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)

Cholinesterase (ChE) levels (Ellman method) were monitored in 90 subjects (69 males and 21 females) exposed to carbamate and organophosphate pesticides (78 agricultural workers and 12 pesticide vendors). Pre-exposure baseline values of plasma and red blood cell cholinesterase activities were defined for each subject with two blood samples (23 workers) or three blood samples (59 workers) taken almost thirty days after the last exposure. After control of intra-individual variation, 8 subjects with only one pre-exposure value and 13 with a coefficient of variation above 30% were excluded. For the other 59 subjects, the intra-individual variation of erythrocyte ChE (16%) was similar to the inter-individual one (15%), whereas the inter-individual variation of plasma ChE (21%) was higher than the intra-individual one (14%). Laboratory variation for plasma ChE measurements was 8%. Baseline values were analyzed (ANOVA) for sex, age, task and hour and season of sampling. Both erythrocyte and plasma enzymes, corrected for hematocrit, were lower in females. Plasma cholinesterase activity was lower in "re-entry" agricultural workers and in pesticide vendors. Post-exposure cholinesterase activity was measured in 54 workers within a few (1-21) days after last handling. Average relative reduction was 15.2% (95% C.I. = 4.9%-25.5%) in erythrocyte cholinesterase activity and 29.1% (95% C.I. = 18.2%-40.1%) in plasma cholinesterase activity. The one-way variance analysis showed marked plasma ChE reduction in mixers, loaders and appliers (36%, 95% C.I. = 24%-48%) and in parathion handlers (35%, 95% C.I. = 21%-49%. No significant reduction in blood cell cholinesterase activity in relation to task and to pesticide handled was observed. We conclude that the intra-individual variations of the baseline values were higher for three repetitions (88% and 84% of the population were within a variability of less than 30%, for AChE and for ChE respectively) than for two repetitions (91% and 88% of the population were within 30% of variability for AChE and for ChE respectively). The figures show a greater sensitivity of plasma ChE activity in acute exposure, probably due to a poor reliability in detection of erythrocyte ChE by local laboratories. The maximum reduction (38%, 95% C.I. = 22%-53%) in plasma ChE activity was observed within six days of the last exposure in loaders and appliers.
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PMID:[The monitoring of cholinesterases in farm workers and tradesmen exposed to phosphoric esters and carbamates]. 163 Apr 2

The ability of acetylcholinesterase from fetal bovine serum (FBS AChE) to protect against soman, a highly toxic organophosphorus (OP) compound, was tested in rhesus monkeys. Intravenous administration of FBS AChE produced a minimal behavioral effect on the serial probe recognition task, a sensitive test of cognitive function and short-term memory. Pharmacokinetic studies of injected FBS AChE indicated a plasma half-life of 40 hr for FBS AChE in monkeys. Both in vitro and in vivo titration of FBS AChE with soman produced a 1:1 stoichiometry between organophosphate-inhibited FBS AChE and the cumulative dose of the toxic stereoisomers of soman. Administration of FBS AChE protected monkeys against the lethal effects of up to 2.7 LD50 of soman and prevented any signs of organophosphate intoxication, e.g., excessive secretions, respiratory depression, muscle fasciculations, or convulsions. In addition, monkeys pretreated with FBS AChE were devoid of any behavioral incapacitation after soman challenge, as measured by the serial probe recognition task. Compared to the current multicomponent drug treatment against soman, which does not prevent the signs or the behavioral deficits resulting from OP intoxication, use of FBS AChE as a single pretreatment drug provides significantly effective protection against both the lethal and the behavioral effects of soman.
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PMID:Protection of rhesus monkeys against soman and prevention of performance decrement by pretreatment with acetylcholinesterase. 163 92

The anterior major pelvic ganglion (AMPG) of the male guinea-pig has been found to consist of three principal components. The presence of a cholinergic component was determined by the demonstration of cytoplasmic and nerve fibre acetylcholinesterase activity. A noradrenergic component was demonstrated by immunoreactivity (IR) of the catecholamine-synthesising enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) in neuronal perikarya. The AMPG also had a peptidergic component which may or may not sub-classify the cholinergic and noradrenergic components. Neuropeptide Y (NPY)-, vasoactive intestinal peptide (VIP)-, and atrial natriuretic factor (ANF)-immunoreactivities were seen in neuronal perikarya, nerve fibres and nerve terminals/varicosities, while somatostatin (SOM)-IR was restricted to neuronal perikarya. Substance P (SP)-IR was present in a dense network of varicose nerve fibres. However, on a rare occasion SP-IR was observed in neuronal perikarya. Enkephalin (ENK)-IR occurred in a sparsely distributed plexus of varicose nerve fibres. The analysis of adjacent serial sections demonstrated distinct patterns of neuropeptide coexistence in AMPG neurons. NPY-IR was colocalised to a subpopulation of TH-IR neuronal perikarya. NPY-IR was also colocalised with VIP-IR in non-TH-IR neuronal perikarya. VIP-IR occurred together with AChE in particular neuronal perikarya. The relationship between immunoreactive neuronal perikarya and immunoreactive nerve terminals was investigated. SP-IR nerve terminals were closely related to neuronal perikarya exhibiting VIP-, NPY-, or TH-IR. TH-IR neuronal perikarya were also abutted by ENK-IR nerve terminals. VIP- and NPY-immunoreactive neuronal perikarya were abutted by two nerve terminal types: one immunoreactive for VIP, the other for NPY. DBH-IR neuronal perikarya received AChE-positive varicosities while AChE-positive neurons were abutted by DBH-IR varicose nerve fibres. AChE-positive varicosities were also closely related to neuronal perikarya possessing VIP-IR and AChE activity.
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PMID:Specific patterns of immunoreactivity in neuronal elements of the anterior major pelvic ganglion of the male guinea-pig. 168 Aug 42

