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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochemical characterization of cholinesterase activity (ChE) was carried out on the Antarctic scallop Adamussium colbecki collected in winter 2000 from Campo Icaro (Ross Sea, Antarctica) in order to increase its suitability as a sentinel organism for monitoring the Antarctic environment. The digestive gland, gills and adductor muscle were investigated for substrate specificity and inhibitors sensitivity using acetylthiocholine iodide (ASCh) and butyrylthiocholine iodide (BSCh) as substrates and tetra (monoisopropyl)pyrophosphor-tetramide (Iso-OMPA), 1,5-bis(4-allyldimethylammoniumphenyl)-penthan-3-one dibromide (BW284c51) and the insecticide chlorpyrifos as inhibitors. Effect of in vivo exposure to ZnCl(2) was also investigated. All the tissues expressed ChE activity (gill > adductor muscle > digestive gland) and low substrates specificity throughout the hydrolysis of both ASCh and BSCh substrates. Partial (25-29%) and total inhibition (100%) of ChE activity in gills was demonstrated following in vitro incubation with Iso-OMPA and BW284c51 (3 mM), respectively. Concentration-dependent inhibition was also evident with chlorpyrifos in the range 10(-4)-10(-10) M (IC(50) 10(-6)) while in vivo exposure to ZnCl(2) did not seem to affect ChE activity in the scallop. The potential use of ChE in the A. colbecki as biomarker for monitoring water contamination in the marine Antarctic environment is discussed.
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PMID:Cholinesterase activities in the Antarctic scallop Adamussium colbecki: tissue expression and effect of ZnCl2 exposure. 1517 60

Cholinesterases (ChE) from brain, muscle and liver in Nile tilapia (Oreochromis niloticus) were characterized using three substrates: acetylthiocholine iodide, propionylthiocholine iodide, and butyrylthiocholine iodide. Eserine was used as a total ChE inhibitor; BW284c51 and iso-OMPA were used as selective inhibitors for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), respectively. The results indicate that AChE is the enzyme present in brain, whereas in both liver and muscle, the presence of atypical ChEs are suggested. These findings indicate that characterization of ChE is necessary prior to use in monitoring programs.
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PMID:Characterization of cholinesterase activity from different tissues of Nile tilapia (Oreochromis niloticus). 1517 74

Resistance of the codling moth Cydia pomonella (L.) to azinphos-methyl is not based on enhanced detoxifying enzymes like oxidation mediated by mixed function oxidases or by glutathione S-transferases. Synergism by S,S,S-tributylphosphoro-trithioate was evident, but the overall activity of general esterases using p-nitrophenyl acetate as the substrate was similar in resistant and susceptible insects. In comparison to acetylcholinesterase (AChE) from susceptible adult codling moth, the enzyme of insects resistant to azinphos-methyl has low affinities (higher K(m) values) to the substrates acetylthiocholine (ATCh) and propionylthiocholine. This difference indicates a possible amino acid alteration at the catalytic or anionic binding sites of the resistant enzyme. Inhibition studies revealed no apparent differences in sensitivity of AChE enzymes from resistant and susceptible moths to organophosphorus compounds (OPs), carbamate insecticides and quaternary ammonium ligands. MEPQ (7-Methylethoxyphosphinyloxy)-1-methylquinolinium) is the most powerful OP inhibitor acting at a nM range, while chlopyrifos oxon, azinphos-methyl oxon and paraoxon are less inhibitory by 22.9, 82.3 and 475 fold, respectively. The codling moth AChE is a typical enzyme that displays substrate inhibition by ATCh, negligible hydrolysis of butyrylthiocholine, very high sensitivity to the bisquaternary ammonium compound BW284c51 and it is not inhibited by the powerful butyrylcholinesterase inhibitor iso-OMPA. Of the three carbamates examined, only carbaryl was inhibitory at the mM range while pirimicarb and aldicarb were inactive. Of the quaternary ammonium ligands (except for the powerful BW284c51), edrophonium and decamethonium displayed appreciable inhibition rates, while d-tubocuraine was practically inactive.
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PMID:Evaluation of mechanisms of azinphos-methyl resistance in the codling moth Cydia pomonella (L.). 1537 68

