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

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that basal forebrain lesions using different excitotoxins produce similar decreases in cortical choline acetyltransferase, but differential effects on memory. However, basal forebrain cholinergic neurons send efferents to the amygdala and cortex. The present studies compared the effects of several excitotoxins on choline acetyltransferase levels in both of these structures. Lesions of the basal forebrain were made in rats by infusing different doses of either alpha-amine-3-hydroxy-5-methyl-4-isoxazole propionic acid, ibotenic acid, quisqualic acid, quinolinic acid or N-methyl-D-aspartic acid and measuring choline acetyltransferase seven days later. All of the excitotoxins exerted a differential response on cholinergic neurons of the basal forebrain projecting to the cortex or amygdala. Quinolinic acid was a more potent neurotoxin to cholinergic neurons innervating the amygdala than those projecting to the cortex. In contrast, quisqualic acid and alpha-amine-3-hydroxy-5-methyl-4-isoxazole were more potent neurotoxins to the cortical projection. alpha-Amine-3-hydroxy-5-methyl-4-isoxazole propionic acid was the most potent excitotoxin for destroying cholinergic neurons innervating either the cortex or amygdala. A parallel neurotoxic response was obtained in the cortex and amygdala following infusion of ibotenic acid or N-methyl-D-aspartic acid with little selectivity for choline acetyltransferase depletion in the cortex or amygdala. Histological analysis of the injection site revealed that acetylcholinesterase-positive neurons were destroyed by the excitotoxins in a dose-dependent manner. Excitotoxins (ibotenic acid, quinolinic acid, N-methyl-D-aspartic acid) that produce the greatest impairments in memory were found to produce the greatest depletion of choline acetyltransferase in the amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Excitotoxic lesions of rat basal forebrain: differential effects on choline acetyltransferase in the cortex and amygdala. 128 23

Division of the mammalian neostriatum into two intermingled compartments called striosomes and matrix has been established by analysis of enzyme activity, neuropeptide distribution, nucleic acid hybridization, and neurotransmitter receptor binding. Striosomes and matrix are distinct with respect to afferent and efferent connections, and these regions provide the potential for modulation and integration of information flow within basal ganglia circuitry. The primary neurotransmitters of corticostriatal afferents are excitatory amino acids, but to date no correlation of excitatory amino acid receptors and striatal compartments has been described. We examined binding to the three pharmacologically distinct ionotropic excitatory amino acid receptors, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and kainate, in human striatum using in vitro receptor autoradiography and compared the binding to striosomes and matrix histochemically defined by acetylcholinesterase activity. Our findings reveal increased binding to N-methyl-D-aspartate receptors and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in matrix relative to striosomes and increased kainate receptor binding in striosomes relative to matrix. These results suggest that afferent input to the two striatal compartments may be mediated by pharmacologically distinct excitatory amino acid receptor subtypes.
...
PMID:Compartmentalization of excitatory amino acid receptors in human striatum. 138 Jan 63

A method is described for reversed-phase HPLC separation of acetylcholine and choline and of their homologues in tissue extracts or perfusion fluids, combined with postcolumn enzymatic derivatization and fluorometric quantification. The separation occurs on a polymeric resin derivatized with hydrophobic moiety and the mobile phase consists of Na2HPO4, 3-(p-hydroxyphenyl)propionic acid and sodium dodecylsulphate; postcolumn enzyme reactor contains immobilized acetylcholinesterase, choline oxidase, and peroxidase. The limits of detection are 1 pmol choline and 3 pmol acetylcholine per sample. The method is free of interferences encountered with electrochemical detection and well suited for non-attended automatic operation.
...
PMID:Sensitive method for HPLC determination of acetylcholine, choline and their analogues using fluorometric detection. 157 98