The present experiments were performed to determine whether the age-related loss of striatal D2 receptors could be localized to a kainic acid-sensitive neuronal population. This neurotoxin selectively destroys intrinsic neurons. Thus, if kainic acid reduced striatal D2 receptor concentrations such that age differences in this parameter were no longer observed, it would be a good indication that the D2 receptors lost through aging are also sensitive to kainic acid. Mature (6 months) and senescent (24 months) rats were stereotaxically, unilaterally injected with 3 micrograms/0.5 microliter kainic acid into the right striatum. Seven days later striatal D2 receptors were assessed with [3H]-spiperone in one group of mature and senescent rats. A second group of mature and senescent unilaterally lesioned rats was anesthetized and perfused. Brains were dissected and processed for striatal cell counts using cresyl violet staining, tyrosine hydroxylase and met-enkephalin using immunocytochemistry, and acetylcholinesterase using histochemistry. Age-related differences in D2-receptor concentrations were observed in intact, but not lesioned, striata. Kainic acid was less effective in reducing D2-receptor concentrations in senescent animals, suggesting that some proportion of the receptors was already lost prior to lesioning. Kainic acid also reduced total neuronal numbers, as well as Met-Enk and AChE positive staining, to approximately the same extent in mature and senescent rats. No age differences were seen in any of the other parameters following kainic acid administration.
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PMID:The deleterious effects of aging and kainic acid may be selective for similar striatal neuronal populations. 168 53

Monoclonal antibodies against human erythrocyte acetylcholinesterase (acetylcholine acetylhydrolase EC 3.1.1.7) have been examined for inhibition of enzyme activity. Of sixteen antibodies analyzed, only one (C1B7) inhibited enzyme activity, indicating selection of an unusual susceptible site. The inhibitory activity of C1B7 was characterized and compared to another inhibitory antibody, AE-2, previously described by Fambrough et al. (Proc. Natl. Acad. Sci. USA 79, 1078, 1982). Maximal demonstrated inhibition was 84% for C1B7 and 72% for AE-2 and antibody inhibition of enzyme activity was equivalent for the reduced and alkylated acetylcholinesterase monomer and the intact dimer. The Ki (stoichiometry of the enzyme-antibody reaction estimated from enzyme kinetics) was 1.0 for C1B7 and 4.8 molecules of antibody per monomer of acetylcholinesterase for AE-2. The antibodies did not compete with one another for binding to acetylcholinesterase, indicating that they have different target epitopes on the enzyme. Antibody binding to the enzyme was not specifically affected by any of the anticholinesterase agents tested: (a) the irreversible esteratic site-directed inhibitor diisopropylfluorophosphate; (b) the reversible active site-directed inhibitors edrophonium, neostigmine, BW284c51, and carbachol; and (c) allosteric site-directed compounds propidium and gallamine. Kinetic analysis of their effects provide evidence that both antibodies decrease the catalytic rate of enzyme activity and have little or no effect on substrate binding.
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PMID:Novel allosteric sites on human erythrocyte acetylcholinesterase identified by two monoclonal antibodies. 168 85

Monoclonal antibody 25B1 generated against diisopropyl phosphorofluoridate inhibited fetal bovine serum acetylcholinesterase has been extensively characterized with respect to its anticholinesterase properties. This antibody demonstrated considerably different properties from previously reported inhibitory antibodies raised against acetylcholinesterase in terms of the degree of inhibition (greater than 98%), the high degree of specificity, and the stability of the antigen-antibody complex. Monoclonal antibody 25B1 appears to be directed against a conformational epitope located in close proximity to the catalytic center of the enzyme and was found to be most suitable for studying the stabilization of the active site of acetylcholinesterase against denaturation by heat or guanidine following phosphorylation by organophosphorus anticholinesterase compounds. This approach allowed the determination of stability rank order of various phosphorylated acetylcholinesterases. Among all the organophosphates tested, the combination of a methyl group and a negatively charged oxygen attached to the P atom, CH3P(O)(O-)-AChE, conferred the greatest protection to the active site of aged or nonaged organophosphoryl conjugates of acetylcholinesterase.
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PMID:Differences in conformational stability between native and phosphorylated acetylcholinesterase as evidenced by a monoclonal antibody. 169 36