In this study, the acute toxicity and the in vivo effects of commercial chlorpyrifos, carbofuran and glyphosate formulations on cholinesterase (ChE), glutathione S-transferase (GST) and lactate dehydrogenase (LDH) activities of the mosquitofish (Gambusia yucatana) were investigated. In a first phase of the study, head and muscle ChE were characterized with different substrates (acetylthiocholine iodide, s-butyrylthiocholine iodide and propionylthiocholine iodide) and the selective inhibitors eserine hemisulfate, 1,5-bis(4-allyldimethylammoniumphenyl)-pentan-3-one dibromide (BW284C51), and N,N'-diisopropylphosphorodiamic acid (iso-OMPA). The results obtained suggest that the enzyme present in both head and muscle of G. yucatana is mainly acetylcholinesterase (AChE). Acute toxicity was evaluated by exposing fish to several concentrations of single pesticides and of a mixture of chlorpyrifos/glyphosate. LC50 values were determined after 96 h of exposure, except in the case of carbofuran for which LC50 was calculated after 24 h since almost all the fish died within this period. LC50 values were 0.085 mg/l for chlorpyrifos, 17.79 mg/l for glyphosate, 0.636 mg/l for carbofuran and 0.011 mg/l for the chlorpyrifos/glyphosate mixture. A Toxic Unit approach was used to compare the toxicity of chlorpyrifos and glyphosate when occurring in a mixture with their toxicities as single compounds. Synergistic effects of chlorpyrifos and glyphosate when present in a mixture were found. At the end of each bioassay (24 h for carbofuran, 96 for the other substances/mixture), effects on biomarkers were analyzed. Muscle LDH activity was not altered by any of the three pesticides tested. Gill GST activity was significantly inhibited (40%) by carbofuran after 24 h of exposure to concentrations equal or higher than 0.06 mg/l. ChE muscle and head activity were significantly inhibited (50% and 30%, respectively) by carbofuran at concentrations equal or higher than 0.25 mg/l. Chlorpyrifos induced a significant inhibition of both muscle and head ChE (80% and 50%, respectively) after 96 h of exposure to concentrations equal or higher than 0.05 mg/l. Carbofuran did not induce significant alterations of fish ChE. The ChE EC50 determined for chlorpyrifos/glyphosate mixture (0.070 mg/l) was higher than the correspondent value calculated for chlorpyrifos alone (0.011 mg/l) suggesting an antagonistic effect of glyphosate on ChE inhibition by chlorpyrifos. ChE activity of G. yucatana seems to be a good biomarker to diagnose the exposure of wild populations of this species exposed to anticholinesterase pesticides.
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PMID:In vivo evaluation of three biomarkers in the mosquitofish (Gambusia yucatana) exposed to pesticides. 1562 Jul 56

Isolated intact human pulmonary arteries and veins were used to determine the acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) activities in the absence or presence of two selective cholinesterase (ChE) inhibitors, iso-OMPA or BW284c51, respectively. These results were compared with the mRNA levels for each enzyme in human pulmonary vessels. Total ChE activities measured in presence of acetylthiocholine (ACTI, 1 mM) in intact vascular preparations were 45+/-04 and 114+/-07 mU/g tissue in human pulmonary arteries (n=14) and veins (n=14), respectively. These activities were completely abolished in presence of 10 microM neostigmine. In both types of vessels AChE and BChE activities were observed. These activities were at least 2-fold higher in human pulmonary veins when compared with arteries and were correlated with the accumulation of the corresponding transcripts (n=8). In each type of vessel, similar total ChE activities were detected in homogenized and intact preparations, while in human bronchial preparations this activity was 5-fold higher in homogenates than in intact preparations. Together these results provide evidence that the ChE activities in human pulmonary vessels may be extracellular and that the higher activity measured in veins as compared to arteries was associated with the differential accumulation of the corresponding transcripts.
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PMID:Cholinesterase activity in human pulmonary arteries and veins: correlation with mRNA levels. 1573 36

