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 observed equilibrium constant (Kobs) for the reaction of choline acetyltransferase (EC 2.3.1.6) has been determined under physiological conditions. Using sigma and square brackets to indicate total concentrations of all ionic species present: (see article). The value of Kobs has been determined to be 12.3 plus or minus 0.6 at 38 degrees, pH 7.0 and ionic strength 0.25 M. The value at 25 degrees is not significantly different, and the constant has been found to be insensitive to variations in ionic strength (0.03 to 0.375 M), pH (6.5 TO 7.5) OR FREE [Mg-2+] (0 to 5 mM). The Kobs of this reaction reflects the difference between the observed standard free energy change (delta G-oobs) for the hydrolysis of acetylcholine and the delta G-oobs for the hydrolysis of acetyl-CoA. Since the delta G-oobs for the hydrolysis of acetyl-CoA has been previously determined to be minus 8.54 kcal/mol (minus 35.75 kJ/mol under the same physiological conditions, the delta G-oobs for the reaction of acetylcholinesterase (EC 3.1.1.7): (SEE ARTICLE). Can be calculated to be minus 6.99 kcal/mol (minus 29.26 kJ/mol) at pH ionic strength 0.25 M and 38 degrees, taking the standard state of liquid water to have unit activity ([H2O] equals 1). The pKa for acetic acid under the same conditions, has been determined to be 4.60 plus or minus 0.01, allowing the Kobs for the pH-independent reaction (see article). To be calculated to be 3.28 times 10-2 M. Choline and carnitine are chemical analogues. The Kobs for the corresponding reaction of carnitine acetyltransferase (EC 2.3.1.7). (SEE ARTICLE). Under the same physiological conditions of pH (7.0), ionic strength (0.25 M), and temperature (38 degrees) has been determined to be 1.73 plus or minus 0.05, making the delta G-oobs for the hydrolysis of acetylcholine only 1.21 kcal/mol (5.06 kJ) less negative than that for the hydrolysis of acetylcarnitine.
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PMID:Equilibrium constants of the reactions of choline acetyltransferase, carnitine acetyltransferase, and acetylcholinesterase under physiological conditions. 23

The interaction between the reversible cholinesterase inhibitor, physostigmine, and lithium chloride was studied in adult male rats. A combination of lithium plus physostigmine increased lethality more than that caused by either physostigmine or lithium alone. Scopolamine completely reversed this effect. These drug interactions may have clinical significance, since lithium plus cholinesterase inhibitors may be used together in the practice of medicine.
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PMID:Lethal effects of physostigmine plus lithium in rats. 40 35

It has been postulated that behavioral inhibition due to punishment or extinction may be mediated by brain acetylcholine, and drugs which have disinhibitory action are thought to interact with this system. This notion was tested by comparing the effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption. Scopolamine hydrobromide (0.3, 0.5 mg/kg, i.p.), a centrally and peripherally acting antimuscarinic agent and physostigmine sulfate, (0.3 mg/kg, i.p.), a centrally and peripherally acting acetylcholinesterase inhibitor, lowered both non-punished and punishment suppressed water intake and lick rate, whereas their quaternary analogs which primarily act in the periphery, had no significant effect at comparable dose levels. Scopolamine and physostigmine suppressed punished water consumption at lower dose levels than nonpunished intake. In contrast, chlordiazepoxide (5.0, 10.0, 20.0 mg/kg, i.p.) enhanced punished as well as non-punished water intake. In a further experiment comparing punishment and extinction suppression, scopolamine and physostigmine did not affect punished or extinguished water intake; chlordiazepoxide (5.0, 10.0, 20.0 mg/kg) reliably increased punished, but not extinguished licking on the water nozzle. These results suggest (1) that scopolamine and chlordiazepoxide do not act via a common mechanism, and (2) that punishment and extinction suppression are not a pharmacological entity.
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PMID:Effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption in rats. 116 84