A death due to ingestion of 2,4-dichlorophenoxyacetic acid (2,4-D), 2-(2-methyl-4-chlorophenoxy) propionic acid (MCPP), and phosphorothioic acid O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl)ester (chlorpyrifos) is reported. The clinical course, dose ingested, and plasma levels of the chemicals were compatible with previous fatalities due to the chlorophenoxyacetic acids. Chlorpyrifos concentrations and tissue cholinesterase and in esterase inhibitions indicated the presence of the organophosphate and its biochemical effect, but few cholinergic signs were observed clinically. Lymphocytic neurotoxic esterase activity was decreased for a limited period of time after ingestion. Postmortem nervous tissue neurotoxic esterase was also decreased. This association has not been demonstrated before in man. HPLC and GC/NPD methods for measuring chlorophenoxy acetic acids and chlorpyrifos, respectively, are presented.
...
PMID:Toxicologic studies in a fatal overdose of 2,4-D, MCPP, and chlorpyrifos. 619 35

The aim of the present study was to clarify the role of the basal forebrain (BF)-cortical cholinergic system in visual attentional function by investigating the effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-induced lesions of the basal forebrain on performance of a five-choice serial reaction time task. AMPA lesions in the present study produced a profound effect on performance of the task, as measured by choice accuracy and correct response latency. This deficit was significantly greater than that observed in earlier studies following ibotenate- or quisqualate-induced lesions of the BF. However, detailed histological and biochemical analysis revealed three rather different BF lesions depending upon the batch of AMPA supplied. In one group of animals (BF/1) the deficits in task performance were substantially greater and longer lasting compared to another group of lesioned animals (BF/2), which showed behavioral recovery several months following the lesion. The former sustained severe pallidal damage in addition to marked reductions in cortical ChAT activity. Support for the attentional nature of these deficits was obtained by the ability to improve task performance in BF/1 lesioned animals by increasing the duration of the visual stimulus and thus reducing the attentional load placed on these animals. In contrast, performance deficits could be reinstated in those animals showing behavioral recovery (BF/2) by reducing the duration of the visual stimulus and thus increasing attentional load. In the second experiment more discrete lesions of the magnocellular cholinergic neurons were made, resulting in extensive reduction of cortical ChAT activity with considerably less neuronal loss from the dorsal pallidum compared to the BF/1 lesion group. Once again, deficits on the task were substantially greater than observed previously following either quisqualate- or ibotenate-induced BF lesions. Furthermore, the cholinergic specificity of these deficits was supported by the attenuation of behavioral impairments following administration of the anti-cholinesterase physostigmine. Taken together with our earlier work, which has failed to demonstrate mnemonic deficits following lesions to the magnocellular neurons of the nucleus basalis of Meynert, these results suggest that the most consistent deficit produced following lesions of the BF-cortical cholinergic system is attentional dysfunction Analogous deficits in visual attention are also seen in patients with Alzheimer's disease, which can also be improved by anti-cholinesterase treatment.
...
PMID:AMPA-induced excitotoxic lesions of the basal forebrain: a significant role for the cortical cholinergic system in attentional function. 751 37

This study was designed to evaluate the prophylactic efficacy of transdermally administered physostigmine (PHY) against soman exposure using guinea-pigs. Transdermal PHY pad (3 cm2 kg-1; 60 micrograms cm-2), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 h before exposure to the organophosphate. At the time of exposure, PHY concentrations in brain and plasma were ca. 3.6 ng g-1 and 4.1 ng ml-1, respectively. Brain and whole blood cholinesterase (ChE) activity was inhibited to 70% and 47% of the original activity, respectively. Transdermal PHY by itself protected up to 70% of the animals exposed to 1.5 LD50 of soman (100% mortality was recorded in the control group). Combining transdermal PHY with Scopoderm provided full protection against 1.5 LD50 of soman (protection of 70% against 3 LD50). When the prophylactic treatment was combined with post-exposure therapy (atropine, 10 mg kg-1; toxogonin, 10 mg kg-1) 1 min after 5 LD50 of soman, protection of 90% of the animals was achieved.
...
PMID:Prophylactic transdermal treatment with physostigmine and scopolamine against soman intoxication in guinea-pigs. 759 94

