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)

1. The effects of carbamylcholine (CaCh) (acetylcholine agonist) and pyridostigmine (Pyr) (acetylcholinesterase inhibitor), on the activity of cytoskeleton-bound and cytosolic phosphofructokinase (PFK), the rate-limiting enzyme in glycolysis, and ATP levels, were studied in rat tibialis anterior (TA) muscle, heart, and brain. 2. In the TA muscle, a marked (about three-fold) increase in the allosteric activity of cytosolic (soluble) PFK was found, 3-5 min following the injection of CaCh or Pyr. The intracellular distribution of the enzyme was not affected by both drugs. Stimulation of glycolysis in this muscle was also expressed by a significant increase in the concentrations of glycolytic intermediates and lactate. Glucose 1,6-bisphosphate (Glc-1,6-P2) levels were unchanged, whereas fructose-2,6-bisphosphate (Fru-2,6-P2) was increased. Glycogenolysis was also stimulated, as deduced from the decrease in glycogen content. The stimulation of glycolysis, induced by both drugs, was accompanied by an increase in ATP level in the TA muscle. 3. In contrast to the stimulatory action of CaCh or Pyr on glycolysis in the TA muscle, both drugs had no effect on cytosolic and cytoskeletal PFK in heart and brain. However, ATP content in both heart and brain was markedly reduced by these drugs, most probably due to their reported harmful effects on mitochondrial function, leading to tissue damage. 4. Electron microscopic studies of TA muscle and heart from rats treated with CaCh or Pyr, revealed severe damage of heart but no harmful effects on TA muscle, which is a muscle with high glycolytic and low oxidative capacity. The present experiments suggest that the accelerated glycolysis in this muscle induced by both drugs, supplies ATP, thus preventing muscle damage.
Gen Pharmacol 1996 Oct
PMID:Effects of carbamylcholine and pyridostigmine on cytoskeleton-bound and cytosolic phosphofructokinase and ATP levels in different rat tissues. 898 Oct 75

1. A differential inhibition assay was developed for the quantitative determination of cholinesterase isoenzymes acetylcholinesterase (AChE; EC 3.1.1.7), cholinesterase (BChE; EC 3.1.1.8), and atypical cholinesterase in small samples of left ventricular porcine heart muscle. 2. The assay is based on kinetic analysis of irreversible cholinesterase inhibition by the organophosphorus compound N,N'-di-isopropylphosphorodiamidic fluoride (mipafox). With acetylthiocholine (ASCh) as substrate (1.25 mM), hydrolytic activities (A) of cholinesterase isoenzymes were determined after preincubation (60 min, 25 degrees C) of heart muscle samples with either saline (total activity, A tau), 7 microM mipafox (AM1), or 0.8 mM mipafox (AM2): (BChE) = A tau-AM1, (AChE) = AM1-AM2, (Atypical ChE) = AM2. 3. The mipafox differential inhibition assay was used to determine the substrate hydrolysis patterns of myocardial cholinesterases with ASCh, acetyl-beta-methylthiocholine (A beta MSCh), propionylthiocholine (PSCh), and butyrylthiocholine (BSCh). The substrate specificities of myocardial AChE and BChE resemble those of erythrocyte AChE and serum BChE, respectively. Michaelis constants KM with ASCh were determined to be 0.15 mM for AChE and 1.4 mM for BChE. 4. Atypical cholinesterase, in respect to both substrate specificity and inhibition kinetics, differs from cholinesterase activities of vertebrate tissue and, up to now, could be identified exclusively in heart muscle. The enzyme's Michaelis constant with ASCh was determined to be 4.0 mM. 5. The reversible inhibitory effects of physostigmine (eserine) and quinidine on heart muscle cholinesterases were investigated using the differential inhibition assay. With all three isoenzymes, the inhibition kinetics of both substances were strictly competitive. The physostigmine inhibition of AChE was most pronounced (Ki = 0.22 microM). Quinidine most potently inhibited myocardial BChE (Ki = 35 microM).
Gen Pharmacol 1997 Apr
PMID:Mipafox differential inhibition assay for heart muscle cholinesterases: substrate specificity and inhibition of three isoenzymes by physostigmine and quinidine. 914 26