The effects of cholinesterase inhibitors, cholinergic agonists, dopaminergic agonists and dopaminergic antagonists on the hyperactivity produced by the muscarinic cholinergic antagonist scopolamine were evaluated in mice. Scopolamine (0.3-10 mg/kg) produced a dose-related increase in locomotor activity, with a peak effect at 3.0 mg/kg. The cholinesterase inhibitor physostigmine (0.03-0.175 mg/kg) was without effect on locomotor activity when administered alone, whereas the cholinesterase inhibitor tetrahydroaminoacridine hydrate (0.3-10 mg/kg) decreased locomotor activity. Both physostigmine and tetrahydroaminoacridine hydrate attenuated the effects of scopolamine. Administered alone, the cholinergic agonists oxotremorine (0.01-0.3 mg/kg) and RS86 (0.1-3.0 mg/kg) produced dose-related decreases in locomotor activity, whereas pilocarpine (0.3-10 mg/kg) had no effect on locomotor activity. None of these three muscarinic agonists significantly attenuated the hyperactivity produced by scopolamine. Administered alone, the dopaminergic agonists quinpirole (0.003-0.1 mg/kg), S-(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine (0.3-10 mg/kg) and SKF 38393 (8-64 mg/kg) had no significant effect on activity, whereas apomorphine (0.3-10 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) increased activity. Quinpirole, apomorphine and S-(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine produced dose-related reversals of the increases in locomotor activity produced by scopolamine. The hyperactivity effects of d-amphetamine were approximately additive with scopolamine, whereas SKF 38393 did not significantly affect scopolamine. The mixed D1/D2 dopaminergic antagonist haloperidol (0.003-3.0 mg/kg) and the selective D1 antagonist SCH 23390 (0.01-0.3 mg/kg) produced dose-related decreases in locomotor activity when administered alone, and also produced dose-related reversals of the hyperactivity produced by scopolamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of the effects of cholinergic and dopaminergic agents on scopolamine-induced hyperactivity in mice. 224 41

The purpose of this study was to describe changes in the neuromuscular junction of rabbit sartorius muscle after shock by superior mesenteric artery occlusion in 18 rabbits. The results revealed that the numeric and volume densities of the acetylcholine (Ach) vesicles of the sartorius neuromuscular junction were decreased during shock when compared by electron microscopy with normal subjects (p less than .001). We also discovered that the release of lysosomes from hepatic cells, erythrocyte acetylcholinesterase (AchE) activity, and hepatic ATP values decreased during shock. Both scopolamine (0.023 mg/kg) and verapamil (0.74 mg/kg) blocked the release of Ach vesicles and lysosomes, and increased hepatic ATP values. Scopolamine also increased AchE activity. This study shows that the parasympathetic activation plays an important role in mesenteric artery occlusion shock.
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PMID:Morphometric study of neuromuscular junction in rabbits subjected to shock by superior mesenteric artery occlusion. 229 15

This experiment examined the effects of repeated exposure to diisopropylfluorophosphate (DFP), an organophosphate anticholinesterase, on the retention and reversal of a visual discrimination and on the number of muscarinic receptors in the brain. Rats were trained in a serial reversal procedure. After achieving stable performance, the rats were divided into two groups. One group received repeated injections of DFP, the other group received injections. To determine whether DFP-treated rats would be more sensitive than normal rats to stresses on the cholinergic system, each rat was injected with saline or one of three doses of scopolamine, a muscarinic receptor blocker, prior to testing on every 6th day. DFP alone caused no impairment in performance. Scopolamine produced a greater impairment in DFP-treated rats than in control rats. Similar results were obtained in a second behavioral task, match-to-sample in a water maze, using the same DFP treatment protocol and only one dose of scopolamine. The number of muscarinic receptors and acetylcholinesterase activity levels were reduced on the 2nd and 15th day after the end of DFP treatment. These results demonstrate that although repeated exposure to organophosphate anticholinesterases may not alter discrimination behavior directly, it may compromise the central nervous system so that it cannot react normally when challenged.
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PMID:Repeated exposure to diisopropylfluorophosphate (DFP) produces increased sensitivity to cholinergic antagonists in discrimination retention and reversal. 230 15

Complex accelerative stimuli can induce pica in rats as well as the treatment with poisons, which means eating of non-nutritive substances such as kaolin, in proportion to the severity of their sickness. For the purpose of using pica as an index of motion sickness in rats, we examined what kind of rotation was effective for inducing pica in rats with or without normal bilateral labyrinth functions. Clinically potent anti-motion sickness drugs, such as scopolamine, methamphetamine, diphenhydramine, were examined in reducing rotation-induced pica in rats. Rats ate more kaolin after double rotation with continuously changing acceleration, than after single rotation. Both the animals treated with anti-motion sickness drugs or labyrinthectomy ate less kaolin even after double rotation. Since the physiological and pharmacological mechanisms for inducing pica in rats were similar with those of motion sickness in humans, pica in rats should be an acceptable index of their motion sickness. In order to study neural mechanisms of motion sickness in rats, we examined the effects of an anti-cholinergic as a potent anti-motion sickness drug and cholinergics as an antagonistic drug treated during the 4th-7th day of rotation on both habituation to double rotation within daily rotations for 10-11 days, using pica as an index of motion sickness. Rats were separated into three groups according to their initial susceptibility, and rats with low susceptibility were omitted in these experiments. Scopolamine (TTS-scopolamine) as an anticholinergic facilitated habituation to motion, especially in rats with moderate susceptibility. Treatment of physostigmine suppressed residual habituation to motion sickness in rats, especially with moderate susceptibility, though neostigmine, peripherally acting anti-cholinesterase, had no effect. These results suggested that centrally acting acetylcholine play an important role in suppressing habituation of motion sickness. In conclusion, rats should be a convenient model for studying for motion sickness, as we examined one of the neural mechanisms in motion sickness using pica as an index.
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PMID:[Animal model of motion sickness in rats]. 258 11

