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 action of 1-pyrene-butyrylcholine, a new cholinergic fluorescent probe, has been studied at the cellular level using electrophysiological and fluorescence techniques. The spectroscopic properties of the probe were found to be similar to those pf pyrene-butyric acid, the excited-state lifetime in air-saturated aqueous solutions being 92 nsec. At micromolar concentrations the probe was found to exert a nondepolarizing, reversible blocking action at the neuromuscular junction of the frog. The same cholinolytic effect was observed in hypersensitive denervated muscles. The synaptic localization of the probe could be observed with fluorescence microscopy using sub- and micromolar concentrations. Treatment of the nerve-muscle preparations with proteolytic enzymes, resulting in the separation of the nerve ending from the muscle end-plate, enabled a distinction to be made between the fluorescence arising from these two parts of the synapse. Intense presynaptic fluorescence was observed, and was not altered by micromolar concentrations of alpha-bungarotoxin, d-tubocurarine, hemicholinium, or cholinesterase inhibitors. Faint reversible staining of the end-plate region was observed in enzymically treated muscles and was inhibited by prior treatment with alpha-bungarotoxin. Fluorescent alpha-toxin revealed similar patterns of fluorescence in the end-plate of enzyme-treated muscles. The postsynaptic localization of the fluorescent probe is therefore tentatively identified as the one producing the cholinolytic effect upon binding to acetylcholine receptor sites.
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PMID:1-Pyrene-butyrylcholine: a fluorescent probe for the cholinergic system. 108 Dec 27

The effects of toluene and n-hexane on rat synaptosomal membrane fluidity and the integral enzymes acetylcholinesterase (AChE) and ATPase were studied in vitro. The synaptosome membranes were isolated in Percoll and sucrose gradients. After adding toluene and n-hexane to the incubation mixture (37 degrees) in 2,4,6 and 8 mM concentrations, the fluidity changes were measured by the lateral pyrene diffusion method from Percoll-isolated membranes, and the ATPase and acetylcholinesterase activities were determined from both synaptosome isolations. Addition of toluene caused a linearly correlated increase of the synaptosomal membrane fluidity and a linear decrease of the AChE activity. The ATPase activity did not decrease linearly but dose-dependently. In contrast to the effects of toluene in vitro, addition of n-hexane in the same concentration range had no comparable influence on membrane fluidity nor on the activities of both integral enzymes despite its even higher lipid/water partition coefficient. Toluene increases synaptosomal membrane fluidity and at the same time inhibits the integral enzymes, probably by disturbing the lipid/protein interaction.
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PMID:Effects of toluene and n-hexane on rat synaptosomal membrane fluidity and integral enzyme activities. 144 47

The ratio of weakly and strongly immobilized populations of membrane-bound maleimide spin label, the excimer to monomer fluorescence ratio of membrane-embedded pyrene, and acetylcholinesterase activity, were evaluated in bovine erythrocyte membrane preparations incubated at 37 degrees C. Oscillations were evident in the values obtained, and the periods of these oscillations were in the range of 1.3 to 1.6 h.
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PMID:Oscillations in erythrocyte membrane preparations. 369 Nov 77

Biochemical, histopathological, and hematological parameters were studied in male Wistar rats after repeated subcutaneous administration of commercial kerosene (0.5 ml/kg body wt, 6 days a week) for a period of 35 days. At necropsy, treatment-related increases in the weights of liver, spleen, and peripheral lymph nodes were noted. Correspondingly, there was an increase in DNA, RNA, protein, and lipid contents of liver and spleen. Histopathological examination of liver, spleen, thymus, kidney, adrenal, and lymph nodes revealed treatment-related lesions. Similarly, biochemical indices studied in liver revealed an increase in alkaline phosphatase and a decrease in benzo[a]pyrene hydroxylase levels. Furthermore serum cholinesterase, carboxylesterase, and albumin levels were significantly diminished while serum alkaline phosphatase levels were found to be greatly enhanced. The findings might be related as the likely systemic effects in workers upon percutaneous kerosene exposure during work.
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PMID:Subcutaneous kerosene toxicity in albino rats. 651 Apr

