticosterone had beneficial effects on TOTP-induced neuropathy, greater than or equal to 200 ppm exacerbated clinical signs in chickens given either TOTP or DFP. Neurotoxic esterase activities 24 hr after TOTP or DFP were less than 20% of values measured in chickens not given organophosphorous compounds. Chickens given 200 ppm corticosterone without TOTP or DFP had significantly elevated activity of plasma cholinesterase and significantly inhibited activity of liver carboxylesterase. Degenerating myelinated fibers were also evident in distal levels of the peripheral nerves of chickens given TOTP or DFP.
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PMID:Dose-related beneficial and adverse effects of dietary corticosterone on organophosphorus-induced delayed neuropathy in chickens. 396 13

1. The effects of intravenous infusions of suxamethonium on the twitch tension of the indirectly stimulated tibialis and gastrocnemius muscles of anaesthetized cats were recorded. From these data the infusion rate giving a 50% reduction in twitch tension after 15 min (IR50), was calculated.2. Marked inhibition of cholinesterase activity in plasma with less inhibition of cholinesterase activity in tissues, obtained by repeatedly withdrawing blood samples, incubating them with DFP and reinjecting them, had only a small effect on the IR50 of suxamethonium.3. Injection of iso-OMPA produced marked inhibition of cholinesterase activity in plasma and tissues, and lowered the IR50 to 10% of that in controls. The IR50 in cats treated with iso-OMPA could be restored to normal only by raising the suxamethonium hydrolysing capacity of plasma 10-50 times above normal by the intravenous injection of purified cholinesterase of human plasma.4. Exchange blood transfusion between normal cats and cats treated with iso-OMPA failed to affect the IR50 of suxamethonium in either of the two.5. It is concluded that in cats, unlike in man, the effectiveness of suxamethonium is not determined by the cholinesterase activity in plasma but by the cholinesterase activity in tissue. The role in this of cholinesterase at the neuromuscular junction and other sites is discussed.
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PMID:Relative importance of the enzymic hydrolysis of suxamethonium in plasma and tissues: studies in cats. 433 3

Cholinesterase inhibitors that can pass the blood-brain barrier produce hypothermia when injected intravenously in just sublethal doses. From a comparison of the hypothermia-reducing effects of five cholinesterase-reactivating oximes when injected intraperitoneally or subarachnoidally into rats pretreated with DFP or soman it was possible to distinguish central and peripheral actions of the oximes. The comparative efficacy of the five oximes and the effectiveness of cholinesterase inhibitors in producing hypothermia in other animal species, including man, are discussed.
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PMID:The anticholinesterase hypothermia in the rat: its practical application in the study of the central effectiveness of oximes. 531 45

Several N-allyl derivatives of 1-phenylcyclohexylamine (PCA) were prepared, and their pharmacology was briefly characterized. The mono- and diallyl derivatives had phencyclidine-like activities in mice but were less potent behaviorally than phencyclidine (PCP). None were PCP antagonists. In vitro these compounds were competitive inhibitors of butyrylcholinesterase (BChE) and protected against inhibition by DFP. In addition, these agents displaced tritiated N-methyl-4-piperidyl benzilate from mouse-brain homogenates and inhibited the effects of acetylcholine on isolated guinea pig ileum. None of these in vitro effects correlated with their PCP-like behavioral activity in vivo in mice.
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PMID:N-allyl analogues of phencyclidine: chemical synthesis and pharmacological properties. 648 61