1. 9-Amino-1,2,3,4-tetrahydroacridine (THA), an acetylcholinesterase inhibitor, significantly inhibited in vitro the ATP diphosphohydrolase activity of synaptosomes from the cerebral cortex and hippocampus of adult rats. 2. THA did not inhibit in vitro the 5'-nucleotidase activity of synaptosomes from cerebral cortex and hippocampus of rats. 3. THA exerted an uncompetitive inhibition on ATP diphosphohydrolase activity. This mechanism of inhibition was the same in the 2 different synaptosomal fractions (cerebral cortex and hippocampus) studied. 4. THA, proposed as a drug for the treatment of Alzheimer's disease, can alter in vitro ATP degradation in synaptosomes from the central nervous system.
Gen Pharmacol 1997 May
PMID:Effects of 9-amino-1,2,3,4-tetrahydroacridine (THA) on ATP diphosphohydrolase (EC 3.6.1.5) and 5'-nucleotidase (EC 3.1.3.5) from rat brain synaptosomes. 918 16

1. The cholinesterases play an important role in the innervation of organs. The ratio of solubilized to membrane-bound cholinesterase and the quantitative distributions of acetylcholinesterase and butyrylcholinesterase were measured in different segments of the gut of carp (Cyprinus carpio) connected with different types of nerve-muscle synapses in different parts of the alimentary tract. 2. The inhibition of acetylcholinesterase (EC 3.1.1.7.) by the herbicide paraquat and the insecticide metidathion was measured in different parts of the gut of carp. 3. Metidathion and paraquat significantly decreased the activity of acetylcholinesterase in different segments of the alimentary tract of common carp, in a concentration-dependent manner.
Gen Pharmacol 1997 Jul
PMID:Quantitative distributions of different cholinesterases and inhibition of acetylcholinesterase by metidathion and paraquat in alimentary canal of common carp. 919 93

It has been proposed that amplification of genes for esterase that provide resistance to insecticides may originate from transposition events. To test this hypothesis, we have constructed a minigene coding for a soluble acetylcholinesterase under the control of a nontissue-specific promoter (hsp70). When introduced into Drosophila, the gene is expressed in all tissues and the extra acetylcholinesterase produced confers a low level of insecticide resistance (twofold). The minigene was mobilized by crossing the initial transformant with a strain providing a source of P-element transposase. After 34 generations of exposure to the organophosphate parathion, we obtained a strain with a higher resistance (fivefold). This strain had only one extra Ace gene, which overexpressed acetylcholinesterase. Thus, following transposition, resistance resulted from the overexpression of a single copy of the gene and not from gene amplification.
Mol Gen Genet 1997 Oct
PMID:Transposition-mediated transcriptional overexpression as a mechanism of insecticide resistance. 939 32

1. The effects of two model inducers of the cytochrome P450 system, phenobarbital (PB) and beta-naphthoflavone (NF), on the toxicity of paraoxon were studied in rats. 2. Paraoxon toxicity was measured by inhibition of brain acetylcholinesterase (AChE) activity. 3. PB treatment did not affect the toxicity of paraoxon, whereas NF increased the inhibition of brain AChE. PB administration slightly increased the activities of some peripheral cholinesterases and carboxylesterases, as well as liver microsomal paraoxonase (Pxase). 4. NF administration, in contrast, decreased the activities of peripheral esterases. Serum Pxase activity was reduced by both inducers. 5. Hepatic CYP2B and CYP1A were markedly induced by PB and NF, respectively. 6. Cytochrome P450 isoenzymes induced by PB or NF seemed not to be critical in the detoxification of paraoxon in vivo. NF caused a general reduction of peripheral esterases, which led to an increase in paraoxon toxicity. 7. The results indicated the great importance of peripheral cholinesterases and carboxylesterases as a detoxifying mechanism of paraoxon. The role of serum paraoxonase was not critical.
Gen Pharmacol 1998 Aug
PMID:Effect of phenobarbital and beta-naphthoflavone on activities of different rat esterases after paraoxon exposure. 968 78

1. The effect of several central nervous system active drugs was studied in vitro on ATPase-ADPase activity and acetylcholinesterase (AChE) activity from the cerebral cortex of adult rats. 2. Lithium (1.0-10.0 mM) had no effect on either ATPase-ADPase or acetylcholinesterase activity. 3. Imipramine (0.5-5.0 mM), desipramine (0.5-5.0 mM), amitriptyline (0.1-1.0 mM) and diazepam (0.5-2.0 mM) inhibited ATP and ADP hydrolysis at all concentrations tested. 4. AChE activity was altered by imipramine (1.0-2.0 mM) and by diazepam (0.5-2.0 mM). 5. The possible participation of ATP diphosphohydrolase and AChE in the action of these drugs cannot be ruled out. The probable reduction of ATP, ADP and acetylcholine hydrolysis by the inhibitory effect of these drugs is discussed.
Gen Pharmacol 1998 Oct
PMID:In vitro effect of central nervous system active drugs on the ATPase-ADPase activity and acetylcholinesterase activity from cerebral cortex of adult rats. 979 15