The present study was undertaken to study the effect of reduced cortical cholinergic activity on gamma-aminobutyric acid (GABA)ergic and glutamatergic mechanisms in cholinoceptive cortical target regions which are assumed to play an important role for realizing cognitive functions. The densities of cortical muscarinic cholinergic receptor subtypes and corresponding receptor genes m1 through m4, N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainate glutamate receptor subtypes as well as GABAA and benzodiazepine receptors were measured in rats 1 week after unilateral ibotenic acid lesion of the nucleus basalis magnocellularis (Nbm) applying quantitative receptor autoradiography and in situ hybridization. Ibotenic acid lesion resulted in a striking loss of acetylcholinesterase (AChE) staining in the lesioned Nbm which is associated with a 60% decrease in AChE staining and a 30% reduction in [3H]hemicholinium-3 binding in frontal and parietal cortical regions as well fore- and hindlimb areas ipsilateral to the lesion, being more prominent in the more rostral cortical regions. M1-muscarinic cholinergic receptor binding was not changed in any of the cortical regions studied 1 week after lesion. M2-muscarinic receptor binding levels are slightly increased in the parietal cortex only. The lesion-induced increase in parietal cortical M2-muscarinic receptor binding is complemented by an increase in the hybridization signal for the corresponding m4-mRNA transcript. In cortical regions displaying a reduced activity of AChE and decreased levels of high-affinity choline uptake sites due to forebrain cholinergic lesion, NMDA receptor binding was markedly reduced in comparison to the unlesioned brain side whereas AMPA and kainate binding has been significantly increased in these regions. Muscimol binding to GABAA receptors was increased in the rostral portions of frontal and parietal cortices as compared with the unlesioned brain side. Binding levels of benzodiazepine receptors were not affected by the lesion in any of the cortical regions studied. The differential changes in glutamate and GABA receptor subtypes following lesion might be regarded as the consequence of a cortical reorganization compensating for the reduced cholinergic presynaptic input. The data further suggest that presynaptic cortical cholinergic deficits might affect both glutamatergic and GABAergic functions with different intensity and different directions.
...
PMID:Ibotenic acid lesion of nucleus basalis magnocellularis differentially affects cholinergic, glutamatergic and GABAergic markers in cortical rat brain regions. 770 21

Unilateral lesions of the nucleus basalis magnocellularis (NBM) produced by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid in rats caused, 8-10 weeks after the lesion, a 94% reduction in cortical acetylcholinesterase fibres and reduced activities of acetylcholinesterase and choline acetyltransferase by 70-80% in the frontal cortex ipsilateral to the lesion. In anaesthetized unlesioned control rats, iontophoretic administration of acetylcholine and carbachol produced atropine-sensitive inhibition and excitation of frontal cortical neurones, effects similar to those produced by electrically stimulating the NBM. The lesion reduced cortical neuronal firing rates but increased the percentage and sensitivity of neurones responding to acetylcholine, the predominant response changing from inhibition to excitation; response duration increased but latency was unaffected. The size of the response of individual neurones to carbachol, but not the percentage of sensitive neurones, was also increased in lesioned animals. The proportion of neurones responding to bicuculline and their individual sensitivities were increased by the lesion, suggesting that the lesion increased GABAergic tone; responses to glutamate were unchanged. The lesion did not affect the proportion of neurones in which acetylcholine modulated neuronal responses but reversed the nature of the modulation to predominantly excitatory; excitation was the predominant response to electrical forepaw stimulation in unlesioned control animals. This suggests a possible interaction between GABAergic and cholinergic mechanisms in selective attention and processing of cognitive information. Acute administration of di-isopropyl fluorophosphate to unlesioned animals significantly increased the number of frontal cortical neurones responding to acetylcholine, without affecting individual neuronal sensitivity or responses to carbachol and glutamate. The similarity of these effects to those of acetylcholine in lesioned animals suggests that the increased sensitivity to acetylcholine in the latter was due to loss of acetylcholinesterase, enabling diffusion of acetylcholine to more distant neurones. However, acetylcholinesterase does not hydrolyse carbachol and therefore it is necessary to postulate a different post-synaptic mechanism to explain the lesion-induced increases in the sensitivities of individual neurones to carbachol and to acetylcholine; interpretation of experimental findings should take these two mechanisms into account.
...
PMID:An iontophoretic study of the effects of alpha-amino-hydroxy-5-methyl-4-isoxazole propionic acid lesions of the nucleus basalis magnocellularis on cholinergic and GABAergic influences on frontal cortex neurones of rats. 791 93

