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)

Motor, sensory and thermoregulatory functions were examined in aging rats (12 months) following two schedules of repeated po administration of the carbamate insecticide carbaryl and these effects were assessed in terms of blood cholinesterase activity. Administration of carbaryl (50 mg/kg) by gavage daily for 30 days resulted in a reduction of locomotor activity in the open-field and in an inhibition of cholinesterase activity within 30 min after the last treatment. Twenty-four h later, only the locomotor effect was evident. After 90 days of exposure to carbaryl in drinking water, no significant effects were observed. These findings suggest that repeated administration of carbaryl to aging rats can induce an impairment of motor function and a reduction of cholinesterase activity, while tolerance develops in some other parameters.
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PMID:Behavioral and biochemical changes following repeated administration of carbaryl to aging rats. 212 84

The effects of benzodiazepines on learning and memory were investigated, using passive avoidance and latent learning tasks, with particular attention being paid to the possible involvement of benzodiazepine receptors and the cholinergic neuronal system. Benzodiazepines such as diazepam, nitrazepam and chlordiazepoxide (CDP) impaired the passive avoidance response when administered before training, but not when administered immediately after training or before the retention test. CDP also impaired latent learning in the water finding task. State-dependent learning was not observed with CDP at the dose used. A benzodiazepine inverse agonist, Ro 15-4513, and a benzodiazepine antagonist, Ro 15-1788, completely and partially reversed, respectively, the disruptive effects of CDP on learning and memory at the doses which did not enhance learning and memory. The disruptive effects of CDP on learning and memory were partially antagonized by a choline esterase inhibitor, physostigmine, and by a blocker for muscarinic acetylcholine receptors, scopolamine, at the doses which increase acetylcholine release. These results suggest that benzodiazepines induce disruptive effects on learning and memory through benzodiazepine receptors, and that benzodiazepine-induced impairment of learning and memory is, at least in part, the result of the dysfunction of the cholinergic neuronal system.
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PMID:Effects of benzodiazepines on passive avoidance response and latent learning in mice: relationship to benzodiazepine receptors and the cholinergic neuronal system. 217 58

A three-month oral subacute toxicity study of mofezolac (N-22), a non-steroidal anti-inflammatory agent, was performed using dose levels of 6, 20, 60 and 200 mg/kg in rats, and recovery was also assessed one month after withdrawal. 1. Toxic signs caused by N-22 administration, observed only in the 200 mg/kg group, were as follows: soiling around the mouth and/or nose, piloerection, anemia, diarrhea, emaciation and decreased spontaneous locomotor activity. Nine males and thirteen females in the 200 mg/kg group excreted bloody diarrhea and died of general exhaustion between weeks four and thirteen of study. 2. In the 200 mg/kg group, decrease in food consumption and suppression of body weight gain were noted in males from about week four and in females from about week six after initiation of administration, and increase in water consumption was noted in males from about week seven. 3. Urinary examination revealed a decline in urinary pH in males of the 20 mg/kg and above groups and elevation of urobilinogen levels in males of the 60 and 200 mg/kg groups. 4. Hematological examination showed decreases in erythrocyte count (RBC), hematocrit value (Ht) and hemoglobin concentration (Hb) and increase in reticulocyte rate in both sexes of the 200 mg/kg group and an increase in neutrophil rate in males of the 200 mg/kg group. 5. Biochemical examination demonstrated a decrease in chloride (Cl-) in males receiving the 20 mg/kg or above doses and a decrease in calcium (Ca++) in males of the 60 and 200 mg/kg groups. Moreover, there were decreases in cholinesterase (ChE) activity, total protein (TP) and albumin (Alb) values, as well as increases in blood urea nitrogen (BUN), uric acid (UA) and potassium (K+) in both sexes of the 200 mg/kg group, along with elevations in GOT and lactate dehydrogenase (LDH) activities in females of the 200 mg/kg group. 6. The absolute and/or relative organ weights for liver, kidneys, spleen and adrenals were increased in the 200 mg/kg group. 7. On pathological examination, perforating ulceration in the jejunum and ileum, turbid ascites, adhesion and inflammatory changes in capsules of the abdominal organs, splenomegaly, mesenteric lymph node hyperplasia and inflammatory changes in the thoracic cavity were observed in dead animals of the 200 mg/kg group. Similar pathological changes were observed in a few survival cases of the 200 mg/kg group. 8. After a one month recovery period, the above-mentioned changes had mostly recovered, indicating that they were reversible.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Three-month oral subacute toxicity study of mofezolac (N-22) in rats]. 223 86