The acetylcholinesterase activity of erythrocytes was investigated and compared with cholinesterase activity of the blood plasma in rats exposed to elevated temperature of the environment. The rats were kept in a thermic chamber with regulated temperature, forced air flow and controlled moisture of 55-19%. The applied temperatures were 21 degrees C (control) and 28 degrees C or 37 degrees C. The rats were exposed once for 3, 6, 12 or 24 hours and repeatedly for six successive days, for six hours each day. Experiments were also performed to find whether previous exposure of the rats to raised temperature "sensities" acetylcholinesterase to the action of typical cholinesterases inhibitor (DFP). Arrhenius plots were determined for erythrocyte acetylcholinesterase of rats subjected for 6 hours to raised temperature. It was found that the activities of both enzymes undergo only slight changes in dependence on the temperature applied and the time of exposure. More pronounced changes in this activity were observed when the rats were subjected to 37 degrees C. This may have been connected with disturbance of the lipoprotein structure and with an increase of osmotic fragility of the erythrocytes. It was also noted that earlier exposure of the animals to raised environmental temperature "sensitises" the acetylcholinesterase of the erythrocytes to the action of the organophosphorus inhibitor in vivo.
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PMID:Activity of rat blood cholinesterases following exposure of the animals to increased environmental temperature. 653 Sep 50

The effect of chronic administration of diisopropylphosphorofluoridate (DFP) on the levels and forms of plasma cholinesterase (ChE), were studied in male Wistar albino rats sacrificed at different time intervals after various schedules of treatment. In particular the inhibition and recovery rate of the enzymatic activity was evaluated for butyrylcholinesterase (BuChE), determined using butyrylthiocholine (BuThCh) as substrate and for acetylcholinesterase (AChE), measured using acetylthiocholine (AcThCh) in the presence of iso-OMPA 0.1 mM. At 1 1/2 and 24 hr after the DFP treatments, BuChE was considerably more depressed than was the case for AChE. Moreover, the recovery of BuChE proceeded more slowly, its activity being restored only seven days after the last treatment, while the recovery of AChE was completed 72 hr after the end of the treatments. Plasma molecular forms were separated by polyacrylamide gel electrophoresis and were revealed by enzymatic reaction with BuThCh or AcThCh as substrates. By using selective inhibitors, five main molecular forms of BuChE and two of AChE were found to exist in control plasma samples. A differential inhibition and recovery rate was observed among these forms after DFP intoxication. At 1 1/2 hr after the treatments, the BuChE activity was too low to be detected on the gels, but 24 hr thereafter, the quantitative determination of the different forms, performed by scanning densitometry, showed a significant increase of the two faster migrating ones. At the following time intervals, the electrophoretic pattern returned progressively towards normality. The faster migrating forms are therefore probably the first synthesized in the process of recovery of BuChE activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in the levels and forms of rat plasma cholinesterases during chronic diisopropylphosphorofluoridate intoxication. 670 81

The toxicity of trichlorfon (O,O-dimethyl-2,2,2,-trichloro-1-hydroxyethylphosphonate, Dipterex, Dylox), reported to elicit delayed neurotoxicity in man and chickens, was studied by administering single subcutaneous doses of 100 or 300 mg/kg to adult White Leghorn hens. At 24 h posttreatment, the birds were observed for visible signs of neurotoxicity, were euthanized, and samples of blood plasma, brain, and spinal cord (cervical and thoracic regions) were obtained for quantification of cholinesterase and neurotoxic esterase (NTE) activities. In subacute studies, hens were dosed with trichlorfon (100 mg/kg) every 72 h for a total of six doses. Seventy-two hours after the final dose the hens were euthanized, the brains, spinal cords, and distal sciatic nerves were removed for enzymatic and (or) histological examination. Parallel acute and subacute studies were conducted using diisopropyl phosphorofluoridate (DFP), a known neurotoxic agent, at subcutaneous dosages of 1.0 mg/kg. In the acute studies, both DFP and trichlorfon markedly inhibited tissue cholinesterase activities but only DFP elicited a significant inhibition of NTE. In the subacute studies, DFP produced a characteristic central-peripheral distal axonopathy in the 18-day period of study which was confirmed by clinical and morphological evidence and by marked inhibition of neuronal NTE. Trichlorfon caused little or no obvious neurotoxicity, an observation that was supported by minimal morphological changes and impairment of walking ability and no inhibition of brain or spinal cord NTE.
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PMID:An acute and subacute neurotoxicity assessment of trichlorfon. 673 96


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