Unilateral S-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) lesions of the nucleus basalis magnocellularis (nbm), which produced persistent and extensive ChAT-positive cell loss within the nbm and depletion of cortical cholinergic markers in the frontal cortex, increased both the number and sensitivity of individual frontal cortical neurones responding to iontophoretic administration of ACh. The lesion also increased the sensitivity of individual neurones to carbachol but the increase in the number of neurones responding to carbachol was transient and had returned to normal 4 weeks after lesion. The sensitivity of individual neurones to glutamate was unchanged by the lesion. The percentage of cortical neurones responding to ACh, but not the sensitivity of individual neurones was restored to the prelesion level, 6-8 weeks after cholinergic transplants to the lesioned frontal cortex; cholinergic transplants to the more distant parietal cortex were only effective after 6 months whereas noncholinergic transplants were ineffective at both time intervals. Cholinergic transplants placed in the frontal cortex 6-8 weeks or 6 months before nbm lesion offered some protection from the effects of the lesion, particularly at 6 months but were ineffective when placed into the parietal cortex. Lesion of the nbm also reduced basal firing rate of spontaneously active neurones and this was not restored by any of the transplants. The results are discussed in the light of quantitative measurements of acetylcholinesterase-positive fibre outgrowth from the transplant into the recording area, which are described in the preceding manuscript [20].
...
PMID:Changes in the sensitivity of frontal cortical neurones to acetylcholine after unilateral lesion of the nucleus basalis with alpha-amino-3-OH-4-isoxozole propionic acid (AMPA): effects of basal forebrain transplants into neocortex. 899 27

We have compared the singlet oxygen-mediated inactivation of acetylcholinesterase (ACE) in solution with the inactivation of ACE on the surface of K562 leukemia cells. In solution, the actions of the singlet-oxygen quenchers, methionine, azide, disodium [N,N'-ethylenebis (5-sulfosalicylideneimminato)]nickelate(II) (Ni-chelate 1) and disodium [(N,N'-2,3-propionic acid)bis(5-sulfosal-icylideneimminato)] nickelate(II) (Ni-chelate 2) could be explained quantitatively by assuming their only mechanism of action was to quench singlet oxygen. The singlet oxygen quenchers, azide, Ni-chelate 1 and Ni-chelate 2, caused smaller inhibitions in the rate of singlet oxygen-mediated inactivation of ACE on K562 cells than ACE in solution. The effects of these quenchers and of deuterium oxide were interpreted using a mathematical model of singlet-oxygen quenching and diffusion to estimate the lifetime of singlet oxygen near the cell surface. The azide quenching data and the deuterium-oxide data gave lifetimes of 0.9 +/- 0.2 microsecond and 0.45 +/- 0.15 microsecond, respectively. The increases in ACE inactivation lifetime caused by the nickel chelates were anomalously large. The unexpectedly large quenching due to the nickel chelates may have been due to a nonuniform distribution of the chelates in the cytoplasm with a large concentration of the chelate near the cell membrane.
...
PMID:Singlet oxygen-mediated inactivation of acetylcholinesterase: a comparison of purified enzyme in solution and enzyme bound to K562 leukemia cells. 915 62


1 2 3 Next >>

---