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

Recent evidence suggests that termination of cholinergic transmission is just one of the many ways in which acetylcholinesterase (AChE) could influence neuronal function. Neuronal AChE can be secreted from several brain regions, while purified AChE possesses several properties (in addition to its cholinesterase activity) that can affect neuronal function, including the abilities to influence certain membrane conductances, enhance excitatory amino acid transmission and hydrolyse peptides. Loss of AChE and its non-classical actions would have a profound effect on brain function in neurodegenerative diseases such as Alzheimer's disease where there is widespread loss of AChE-containing neurons.
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PMID:Secreted acetylcholinesterase: non-classical aspects of a classical enzyme. 128 48

The involvement of the NMDA receptor in the neurotoxicity induced by soman, an organophosphorus compound which irreversibly inhibits cholinesterase, was studied in guinea pigs. The drug MK-801 (0.5, 1 or 5 mg/kg, i.p.) was given as a pretreatment before a convulsant dose of soman or as a posttreatment (30, 100 or 300 micrograms/kg, i.m.) 5 min after the development of soman-induced status epilepticus. Pyridostigmine, atropine and pralidoxime chloride were also given to each subject to counteract the lethality of soman. All subjects that were challenged with soman and given the vehicle for MK-801 (saline) exhibited severe convulsions and electrographic seizure activity. Neuronal necrosis was found in the hippocampus, amygdala, thalamus and the pyriform and cerebral cortices of those subjects surviving for 48 hr. Pretreatment with 0.5 or 1 mg/kg doses of MK-801 did not prevent nor delay the onset of seizure activity but did diminish its intensity and led to its early arrest. At the largest dose (5 mg/kg), MK-801 completely prevented the development of seizure activity and brain damage. Posttreatment with MK-801 prevented, arrested or reduced seizure activity, convulsions and neuronal necrosis in a dose-dependent manner. The NMDA receptor may play a more critical role in the spread and maintenance, rather than the initiation of cholinergically-induced seizure activity.
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PMID:Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by soman. 152 53

An investigation was made on the frog stomach myenteric plexus with 2 different histochemical techniques. Neuronal perikarya were stained with nicotinamide-adenine-dinucleotide-diaphorase (NADHd), while the acetyl-cholinesterase (AChE) staining showed rather the axoarchitectonic arrangement of the frog myenteric plexus. In double-labelled "whole mounts", NADHd-positive cell bodies and AChE-positive nerve processes were revealed. Some of the nerve cells and neuronal processes did not exhibit AChE activity at all. Since glyoxylic acid-induced fluorescence (GIF) was not detected in the myenteric plexus, the presence of catecholamines can be excluded. As a consequence of these observations, we suggest the presence of a non-cholinergic, non-adrenergic intrinsic neuronal system in the frog stomach myenteric plexus, containing purines or peptides as transmitters.
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PMID:Consecutive diaphorase-acetylcholinesterase histochemistry in the myenteric plexus of frog stomach. 250 Aug 25

Acetylcholinesterase-containing neurons were investigated in primary cultures of cerebral cortex. Neuronal cholinesterase staining was essentially totally attributable to acetylcholinesterase based on its pattern of sensitivity to pharmacological inhibitors. The mean percentage of stained neurons in the cultures was 2.17. Stained neurons of all morphologies were detected: however, the majority of the cells possessed bipolar morphology. The stained bipolar neurons were not a homogeneous morphological population.
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PMID:Morphology of acetylcholinesterase-containing neurons in primary cultures of dissociated rat cerebral cortex. 408 6

Several markers of chick neuroretinal differentiation were monitored in vivo and in culture. All increase markedly between 7 and 20 days of embryonic development in vivo. In vitro, endogenous GABA levels decrease almost immediately, while other neuronal markers increase as in vivo for 2 to 5 days before declining (choline acetyltransferase, acetyl cholinesterase, glutamic acid decarboxylase). Neuronal cell surface markers (binding sites for tetanus toxin, alpha-bungarotoxin, muscimol), however, reach maximal levels only after 8 days in vitro. Glial markers such as carbonic anhydrase and hydrocortisone-induced glutamine synthetase activities are also expressed only transiently in culture.
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PMID:Expression of differentiation markers by chick embryo neuroretinal cells in vivo and in culture. 614 Feb 94