Aging of acetylcholinesterase (AChE) inhibited by certain organophosphates such as diisopropylfluorophosphate apparently involves dealkylation of the bound organophosphoryl moiety; this renders the inactive enzyme resistant to reactivation by quaternary oximes such as 2-pyridinealdoxime methiodide (2-PAM) which are used in therapy of organophosphate intoxication. The fluorescent pyrenyl organophosphates synthesized in this study were designed to detect putative conformational changes which might explain this resistance. The following inhibitors: 1-pyrenebutyl phosphorodichloride (PBPDC), 1-pyrenebutyl ethylphosphorochloridate (PBEPC), and 1-pyrenebutyl ethylphosphorofluoridate (PBEPF), react specifically with purified electric eel AChE (ki = 10(6)-10(7) M-1 min-1). AChE inhibited by PBEPC and PBEPF was readily reactivated by 2-PAM, while enzyme inhibited PBPDC could not be reactivated. Conjugates were prepared of both PBEPC and PBPDC with AChE, each containing one molecule of florophore per catalytic subunit. Thus two stoichiometric conjugates, PBEP-AChE (non-aged) and POBP-AChE (aged), were obtained. The two complexes exhibited identical absorption spectra, but differed in their steady-state fluorescence spectra. Although the wave-lenths of the excitation and emission spectra were similar, the pyrene fluorescence of the non-aged conjugate was ca. 50% quenched relative to the aged conjugate. Nanosecond fluorescence decay studies revealed two principal lifetime components of pyrene fluorescence. Both were longer for the aged (PBP-AChE) than for the non-aged (PBEP-AChE) conjugate and revealed a ca. 50% lower quantum yield for the non-aged as compared to the aged conjugate. A possible interpretation for these results is that in the aged conjugate the organophosphoryl moiety is less acessible to the external medium. Measurement of quenching of pyrene fluorescence in the aged and non-aged conjugates by the peripheral anionic site ligand propidium also indicated marked conformational differences between the two conjugates, and circular polarization of luminescence measurements revealed that propidium itself induced a substantial conformational change in both conjugates. Fluorescence lifetime measurements revealed that whereas propidium had little effect on the decay parameters for the non-aged conjugate it caused a decrease in lifetime and in relative quantum yield for the aged conjugate. PBEPF virtually eliminated cholinesterase activity in dissociated cord and brain cultures. Fluorescence microscopy reveals fine green fluorescent grains distinctly located throughout many neurons and glia. Labelling is much more pronounced in larger and older neurons. No specific fluorescence could be detected in cultures preincubated with nonfluorescent organophosphates.
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PMID:Fluorescent organophosphates: novel probes for studying aging-induced conformational changes in inhibited acetylcholinesterase and for localization of cholinesterase in nervous tissue. 701 17

Toxicities of pesticidal mixtures in biological systems have not been explored adequately. Therefore, mixtures of ten widely used pesticides were evaluated for their toxicity in ICR male mice (21-24 g). Mice were given four mixtures of alachlor, aldrin, atrazine, 2,4-dichlorophenoxyacetic acid, DDT, dieldrin, endosulfan, lindane, parathion and toxaphene, at 0.01, 0.1, 1.0 and 10 ppm of each of these pesticides, in drinking water for 90 days ad libitum. Also, two mixtures at 2.5 and 5 mg kg-1 of each pesticide in 7.5% Tween-80 in water were administered to additional groups of mice by oral intubation daily for up to 14 days. In relation to the control, the 90-day exposure caused a dose-dependent increase in the liver/body weight ratio (3-44%), a decrease in the pentobarbital (60 mg kg-1, i.p.)-induced sleep time (11-79%) and an increase in the metabolism of aniline (233-399%), amidopyrine (79-231%), phenacetin (127-318%) and benzo[a]pyrene (286-1633%) in the 9000 g hepatic supernatants from the mixture-treated mice. Proliferation, dilatation and fragmentation of the endoplasmic reticulum and scattering of ribosomes were noticed with mixture livers. In the 5 mg kg-1 group, 90% of the animals died by Day 8; incidence of death was considerably less in the 2.5 mg kg-1 group. The serum cholinesterase activity was inhibited by ca. 50% in the 2.5 and 5 mg kg-1 groups on either one or both of Days 8 and 15; the liver/body weight ratio increased by 24-79% and the pentobarbital-induced sleep time decreased by 80-96%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicological evaluation of mixtures of ten widely used pesticides. 832 87