Acephate is a water-soluble organophosphate insecticide whose action on insects has been related to its conversion to methamidophos, a very potent anticholinesterase agent which has caused delayed neuropathy in man. Inhalation and skin exposure to acephate was evaluated in four workers engaged in 8-day campaigns with the formulation of the 97%-pure technical product. Before, during, and after exposure, the workers were monitored for the urine content of acephate and methamidophos, and for erythrocyte (AChE) and plasma (PChE) cholinesterase levels. Median air concentrations (8-hr TWA) ranged from 0.278 to 2.170 mg/m3; median total-body skin deposition ranged from 26.1 to 41.9 mg/day. Based on these values, daily workers' absorption of acephate was estimated to be in the order of 10-20 mg. Urinary excretion of unchanged acephate followed a pattern consistent with exposure, showing peak values of excretion during the workshift or in the eight hr after the end of the workshift. The urine levels of unchanged acephate were found to vary from 1 to 10 mg/L. Methamidophos was not detected in any urine sample (detection limit: 30 micrograms/L). High correlation (r = 0.78) was found between skin exposure level and urine acephate elimination. No changes in AChE or PChE were observed for the workers whose urinary concentrations of acephate were 1 or 2 mg/L. One subject who had urinary acephate excretion between 3 and 8 mg/L, showed slightly decreased values of PChE during exposure and of AChE after exposure.
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PMID:Biological monitoring of human exposure to acephate. 224 Dec 37

The ligand binding and kinetic behaviour of butyrylcholinesterase (EC 3.1.1.8, acylcholine acylhydrolase) from human plasma was studied at 35 degrees C under high hydrostatic pressure. The binding of phenyltrimethylammonium was studied by affinity electrophoresis at various pressures ranging from 10(-3) to 2 kbar. The kinetics of enzyme carbamylation with N-methyl(7-dimethylcarbamoxy)quinolinium iodide was studied in single-turnover conditions up to 1.2 kbar using a high-pressure stopped-flow fluorimeter. Experiments were carried out in different media: 1 mM Tris-HCl (pH 8) with water, water containing 0.1 M lithium chloride and deuterium oxide as solvents. The volume changes (delta V and delta V++) associated with each process were determined from the pressure-dependence of the binding and kinetic constants. Kinetic data show that the binding of substrate to the enzyme leads to a pressure-sensitive enzyme conformational state which cannot accomplish the catalytic act. The pressure-induced inhibitory effect is highly cooperative; it depends on both the nature (charged or neutral) and the concentration of the substrate. Also, large solvent effects indicate that enzyme sensitivity to pressure depends on the solvent structure. This findings suggests that the substrate-dependent pressure effect is modulated by the solvation state of the enzyme.
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PMID:Conformational plasticity of butyrylcholinesterase as revealed by high pressure experiments. 226 67

We administered tetrahydroaminoacridine (THA), a cholinesterase inhibitor, to rats with bilateral nucleus basalis magnocellularis lesions and measured their performance in a spatial learning task. The subjects, 34 male Fischer-344 rats, received bilateral excitotoxic NBM lesions; 10 other rats served as unlesioned controls. Two weeks later the animals were tested in a circular water maze for time and distance swum to find a submerged platform. We tested three different doses (5.0, 2.5, and 1.25 mg/kg) of daily subcutaneous THA against a lesioned control group receiving saline and a fifth group of untreated unlesioned controls. The saline-treated lesioned group showed a significant impairment of acquisition. The 1.25 mg/kg group performed significantly better than the lesioned controls with respect to latency. Analysis of swim speed data showed slowing in the 2.5 and 5.0 mg/kg groups. Analysis of the distance swum to find the platform, an untimed task that corrects for the difference in swim speeds, showed statistically significant improvement in all three treated groups. Additionally, spatial memory for the platform location was improved by two of the three doses of THA tested. Passive avoidance retention was not impaired by our lesion. All lesioned groups had comparable reductions of cortical choline acetyltransferase. Our data show significantly improved spatial learning with THA. These data provide an additional rationale for further clinical testing of THA and other centrally active cholinergic agents in diseases with cholinergic loss.
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PMID:Tetrahydroaminoacridine improves the spatial acquisition deficit produced by nucleus basalis lesions in rats. 235 Dec 10