The effect of scopolamine and a cholinesterase inhibitor on long-term potentiation (LTP) of population spikes was studied in a guinea pig hippocampal slice preparation. After brief application of each drug (10 min), LTP in CA1 and CA3 was induced by tetanus stimulation delivered to commissural/associational fibers and mossy fibers, respectively. Scopolamine at concentration of 10 microM had no effect on LTP in CA1 but significantly suppressed LTP in CA3. The cholinesterase inhibitor, 9-amino-1,2,3,4-tetrahydroacridine-1-ol maleate (HP 029) at concentration of 10 microM significantly enhanced LTP both in CA1 and CA3. These results suggest that the cholinergic system is involved in producing LTP in CA3. Another mechanism of the effect of HP 029 on LTP in CA1 is discussed.
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PMID:Effect of scopolamine and HP 029, a cholinesterase inhibitor, on long-term potentiation in hippocampal slices of the guinea pig. 271 Apr 12

The effects of idebenone, a cerebral metabolic enhancer, on learning and memory impairment in two rat models with central cholinergic or serotonergic dysfunction were investigated using positively reinforced learning tasks. A delayed alternation task using a T maze was employed to test the effect of idebenone on short-term memory impairment induced by a cholinergic antagonist, scopolamine. A correct response, defined as a turn toward the arm opposite to that in the forced run, was rewarded with food pellets. Scopolamine (0.2 and 0.5 mg/kg, i.p.) significantly decreased the correct responses to the chance level in the 60-s-delayed alternation task. The scopolamine (0.2 mg/kg, i.p.)-induced impairment of short-term memory was improved by idebenone (3-30 mg/kg, i.p.) or an acetylcholinesterase inhibitor, physostigmine (0.1 and 0.2 mg/kg, i.p.), administered simultaneously. The central serotonergic dysfunction model was produced by giving rats a diet deficient in tryptophan, a precursor of serotonin. The rats fed on a tryptophan-deficient diet (TDD) showed a slower learning process in the operant brightness discrimination task (mult V115 EXT) than did rats fed on a normal diet. Idebenone (60 mg/kg/day) admixed with the TDD decreased the number of lever-pressing responses emitted during the extinction periods. The percentage of correct responses was significantly higher in the idebenone-treated group than in the control TDD group. These results suggest that idebenone may improve both the impairment of short-term memory induced by a decreased cholinergic activity and the retardation of discrimination learning induced by central serotonergic dysfunction.
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PMID:Idebenone improves learning and memory impairment induced by cholinergic or serotonergic dysfunction in rats. 276 40

It has been hypothesized that acetylcholine, choline acetylase and acetylcholinesterase may have an ontogenic and trophic influence in the embryo, and that therefore certain drugs may produce malformations via their effect on the acetylcholine and choline levels in the fetus. Thalidomide and the anticholinergics, scopolamine hydrobromide and orphenadrine hydrochloride, and doxylamine succinate, an antihistamine with secondary anticholinergic action, were administered to pregnant New Zealand White rabbit does from day 8 to day 15 of gestation. Cesarean sections were performed on gestational day 16, the fetuses removed and the acetylcholine and choline contents of the fetuses and placentas were estimated by organic extraction and derivation for injection into a GCMS. These acetylcholine and choline levels were compared with those of the fetuses and placentas of the control animals mated with the same buck on the same day as the treated animals. Thalidomide (50 mg/kg) did not affect acetylcholine or choline levels in the fetuses or the placentas obtained from the treated animal. Scopolamine (approximately 100 micrograms/kg) reduced the choline level in the placenta and fetus but not the acetylcholine levels. Orphenadrine (approximately 24 mg/kg) reduced acetylcholine and choline levels in the fetus and choline levels in the placenta. Doxylamine succinate (10 mg/kg) reduced the acetylcholine levels in the fetus and the choline levels in the placenta. The placenta is a fetal organ and the significance of acetylcholine production by the placenta is as yet unknown. The reduction in acetylcholine levels in the fetus exposed to drugs with an anticholinergic action may be of significance in the production of malformations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetylcholine and choline levels in rabbit fetuses exposed to anticholinergics. 350 93


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