The changes in the structure and properties of erythrocyte membranes that are induced by free fatty acids and their derivatives have been studied. The state of the membrane has been evaluated using the activity of membrane-bound acetylcholinesterase (AChE), the pyrene monomer/excimer fluorescence intensity ratio as an indicator of membrane lipid microviscosity and the fluorescence of membrane-bound 1-anilinonaphtalene-8-sulphonic acid (ANS). Free fatty acids and corresponding aliphatic aldehydes induced an inhibition of membrane-bound AChE, effectively decreased the bulk lipid and protein-bound lipid microviscosity, and quenched the fluorescence of membrane-bound ANS. The type and efficiency of the enzyme inhibition, as well as the efficiency of microviscosity decrease and ANS fluorescence quenching, depended on the hydrophobicity and the end group in the effector molecule. Therefore, it is proposed that fatty acids and related compounds perturb the lipid bilayer and disturb the protein-lipid complementarity of the human erythrocyte membrane.
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PMID:Effect of free fatty acids on the structure and properties of erythrocyte membrane. 854 97

Polycyclic aromatic hydrocarbons (PAHs) are formed during the incomplete combustion of fossil fuels, wood and municipal waste incineration, from internal combustion engines, and from various food cooking operations and are common environmental contaminants which have been detected in surface waters, sediments, soils, plants, and both rural and urban air. In this study, we have shown that, for the first time, in vitro addition of PAHs dose-dependently inhibited the activity of acetylcholinesterase purified from electric eel in a competitive manner. The PAHs containing 3 or higher aromatic rings showed the highest inhibitory effect with the IC50 values between 2 and 6 ppm. Among the PAHs tested, chrysene and pyrene exhibit the highest and lowest potency with IC50 values of 2. 40+/-0.04 and 5.22+/-0.38 ppm, respectively. PAHs with lower number of aromatic rings, such as naphthalene, acenaphthylene and fluorene, and oxygenated PAHs, such as anthraquinone and xanthone, showed no or slight inhibition of the acetylcholinesterase activity.
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PMID:Polycyclic aromatic hydrocarbons inhibit the activity of acetylcholinesterase purified from electric eel. 929 14

This study tested the hypothesis that the inhibition of acetylcholinesterase is greater when the insecticide chlorpyrifos (CPF) is in the presence of several polycyclic aromatic hydrocarbons (PAHs) found in house dust. CPF-oxon (CPFO) inhibition curves of purified AChE (electric eel) were generated in the presence or absence of different concentrations of the PAHs pyrene, benzo(a)pyrene, anthracene, and fluoranthene. Without CPF-oxon, all four PAHs themselves inhibited AChE activity with IC50 values in the range 8.2-17 microM. The IC50 for benzo(a)pyrene with human recombinant AChE was 1.5 microM. When AChE was incubated with CPF-oxon together with the PAHs, the inhibitory effect on AChE was additive. This was exemplified by large (60-80%) and significant (P<0.01) inhibition in AChE activity by the PAHs when combined with nanomolar concentrations of CPF-oxon. Kinetic studies indicated that benzo(a)pyrene inhibited AChE in a noncompetitive manner, and the reduction in maximal velocity (Vmax) by benzo(a)pyrene and CPFO together was the sum of the inhibitory effect of the two inhibitors alone, further supporting an additive effect. These data suggest that some PAHs have anticholinesterase activity, and contribute in an additive manner to the inhibitory effect of CPFO on AChE in vitro. Further research is needed to determine the toxicological relevance of these findings.
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PMID:Additive inhibitory action of chlorpyrifos and polycyclic aromatic hydrocarbons on acetylcholinesterase activity in vitro. 1035 43