Electrolytic lesioning of the medial septum (MS) was used to assess the effectiveness of tacrine (THA) in reversing lesion-induced spatial memory deficits in a water-maze. Lesioned animals were injected with either 3 mg/kg or 5 mg/kg of THA intraperitoneally 15 min prior to daily behavioral training. One group of the lesioned and sham-operated animals received saline. All animals underwent two training trials each day for a period of ten days, after which a spatial probe trial was performed and assessed. The accurate placement of MS lesions resulted in lowered acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity within the hippocampus of lesioned rats. Lesioning of the MS also impaired the learning performance in locating the escape platform during training and decreased the spatial bias during the probe trial. A lower dose of THA (3 mg/kg) significantly reversed the path length increase and spatial bias decrease induced by MS lesioning, but had no effect on escape latency. However, comparison between the saline- and THA- (5 mg/kg) injected MS-lesioned rats showed no significant differences in either escape latency or spatial bias. The present results support the use of cholinesterase inhibitors in further treatment trials of geriatric memory disorders.
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PMID:The effects of THA on medial septal lesion-induced memory defects. 235 95

Eight days of treatment with two low doses of tetrahydroaminoacridine (THA), given once daily, substantially improved radial maze performance in two groups of rats which showed persistent deficits either after ibotenic acid lesions at the source of forebrain cholinergic projections, or after 28 weeks treatment with alcohol (20% v/v) in drinking water. However, in immature, aged or aged and alcohol-treated rats, acetylcholine content was not significantly affected in any of the brain areas measured, even though the treatment regime had proved behaviourally effective. Inhibition of brain acetylcholinesterase activity was only marginally increased by this treatment regime. Thus, if THA influences behaviour by enhancing cholinergic transmission, its effects do not appear to be related to its activity as a cholinesterase inhibitor, and alternative mechanisms of action should be investigated.
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PMID:Low dose tetrahydroaminoacridine (THA) improves cognitive function but does not affect brain acetylcholine in rats. 235 3

A novel water-soluble dopamine-2 antagonist, N-[4-[2-(dimethylamino) ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride (HSR-803) was synthesized and assayed for its gastrointestinal smooth muscle stimulating activity in vivo and in vitro. In the in vivo study, gastrointestinal contractile activity was measured by means of chronically implanted force transducers in conscious dogs; it was found that HSR-803 at 3.0 mg/kg IV probably stimulated gastric contractile force twice during the digestive state and significantly antagonized dopamine-(1.0 mg/kg per hour) inhibited gastric contractions in doses of 0.3, 1, and 3 mg/kg IV. With a background IV infusion of HSR-803 at 3 mg/kg per hour, the contraction-stimulating activity of acetylcholine (0.05 mg/kg per minute) was greatly enhanced while the response to bethanechol was not changed. As a result, HSR-803 was found to have a strong anticholinesterase activity besides the antidopamine-2 activity; i.e., the anticholinesterase activity of HSR-803 at 3 mg/kg per hour was equivalent to that of neostigmine at 10 micrograms/kg per hour, and dopamine-2 antagonistic activity of HSR-803 was similar to that of domperidone on a weight basis. No symptom suggesting actions on the central nervous system was noticed in HSR-803 up to 10 mg/kg IV in conscious dogs. In the in vitro study, HSR-803 inhibited cholinesterase dose-dependently, and IC50 was 2.9 x 10(-6) mol/L, while those of neostigmine and domperidone were 2.3 x 10(-8) mol/L and 1.7 x 10(-5) mol/L, respectively. In conclusion, HSR-803 stimulates endogenous acetylcholine release by antagonizing the dopamine-2 receptor on the postsynaptic cholinergic neurons, and the anticholinesterase activity of HSR-803 may cause the released acetylcholine to accumulate at cholinergic receptor sites. Thus, HSR-803 is potentially capable of enhancing cholinergic activity in the gastrointestinal region.
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PMID:A novel water-soluble dopamine-2 antagonist with anticholinesterase activity in gastrointestinal motor activity. Comparison with domperidone and neostigmine. 236 90

Organic phosphides such as insecticides and nerve gases are chemically and biologically akin. They have the same main structures and both act as cholinesterase inhibitors. The nerve gases are generally more reactively chemical and therefore far more toxic. Since both nerve gases and insecticides react to the same group of acetylcholinesterase the development of symptoms and the treatment of the intoxication are fairly similar. Intoxication may ensue from inhalation, from penetration of the skin, or from consumption of contaminated food or water. The latter mode of administration is the most common in cases of suicide.
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PMID:[Treatment of insecticide and nerve gas poisoning]. 236 90


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