The effect of transient cerebral ischemia on acetylcholinesterase (AChE) synthesis was studied in rats by a modified pharmacohistochemical method. The procedure involved in vivo irreversible inhibition of AChE by administration of the inhibitor diisopropyl fluorophosphate (DFP; 1.2 mg/kg b.w., i.m.) 1 h before 30 min forebrain ischemia (the four-vessel occlusion model). At the onset of ischemia, 70-75% of AChE was inhibited in the brain. Recirculation was followed by histochemical and biochemical investigations of newly synthesized AChE in the striatum, septum, cortex and hippocampus. Control sham-operated animals were treated with the same dose of DFP. For correlation, rats not treated with DFP were subjected to the same ischemic procedures and investigated simultaneously. In these rats, significant decrease in AChE activity was found in the striatum, septum and hippocampus during 24 h recirculation. In DFP treated rats, ischemia markedly depressed resynthesis of AChE; after 4 h recirculation, AChE activity was decreased by 45-60% in all investigated areas in comparison with controls and the AChE histochemistry showed only slightly stained neurons in the striatum and septum. Twenty-four hours after ischemia, these neurons were densely stained and the increase in AChE activity indicated a partial recovery of the enzyme synthesis. These results suggest that the depression of AChE synthesis after forebrain ischemia is probably transient, not accompanied by cholinergic neuron degeneration.
Gen Physiol Biophys 1999 Mar
PMID:Depression of acetylcholinesterase synthesis following transient cerebral ischemia in rat: pharmacohistochemical and biochemical investigation. 1037 21

Changes in cholinesterases activities in daunorubicin cardiomyopathy and in dexrazoxane (DRZX)-treated daunorubicin cardiomyopathy were investigated in rabbits. Acetyl- and butyrylcholinesterase (AChE and BuChE) were determined using Ellman's method. In the serum, a significant decrease of BuChE was observed in the daunorubicin group (9.05 at the beginning and 7.15 microcat/l at the end of the experiment). After DRZX, no significant changes were found and a significant increase in BuChE was observed in the control group (10.26-12.38 microcat/l). AChE activity in the left and right cardiac ventricles was not significantly different between the groups while in the septum there was a significantly lower AChE activity found in the daunorubicin group only. BuChE activity was significantly decreased in the left (15.64 ncat/g) and right (19.27 ncat/g) heart ventricles, in the septum and in the liver in the daunorubicin group. A significant decrease in serum total protein and albumin was demonstrated only in the daunorubicin group. Our results support the hypothesis about the influence of daunorubicin on protein (and enzyme) synthesis in the liver and heart. A protective effect of DRZX on cholinesterases activity was observed. The changes in cholinesterase activities may thus reflect their possible role in cardiomyopathy.
Gen Physiol Biophys 1999 Dec
PMID:Cholinesterases in dexrazoxane-treated daunorubicin cardiomyopathy in rabbits. 1076 32

An enzyme-linked immunosorbent assay (ELISA) has been developed for a conjugated bile acid, 7alpha,12alpha,24-trihydroxy-5alpha-cholan-3-one 24-sulfate (commonly referred to as 3-keto petromyzonol sulfate [3kPZS]), a pheromone released by reproductively mature male sea lampreys to attract sexually mature females. A polyclonal antiserum against the pheromone was raised by injecting 3-keto petromyzonol 24-hemisuccinate (3kPZ-HS) conjugated to bovine serum albumin into rabbits. The enzyme label was prepared by conjugating 3kPZ-HS to acetylcholinesterase. The standard curve had a working range of 20 pg-10 ng/well. Intra- and inter-assay variations were less than 5 and 12%, respectively. The antiserum had 100% cross-reaction with 3-keto petromyzonol and 3-keto allocholic acid but less than 0.2% cross-reaction with petromyzonol, allocholic acid, cholic acid, and taurolithocholic acid sulfate. The assay was applied to water which had been conditioned for 4h by either larvae, parasitic juveniles, ovulating females, pre-spermiating males, or spermiating males. Immunoactive material (average 200 ng/ml, which is equivalent to 500 microg animal/h) was only found in water from the reproductively mature males and diluted parallel with the standard curve. Assay of water samples collected from male lampreys in bisected aquaria also established that 99.6% of the immunoactive material emanated from the front end of the fish. This assay has applications in both physiological and ecological aspects of sea lamprey reproduction.
Gen Comp Endocrinol 2002 Dec
PMID:Development and application of an ELISA for a sex pheromone released by the male sea lamprey (Petromyzon marinus L.). 1246 Jun


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