Some six or so physiological systems, essential to normal mammalian life, are involved in poisoning; an intoxication that causes severe injury to any one of them could be life threatening. Reversible chemical reactions showing Scatchard-type binding are exemplified by CO, CN- and cyclodiene neurotoxin insecticide intoxications, and by antigen-antibody complex formation. Haemoglobin (Hb) molecular biology accounts for the allosteric co-operativity and other characteristics of CO poisoning, CN- acts as a powerful cytochrome oxidase inhibitor, and antigen binding in a deep antibody cleft between two domains equipped with epitopes for antigen-binding groups explains hapten-specific immune reactions. Covalent chemical reactions with second-order (SN2) kinetics characterize Hg and Cd poisonings, the reactions of organophosphates and phosphonates with acetylcholinesterase and neurotoxic esterase and the reaction sequence whereby Paraquat accepts electrons and generates superoxide under aerobic conditions. Indirect carcinogens require cytochrome P450 activation to form DNA adducts in target-organ DNA and cause cancer, but a battery of detoxifying enzymes clustered with the P450 system must be overcome. Thus, S-metabolism competes ineffectively with target DNA for reactive vinyl chloride (VC) metabolites, epoxide hydrolase is important to the metabolism and carcinogenicity of alfatoxins and polycyclic aromatic hydrocarbons (benzo[a]pyrene, etc.), and the non-toxic 2-naphthylhydroxylamine N-glucuronide acts as a transport form in 2-naphthylamine bladder cancer. VC liver-cancer pathogenesis is explicable in terms of the presence of the glutathione S-transferase detoxifying system in hepatocytes and its absence from the fibroblastic elements, and of the VC concentrations reaching the liver by different administrative routes. In VC carcinogenicity, chemical reactions give imidazo-cyclization products with nucleoside residues of target DNA, and in benzene leukaemia, Z,Z-muconaldehyde forms cyclic products containing a pyrrole residue linked to purine. Increased HbCO concentrations reduce the O2-carrying capacity of the blood, and the changed shape of the O2-Hb dissociation curve parallels disturbance in O2 unloading. CN- acts on electron transport and paralyses respiration. In telodrin poisoning, preconvulsive glutamine formation abstracts tricarboxylic acid intermediates incommensurately with normal cerebral respiration. Antigen-antibody complexing depletes the antibody titre, available against infection. At high doses of Cd, Cd-thionein filtered through the kidneys is reabsorbed and tubular lesions produced. Some organophosphate insecticides promote irreversible acetylcholinesterase phosphorylation and blockade nerve function, and others react with neurotoxic esterase to cause delayed neuropathy. The evidence for Paraquat pulmonary poisoning suggests a radical mechanism involving three interrelated cyclic reaction stages. The action of N- and O8 (O substituent in 6-position of the purine) demethylases explains deletion mechanisms for DNA-alkyl adducts. DNA-directed synthesis in the presence of ultimate carcinogens provides for an estimation of misincorporations, which implicate the same transversions as those found by direct mutagenicity testing. Chemical carcinogens recognize tissue-sensitive cells and modify their heritable genetic complement. Oncoproteins encoded by activated oncogenes signal the transformation of normal cells into cancer cells. The importance of the H-ras oncogene and p53 tumour-suppressor gene is stressed. Antidotal action is analysed; for example, parenteral glutamine administration to telodrin-intoxicated rats restores the depleted cerebral glutamate level and prevents seizures. Glutamate acts as anticonvulsant in petit mal epilepsy. In general, therefore, the reaction of the toxicant-related substance with the relevant target-tissue macromolecule accounts for the biochemical/biological events at a cellular level a
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PMID:Toxic action/toxicity. 1074 Aug 94


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