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

Rats were trained to press a lever under a multiple Fixed-Ratio 25 Fixed-Interval 50-second schedule of food reinforcement. Subcutaneous injection of soman, 80 micrograms/kg, suppressed responding under both schedules and inhibited acetylcholinesterase (AChE) in the brain. AChE activity in the gastrointestinal tract was not significantly inhibited. In contrast, i.p. injection of either soman (10-40 micrograms/kg), neostigmine (75 micrograms/kg) or DFP (350 micrograms/kg) caused marked suppression of behavior and AChE activity of the gut, without affecting brain AChE. These doses caused marked increases in peristaltic activity and likely caused gastrointestinal spasm. Injection of DFP, 500 micrograms/kg, s.c., inhibited AChE in both the brain and gut. The results indicate that inhibition of AChE in the gastrointestinal tract by certain anticholinesterase agents may be involved in the behavioral effects attributed to these drugs.
 ...
PMID:Inhibition of acetylcholinesterase in the gut inhibits schedule-controlled behavior in the rat. 401 Apr 69

The effect of a single dose of diisopropylfluorophosphate on acetylcholinesterase (AChE) activity was examined in mouse CNS reaggregate cultures. At 17-24 days in culture, reaggregates were treated with 0.6 mg/liter DFP for 15 min. The recovery of AChE activity was examined in culture. After treatment, 5.4 +/- 1.19% of control AChE activity remained. By 24 hr, 31.6 +/- 6.4% of control activity had returned and the recovery of activity was essentially complete by 7 days after treatment. Recovery of AChE activity after DFP treatment required protein synthesis, since there was no recovery in the presence of cycloheximide. After treatment with the reversible inhibitor, physostigmine at 0.5 mg/ml, recovery of AChE activity was complete within 24 hr after treatment. These results indicate that CNS reaggregate cultures not only express differentiated functions of the CNS, but also have the capacity to turn over proteins, and thus may provide a good model system in which to examine mechanisms of toxicity.
 ...
PMID:Recovery of acetylcholinesterase activity after acute organophosphate treatment of CNS reaggregate cultures. 409 72

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.
 ...
PMID:Relative importance of the enzymic hydrolysis of suxamethonium in plasma and tissues: studies in cats. 433 3

1 Cats were anaesthetized with pentobarbitone sodium and atropinized peripherally by intravenous injection of atropine methyl nitrate; the effect was examined of topical bilateral application of dyflos to the ventral surface of the medulla oblongata at a region lateral to the pyramids and caudal to the trapezoid bodies. Dyflos was applied by means of perspex rings; the volume of fluid placed in each ring was 10 mul.2 The topical application of dyflos (1-20 mg/ml) produced a fall in arterial blood pressure without changes in heart rate and, in experiments without artificial ventilation, tachypnoea with dissociation of thoracic and abdominal respiration.3 Atropine methyl nitrate (50 mg/ml) applied topically in the same way as dyflos, prevented or abolished its vasodepressor effect.4 The two reactivators of acetylcholinesterase, obidoxime (100-200 mg/ml) and pralidoxime mesylate (100-200 mg/ml), applied topically in the same way as dyflos, abolished its vasodepressor effect. The reactivator compound 30 (100 mg/ml), also a pyridinium aldoxime, did not have this effect.5 Obidoxime and pralidoxime mesylate also reversed the vasodepression produced by carbachol applied to the ventral surface of the brain stem but not the vasodepression produced by glycine similarly applied.6 The problem is discussed as to whether the reversal of the dyflos and carbachol-induced vasodepression by obidoxime and pralidoxime is due to acetylcholinesterase reactivation by dephosphorylation and decarbamylation respectively, to a central atropine-like action of these compounds or to a combination of both.
 ...
PMID:A central vasodepressor effect of Dyflos. 461 81

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.
 ...
PMID:The anticholinesterase hypothermia in the rat: its practical application in the study of the central effectiveness of oximes. 531 45

Squid nerve contains an enzyme that hydrolyzes the nerve gas Tabun at about one-tenth the rate it hydrolyzes diisopropylphosphorofluoridate (DFP), and at about one-third to one-fourth the rate it hydrolyzes Sarin and Soman. Tabun is a more potent inhibitor of acetylcholinesterase than is DFP, is both lipid-and water-soluble, and penetrates readily into the squid giant axon in its inhibitory form. The failure of Tabun to block or markedly decrease the conducted action potential in the squid axon makes it likely that the blocking of conduction caused by DFP is probably not due to inhibition of acetylcholinesterase. Sub-strate specificity with regard to organophosphate metabolism by squid enzyme has possible implications for the disposal and detoxication of nerve gases in the ocean.
 ...
PMID:Diisopropylphosphorofluoridate and Tabun: enzymatic hydrolysis and nerve function. 557 58