Activities of glutathione S-transferases (GST) and cholinesterase (ChE) from Paracentrotus lividus were investigated as possible biomarkers of environmental contamination in the coastal zone. In the first phase of the study, the activity of both enzymes was determined in various tissues in order to select the most appropriate ones to be used in the following assays. In the second phase, the ChEs present in ambulacra were characterized using different substrates and selective inhibitors. In the next phase, laboratory bioassays were performed with dilutions of water-accommodated fraction of #4 fuel-oil (WAF) and benzo[a]pyrene (BaP) to determine the response of those enzymes to these pollutants and, finally, the activity of both enzymes was determined during a year in indigenous specimens from six sites on the Northwest coast of Portugal, with different pollution levels, to determine basal values and seasonal variations of ChE and GST activities. Among the several tissues tested, ambulacra and the anterior portion of the intestine were selected for ChE and GST assays, respectively. The determination of ChE in ambulacra tissue may be performed in a non-destructive way. Ambulacra ChE hydrolysed acetylthiocholine preferentially to propionylthiocholine and butyrylthiocholine and, inhibition by excess of substrate was observed. Enzymatic activity was almost fully inhibited by eserine sulfate (>98%) at concentrations equal or higher than 6.25 microM. Sensitivity to both BW284C51 (reaching 98% at 200 microM) and iso-OMPA (73% at 8 mM) was found. In laboratory bioassays, GSTs activity was inhibited by WAF and induced by BaP, whereas ChE activity was not affected by any of these environmental contaminants. Seasonal variations in enzymatic activities were found. For example, in a reference site, ChE values changed from 52.2 +/- 9.3 U mg(-1) protein in autumn to 71.8 +/- 13.3 U mg(-1) protein in spring, while GST activity changed from 129.9 +/- 29.8 U mg(-1) protein in winter to 279.0 +/- 48.0 U mg(-1) protein in autumn. Sea-urchins from reference sites presented significantly higher values of both ChE and GST than animals from contaminated sites in all seasons. In conclusion, the results of this study indicate that (i) ambulacra and the anterior portion of intestine are the most suitable tissues to measure ChE and GST activities, respectively; (ii) only one form of ChE seems to be present in ambulacra, showing properties of both typical acetylcholinesterase (AChE) and pseudocholinesterase (PChE); (iii)P. lividus GST is sensitive to both WAF and BaP even after acute exposures while ChE is not, and (iv) in spite of the significant seasonal variations observed in both enzymes in the field, P. lividus ChE and GST were capable of discriminate sites with different contamination levels and, thus, they are suitable for use as biomarkers in biomonitoring studies in the coastal zone.
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PMID:Sea-urchin (Paracentrotus lividus) glutathione S-transferases and cholinesterase activities as biomarkers of environmental contamination. 1579 94

Mefloquine is effective against drug-resistant Plasmodium falciparum. This property, along with its unique pharmacokinetic profile, makes mefloquine a widely prescribed antimalarial drug. However, mefloquine has neurologic effects which offset its therapeutic advantages. Cellular actions underlying mefloquine's neurologic effects are poorly understood. Here, we demonstrate that mefloquine inhibits human recombinant acetylcholinesterase. To explore the consequences of this action, we investigated mefloquine's actions at a model cholinergic synapse, the mouse neuromuscular junction. Sharp electrode recording was used to record miniature endplate potentials (mepps) in the Triangularis sterni muscle. Within 30 min of exposure to 10 microM mefloquine, mepps were altered in three ways: 10-90% rise time, 90-10% decay time and amplitude significantly increased. Mepp decay time increased linearly with mefloquine concentration. Pretreatment of muscles with the cholinesterase inhibitor physostigmine (3 microM) precluded the mefloquine-induced prolongation of mepp decay. Mefloquine also prolonged mepps at endplates of acetylcholinesterase knock-out mice. Since the selective butyrylcholinesterase inhibitor iso-OMPA (100 microM) also prolonged mepp decay at the neuromuscular junction of acetylcholinesterase knock-out mice, mefloquine inhibition of this enzyme is physiologically relevant. The non-selective anti-cholinesterase action can contribute to the neurologic effects of mefloquine.
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PMID:Mefloquine inhibits cholinesterases at the mouse neuromuscular junction. 1608 Nov 11

Acetylcholinesterase and butyrylcholinesterase activities emerge in association with plaques and tangles in Alzheimer's disease. These pathological cholinesterases, with altered properties, are suggested to participate in formation of plaques. The present experiment assessed the ability of rivastigmine, a clinically utilized agent that inhibits acetylcholinesterase and butyrylcholinesterase activities, to inhibit cholinesterases in plaques and tangles. Cortical sections from cases of Alzheimer's disease were processed using cholinesterase histochemistry in the presence or absence of rivastigmine. Optical densities of stained sections were utilized as a measure of inhibition. The potency of rivastigmine was compared with those of other specific inhibitors. Optimum staining for cholinesterases in neurons and axons was obtained at pH 8.0. Cholinesterases in plaques, tangles and glia were stained best at pH 6.8. Butyrylcholinesterase-positive plaques were more numerous than acetylcholinesterase-positive plaques. Rivastigmine inhibited acetylcholinesterase in all positive structures in a dose-dependent manner (10(-6)-10(-4) M). However, even at the highest concentration, faint activity remained. In contrast, rivastigmine resulted in complete inhibition of butyrylcholinesterase in all structures at 10(-5) M. Rivastigmine was equipotent to the specific acetylcholinesterase inhibitor BW284C51 and more potent than the butyrylcholinesterase inhibitors iso-OMPA and ethopropazine. In conclusion, rivastigmine is a potent inhibitor of acetylcholinesterase and a more potent inhibitor of butyrylcholinesterase in plaques and tangles. Unlike other cholinesterase inhibitors tested, rivastigmine inhibited cholinesterases in normal and pathological structures with the same potency. Thus, at the therapeutic concentrations used, rivastigmine is likely to result in inhibition of pathological cholinesterases, with the potential of interfering with the disease process.
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PMID:Rivastigmine is a potent inhibitor of acetyl- and butyrylcholinesterase in Alzheimer's plaques and tangles. 1621 45