Differentiation of individual rhombomeres of the chicken hindbrain directly follows the emergence of primary brain vesicles. Immediately after the constriction of the prosencephalon at HH9, a series of vesicles of decreasing size is established almost simultaneously between HH9 and HH10, including mesencephalon, four preotic (R2-R5) and one postotic (R6/R7) rhombomeres. Thereby, the cranial neural tube is ventrally embedded in a mesodermal PNA-binding matrix that particularly accumulates underneath vesicular constriction sites, as demonstrated for the segregation of the prosencephalon at HH9 and the cerebellar rhombomere R1 from R2 at HH13. The subsequent period of hindbrain differentiation is analyzed by cholinesterase (AChE, BChE) and peanut lectin histochemistry, by the BrdU and the neurite-specific G4 antibodies. Preotically, differentiation of two pairs of rhombomeres (R4 + R5, R2 + R3) starts in R4, immediately followed by R2. The caudal rhombomeres of both pairs are delayed (R5, R3). Then the postotic rhombomere is subdivided, whereby R7 differentiates before R6. Thus, the development in the direct vicinity of the otic vesicle is delayed (R5, R6). R7 is the last rhombomere that is demarcated caudally. Based on these findings, we postulate two processes that may regulate rhombomere formation in the chicken embryo: (a) an early rostrocaudal wave establishing the major brain vesicles, (b) a superimposed pairwise segmentation emanating rostrally and caudally from the otic vesicle. The segregation of the cerebellar rhombomere is a late step.
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PMID:Patterning of chick brain vesicles as revealed by peanut agglutinin and cholinesterases. 169 41

Cholinergic denervation of the hippocampal formation has been extensively studied in rodents but not in primates. Therefore we studied the changes in acetylcholinesterase histochemical staining of the hippocampus occurring after bilateral transection of the fornices in the cynomolgus monkey. Animals were sacrificed 1.5, 6, 13, and 23 weeks after surgery. We found a 40-50% reduction in the density of acetylcholinesterase-positive fibers in the four analyzed regions (dentate gyrus, CA3, CA1, and subiculum) 1.5 week after surgery and a 60-80% reduction at longer time intervals. The characteristic diffuse AChE staining found in hippocampi from control animals disappeared after fornix lesion, except in the inner third of the molecular layer of the dentate gyrus. We did not find any evidence of spontaneous cholinergic reinnervation over the 6-month period. Thus, as in rats, fornix lesion produces dramatic changes in hippocampal AChE staining, presumably caused by a massive cholinergic denervation. However, in contrast to rodents, spontaneous reinnervation does not seem to occur in the months following the lesion in primates.
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PMID:Loss of hippocampal acetylcholinesterase staining after fornix lesion in the monkey. 171 8

QSAR analyses have been performed on the substituted indanone and benzylpiperidine ring substructures of a set of acetylcholinesterase, AChE, inhibitors of which 1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine hydrochloride is a potent in vitro and ex vivo inhibitor. The method of molecular decomposition-recomposition was used to define the sets of molecular substructures and corresponding in vitro inhibition databases. A QSAR involving the magnitude of the dipole moment, the highest occupied molecular orbital (HOMO) energy, and a specific pi-orbital wave function coefficient of the substituted indanone ring substructure was constructed and found to be significant. The absence of any molecular-shape or bulk term in the QSAR, coupled with some of the relatively large substituents used to construct the QSAR, suggests considerable space is available around the indanone ring during the inhibition process. A set of QSARs were constructed and evaluated for substituents on the aromatic ring of the benzylpiperidine substructure. The most significant QSAR involves a representation of molecular shape, the largest principal moment of inertia, and the HOMO of the substituted aromatic ring. It appears that upon binding the receptor "wall" is closely fit around the benzyl ring, especially near the para position. Overall, the QSAR analysis suggests inhibition potency can be better enhanced by substitution on the indanone ring, as compared to the aromatic sites of the benzylpiperidine ring. Moreover, inhibition potency can be rapidly diminished, presumably through steric interactions with the receptor surface of AChE, by substitution of moderate to large groups on the benzyl ring, particularly at the para position.
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PMID:QSAR analyses of the substituted indanone and benzylpiperidine rings of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. 173 51

Cerebrospinal fluid acetylcholinesterase (CSF AChE) was determined for elderly delirious patients during the acute stage and after a 1-year followup, and the AChE levels were compared with those of age-equivalent controls. At the acute phase, the AChE levels of the delirious patients were in the same range as those of the control group, but during the followup, a slight declining trend was observed. These results do not unambiguously support the previously suggested role of cholinergic dysfunction in the pathogenesis of acute delirium, although the augmented striatal release of AChE in hyperkinetic and mixed delirium may mask the involvement of cholinergic neurons.
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PMID:A longitudinal study of cerebrospinal fluid acetylcholinesterase in delirium: changes at the acute stage and at one-year followup. 175 28


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