Superfusion of the organophosphorous acetylcholinesterase inhibitor soman (pinacolyl methylphosphonofluoridate; 0.01-25 microM) produced a dose-dependent reduction of extracellularly and intracellularly recorded synaptic responses in the isolated rat superior cervical ganglia at frequencies of orthodromic stimulation that do not normally produce synaptic depression. The magnitude of depression was dependent upon the frequency of stimulation (0.02-1 Hz), was maintained after the removal of soman from the superfusion solution, and recovered by over 65% during periods of inactivity. The depression of synaptic transmission produced by soman was not dependent upon the inhibition of acetylcholinesterase (AChE) activity by this agent. Transmission was increasingly depressed by doses of soman greater than those needed to inactivate all measurable ganglionic AChE activity. Dose-dependent depression of synaptic transmission in soman also occurred after pretreatment with the irreversible AChE inhibitor diisopropylphosphofluoridate (DFP; 100 microM), which inhibited greater than 98% of the AChE activity in the ganglia. Soman produced a decline in the input resistance, resting potential, spike amplitude, and spike threshold and a reduction in the hyperpolarizing afterpotential. Soman-induced depression of synaptic transmission was not due primarily to a blockade of postsynaptic nicotinic receptors. At concentrations of soman which produced significant depression in transmission, ganglionic depolarization produced by bath-applied carbamylcholine (carbachol) was either slightly depressed or facilitated. In the presence of soman, repetitive focal application of acetylcholine or carbachol did not reveal use-dependent desensitization. Muscarinic antagonists, atropine and pirenzepine, protected against the use-dependent depression of synaptic transmission induced by soman. These results suggest that a principal site of action for soman is at the presynaptic terminal and that this site is sensitive to muscarinic receptor blockade.
 ...
PMID:Noncholinesterase actions of an irreversible acetylcholinesterase inhibitor on synaptic transmission and membrane properties in autonomic ganglia. 615 5

The detoxication of organophosphorus compounds by phosphorylphosphatases was studied in primates. Taking into account the distribution of paraoxonase (EC 3.1.1.2) and DFPase (EC 3.8.2.1) in different tissues of the monkey (Macaca mulatta), the total detoxicating capacity for diethyl-p-nitrophenylphosphate (paraoxon, E 600) and diisopropylphosphorofluoridate (DFP) was determined. Acetylcholinesterase (AChE) (EC 3.1.1.7) of human brain was inhibited in vitro by paraoxon and DFP. Using the rate constants of AChE-inhibition and of AChE-synthesis those concentrations of organophosphorus inhibitors were calculated, which in vivo would reduce the steady-state AChE-activity to 20% of normal. This acute ineffective concentration is 7.6 X 10(-8) g/kg for DFP and 2.3 X 10(-8) g/kg for paraoxon. From substrate kinetics of the phosphorylphosphatases the time course of paraoxon and DFP detoxication in primates could be calculated. The time needed by phosphorylphosphatases to reduce a certain dose of an organophosphorus compound to the acute ineffective concentration is referred to as "effective detoxication time". The effective detoxication time (teff) was determined for different concentrations of paraoxon and DFP and was compared with the time needed by these organophosphate concentrations to inhibit AChE-activity to 12.5% of normal (t1/8). The significance of in vitro data for the evaluation of dose limits of organophosphate toxicity in vivo is discussed.
 ...
PMID:[Enzymatic detoxication of organophosphorus insecticides and nerve gases in primates]. 629 13

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.
 ...
PMID:Activity of rat blood cholinesterases following exposure of the animals to increased environmental temperature. 653 Sep 50

The human neostriatum was found to contain large neurons (maximum diameter: 30-40 microns) that stain intensely for acetylcholinesterase (AChE). These neurons are few in number, representing less than 5% of the total striatal neuronal population, and appear uniformly scattered throughout the caudate nucleus and putamen. They are morphologically similar to the AChE-containing neurons disclosed in the striatum of rat, cat and monkey after AChE inhibitor (DFP) pretreatment. In Alzheimer-diseased brains the number, morphological characteristics, and staining intensity of the striatal AChE neurons were found to be unaltered despite a marked loss of AChE cells in the adjoining nucleus basalis. These findings suggest that large intrinsic cholinergic neurons exist in human neostriatum and that these elements, in contrast to those of nucleus basalis, are not affected in Alzheimer's disease.
 ...
PMID:The occurrence of large acetylcholinesterase-containing neurons in human neostriatum as disclosed in normal and Alzheimer-diseased brains. 669 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>