Acute inhibition of synaptic acetylcholinesterase (AChE) is fatal to normal animals, but AChE-knockout mice (AChE-/-) expressing normal levels of butyrylcholinesterase (BChE) could live to adulthood without AChE expression. The present study was undertaken to determine whether compensatory mechanisms occur in the mutant that allow an effective neuromuscular transmission in the chronic absence of AChE. For this we evaluated neuromuscular transmission and the distribution of nicotinic acetylcholine receptors (nAChRs) and motor nerve terminals on isolated nerve-muscle preparations from AChE-/- mice. AChE-/- hemidiaphragm muscles maintained at 32 degrees C can support muscle twitches, and tetanic contractions during intermittent nerve-stimulation over a wide range of physiological frequencies, even though they develop less force, than age-matched wild-type (AChE+/+) muscles. Tetanic fade in AChE-/- muscles was temperature-sensitive and more marked at 22 degrees C than at 32 degrees C. Inhibition of BChE by tetraisopropylpyrophosphoramide (Iso-OMPA) intensified tetanic fade in AChE-/- muscles, but had no effect on AChE+/+ muscles, suggesting that BChE plays a protective role in nerve terminals. Skeletal muscles from AChE-/- mice adapted to the lack of AChE enzymatic activity by triggering a synaptic remodeling that critically occurred between the second and third week of postnatal development, during synapse elimination. In AChE-/- muscles nAChRs distributed in a smaller and fragmented surface area, that mirrored the branching pattern of motor nerve terminals. These findings indicate that the neuromuscular system exhibits a remarkable plasticity and adaptive responses to the chronic absence of AChE activity that has important consequences for the functioning of the neuromuscular junction.
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PMID:Synaptic remodeling at the skeletal neuromuscular junction of acetylcholinesterase knockout mice and its physiological relevance. 1627 83

The present study attempted to pharmacologically characterize the muscarinic receptor subtypes mediating contraction of human umbilical vein (HUV).HUV rings were mounted in organ baths and concentration-response curves were constructed for acetylcholine (ACh) (pEC50: 6.16+/-0.04; maximum response 80.00+/-1.98% of the responses induced by serotonin 10 microM). The absence of endothelium did not modify the contractile responses of ACh in this tissue. The role of cholinesterases was evaluated: neither neostigmine (acetylcholinesterase inhibitor) nor iso-OMPA (butyrylcholinesterase inhibitor) modified ACh responses. When both enzymes were simultaneously inhibited, a significantly but little potentiation was observed (control: pEC50 6.33+/-0.03; double inhibition: pEC50 6.57+/-0.05). Atropine, nonselective muscarinic receptors antagonist, inhibited ACh-induced contraction (pKB 9.67). The muscarinic receptors antagonists pirenzepine (M1), methoctramine (M2) and pFHHSiD (M3) also antagonized responses to ACh. The affinity values estimated for these antagonists against responses evoked by ACh were 7.58, 6.78 and 7.94, respectively. On the other hand, PD 102807 (M4 selective muscarinic receptors antagonist) was ineffective against ACh-induced contraction.In presence of a blocking concentration of pirenzepine, pFHHSiFD produced an additional antagonism activity on ACh-induced responses. The M1 muscarinic receptors agonist McN-A-343 produced similar maximum but less potent responses than ACh in HUV. The calculated pA2 for pirenzepine against McN-A-343 induced responses was 8.54. In conclusion, the data obtained in this study demonstrate the role of M1 muscarinic receptor subtypes and suggest the involvement of M3 muscarinic receptor subtypes in ACh-induced vasoconstriction in HUV rings. In addition, the vasomotor activity evoked by ACh does not seem to be modulated by endothelial factors, and their enzymatic degradation appears to have little functional relevance in this tissue.
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PMID:Pharmacological characterization of muscarinic receptor subtypes mediating vasoconstriction of human umbilical vein. 1644 91


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