In cases of colorectal innervation disturbance the histological and histochemical findings are well placed to classify the morphological state and to indicate to the pediatric surgeon the therapeutic direction. Any limitation of their value results from technical errors, age dependent localization of morphological structures and the subjectivity of the assessment. For this reason a quantitative biochemical investigation of cholinesterase activity in homogenized investigation of cholinesterase activity in homogenized rectal mucosa specimens and resected bowel segments was performed. The biochemical standard value of the AChE-activity amounts up to 3-6 x 10(-7) mol ACh/min/g in healthy test patients and the ratio of specific/unspecific esterases 1.1 to 1.3. The percentage of AChE to the total enzyme activity was 47.5%. The standard distribution of the different globular and asymmetric cholinesterase structures is described by the proportion of the molecular types G1/G2/G4 and A12. These main types determine the biochemical nature of the human rectum. Hypertrophy of cholinergic nerve fibres in aganglionic bowel segments correlates pathobiochemically with the increase of the cholinesterases caused by the high molecular tetramer G4. However, the Hirschsprung's disease could not be differentiated by the percentage of the AChE-activity to the total ChE-activity because of the continuous increase in the BChE in the aganglionic tissue. Neuronal intestinal dysplasias with their main cholinergic nerve fibre hyperplasias are characterized by disturbances of the dualism and interrelation of different cholinesterases. By means of pathogiochemical investigations the subjective factor in the assessment of histochemical states is avoided and the diagnostic accuracy increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitative investigations of acetylcholinesterase activities in colorectal malformations. 774 35

It has been hypothesized that acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are coregulators of the duration of action of acetylcholine in cholinergic neurotransmission, suggesting that BuChE may also have an important role in the brain. To compare the expression of cholinesterases in the human thalamus, the distributions of BuChE and AChE activity were studied by using a modified Karnovsky-Roots method. BuChE activity was present mainly in neurons, whereas AChE activity was present in both neurons and axons. There was intense staining for BuChE or AChE throughout the thalamus, with some nuclei primarily expressing one or the other cholinesterase. BuChE staining was most intense and widespread in neurons in the anteroventral, mediodorsal, ventral, lateral, and pulvinar thalamic nuclei. AChE was predominantly expressed in neurons of the anterodorsal, midline, ventral, intralaminar, and reticular nuclei. Many nuclei contained both cholinesterases. Considering the overall patterns of labeling in the thalamus for the two cholinesterases, there were both complementary and overlapping relationships of BuChE and AChE activity. Neuronal staining in the subthalamic nucleus and hypothalamus was predominantly positive for AChE activity. The distinct distribution of BuChE activity in neurons in the human thalamus is consistent with an important role for this enzyme in neurotransmission in the human nervous system. Furthermore, BuChE activity, like AChE activity, is found in certain thalamic nuclei related to cognitive and behavioral functions. Involvement of thalamic nuclei in diseases of the nervous system such as Alzheimer's disease and schizophrenia suggests that BuChE could be a potential target for therapeutic intervention in these disorders.
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PMID:Differential distribution of butyrylcholinesterase and acetylcholinesterase in the human thalamus. 1281

In spite of intensive investigations, the roles of acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BuChE; EC 3.1.1.8) in the central nervous system (CNS) remain unclear. A role recently proposed for BuChE as an explanation for survival of AChE knockout mice is compensation for AChE activity if it becomes insufficient. Neuronal contribution of both enzymes to the cholinesterase pool in the neuromuscular junction has also been suggested. These proposals imply that BuChE expression follows that of AChE and that, in addition to AChE, BuChE is also expressed in alpha-motor neurons. However, these assumptions have not yet been properly tested. Histochemical approaches to these problems have been hampered by a number of problems that prevent unambiguous interpretation of results. In situ hybridization (ISH) of mRNAs encoding AChE and BuChE, which is the state-of-the-art approach, has not yet been done. Here we describe rapid nonradioactive ISH for the localization of mRNAs encoding AChE and BuChE. Various probes and experimental conditions had been tested to obtain reliable localization. In combination with RT-PCR, ISH revealed that, in rat spinal cord, cells expressing AChE mRNA also express BuChE mRNA but in smaller quantities. alpha-Motor neurons had the highest levels of both mRNAs. Virtual absence of transcripts encoding AChE and BuChE in glia might reflect a discrepancy between mRNA and enzyme levels previously reported for cholinesterases.
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PMID:Localization of mRNAs encoding acetylcholinesterase and butyrylcholinesterase in the rat spinal cord by nonradioactive in situ hybridization. 1462 31

When animals learn hippocampus-dependent associative and spatial tasks such as trace eyeblink conditioning and the water maze, CA1 hippocampal neurons become more excitable as a result of reductions in the post-burst, slow afterhyperpolarization. The calcium-activated potassium current that mediates this afterhyperpolarization is activated by the calcium influx that occurs when a series of action potentials fire and serves as a modulator of neuronal firing frequency. As a result, spike frequency accommodation is also reduced after learning. Neuronal calcium buffering processes change and/or voltage-dependent calcium currents increase during aging; leading to enhancements in the slow afterhyperpolarization, increased spike frequency accommodation and age-associated impairments in learning. We describe a series of studies done to characterize this learning-specific enhancement in intrinsic neuronal excitability and its converse in aging brain. We have also combined behavioral pharmacology and biophysics in experiments demonstrating that compounds that increase neuronal excitability in CA1 pyramidal neurons also enhance learning rate of hippocampus-dependent tasks, especially in aging animals. The studies reviewed here include those using nimodipine, an L-type calcium current blocker that tends to cross the blood-brain barrier; metrifonate, a cholinesterase inhibitor; CI1017, a muscarinic cholinergic agonist; and galantamine, a combined cholinesterase inhibitor and nicotinic agonist. Since aging is the chief risk factor for Alzheimer's disease, a disease that targets the hippocampus and associated brain regions and markedly impairs hippocampus-dependent learning, these compounds have potential use as treatments for this disease. Galantamine has been approved by the USDA for this purpose. Finally, we have extended our studies to the TG2576 transgenic mouse model of Alzheimer's disease (AD), that overproduces amyloid precursor protein (APP) and increases levels of toxic beta-amyloid in the brain. Not only do these mice show deficits in hippocampus-dependent learning as they age, but their hippocampal neurons show a reduced capacity to increase their levels of intrinsic excitability with reductions in the slow afterhyperpolarization after application of the muscarinic agonist carbachol. These TG2576 APP overproducing mice were crossed with BACE1 knockout mice, that do not produce beta-amyloid because cleavage of APP by the beta-site APP cleaving enzyme 1 (BACE1) is a critical step in its formation. Not only was hippocampus-dependent learning rescued in the bigenic TG2576-BACE1 mice, but the capacity of hippocampal neurons to show normal enhancements of intrinsic excitability was restored. The series of studies reviewed here support our hypothesis that enhancement in intrinsic excitability by reductions in calcium-activated potassium currents in hippocampal neurons is an important cellular mechanism for hippocampus-dependent learning.
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PMID:Pharmacological and molecular enhancement of learning in aging and Alzheimer's disease. 1645 91

Sleep disorders and disruptive nocturnal behaviours are commonly reported in people with senile dementia and present both a significant clinical problem and a cause of increased stress for caregivers. Neuronal degeneration of cholinergic Nucleus basalis Meynert (NBM) neurons promote rest-activity disturbance and Sundowning in Alzheimer's disease. NBM neurons modulate the activity of the mainly cholinergic suprachiasmatic nucleus (SCN) and the induction of NONREM sleep. Sundowning might be explained as a syndrome occurring when arousal is to be processed while the neocortex is already turned "off" to (NONREM) sleep. The therapeutic measures should thus primarily be aimed at the stimulation of the circadian system and enforcing "external Zeitgebers". Pharmacologically, application of cholinergic enhancers i.e. cholinesterase inhibitors and melatonin supports and should stabilize the weakened structures.
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PMID:Sundowning and circadian rhythm disorders in dementia. 1732 34


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