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)

One of the roles of astrocytes in the maintenance of perineuronal ionic balance during intense neuronal activity occurring after injection of convulsant agents like soman. Soman is an irreversible cholinesterase inhibitor and induces brain damage with early swelling of astrocytic perivascular processes. Mature astrocytes are easily characterized on freeze-fracture replicas owing to the presence of regular geometric aggregates of intramembranous particles: the 'orthogonal arrays' (OAs). In primary cultures of astrocytes OA distribution is homogeneous throughout the plasma membrane. A present hypothesis (see review in Risau and Wolburg, 1990) considers that these OAs are associated with channels controlling potassium ion concentration in the cerebral parenchyma. We have investigated the effects of extracellular concentrations of K+ ions identical to those observed during neuronal activity on primary cultures of astrocytes and effects induced by soman. High concentrations of K+ ions (60 mM) as well as soman exerted direct effects on astrocytic plasma membranes: K+ ion influx within astrocytes induces a partial disaggregation of OAs and more acutely than soman. Neither K+ ions nor soman induce swelling of astrocytic end-feet.
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PMID:Compared effects of extracellular K+ ions and soman, a neurotoxic, on cerebral astrocyte morphology. An in vitro study. 896 39

Clinically, neuromuscular blockade is induced with either depolarizing or non-depolarizing relaxants. Suxamethonium is the only depolarizing relaxant still in use. It is hydrolysed in the plasma by pseudo-cholinesterase (plasma cholinesterase). In some patients and in particular diseases the plasma cholinesterase activity is low and hence the effect of suxamethonium prolonged. Suxamethonium is characterized by side-effects such as myalgia, fasciculations and increase in intraocular, intracranial and intragastric pressure. More serious adverse reactions are masseter muscle spasm and potassium release, in patients with some neuromuscular diseases and increase in extrajunctional acetylcholine receptors. As non-depolarizing muscle relaxants benzylisoquinolines and steroidal compounds are mainly used. Each relaxant has its own pharmacological characteristics. The effect of most relaxants depends on liver and renal function because the pharmacokinetic behaviour is strongly dependent on these organs. Also, acid base balance disturbances, change in temperature, and neurological diseases have an effect on the profile of the relaxants. A number of drugs (anaesthetics, antibiotics, antiepileptics, etc.) have an effect on neuromuscular transmission, and thus interact with the relaxants. Some non-depolarizing relaxants cause histamine release and cardiovascular effects.
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PMID:Neuromuscular transmission and its pharmacological blockade. Part 2: Pharmacology of neuromuscular blocking agents. 908 50

To investigate the spinal cellular structures and molecular mechanisms involved in acetylcholinesterase (AChE) release evoked by both glycine (GLY) and glutamate (GLU)--responses that might play a role in chronic neurotoxicity--we analysed AChE histochemistry and histology upon systemic administration of aspartate (ASP), and conducted in vitro experiments in synaptosomes and slices prepared from mouse spinal ventral horns. Upon superfusion and incubation exposure of these preparations to GLY- and GLU-receptor agonists, we assayed both tissue content and release of AChE, butyrylcholinesterase and lactic dehydrogenase. Histochemical reduction of motor neurone (MN) AChE, calcium dependency, decreases in intracellular AChE and the ratio amongst molecular forms released, suggest that both synaptosomal GLY-evoked AChE release (GLY-EAR) and GLU-receptor-elicited AChE release (GEAR) have release sites located at MN presynaptic terminals. These responses exhibited remarkable postnatal regulation. GEAR seems to be mediated through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptors after the fourth postnatal week and through both NMDA and non-NMDA receptors at earlier stages. Sustained rises of extracellular AChE might link acute excitotoxic injury with several long-lasting pathways leading to chronic neurotoxicity, since AChE molecular properties include: (1) the ability to block cholinergic mechanisms that protect MN against overactivity; (2) activation of ATP-dependent potassium channels; (3) promotion of neurite and axon outgrowth; and possibly (4) stimulation of brain macrophage migration and activation.
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PMID:In vivo and in vitro studies of glycine- and glutamate-evoked acetylcholinesterase release from spinal motor neurones: implications for amyotrophic lateral sclerosis/motor neurone disease pathogenesis. 941 55

1. The toxic gas hypothesis proposes exposure to stibine (antimony trihydride) generated from microbial contamination of cot mattress materials as a possible cause of unexplained death in infancy (SIDS) as a consequence of cholinesterase inhibition. We have measured the direct effects of antimony compounds including stibine on the activity of plasma cholinesterase, red blood cell acetylcholinesterase (AChE) and mouse neuronal AChE in vitro. 2. Colorimetric assays for the different esterases with potassium antimonyl tartrate or antimony trichloride at concentrations up to 10(-3) M in the presence of substrate concentrations sufficient to produce 80% of the maximum reaction rate produced no inhibition of enzyme activity. Exposure of enzyme preparations to stibine gas at concentrations sufficient to cause denaturation of red cell haemogloblin caused no measurable inhibition of esterase activity. 3. We conclude that stibine gas or soluble antimony compounds are not capable of inhibiting cholinesterase activity at toxicologically relevant concentrations.
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PMID:Lack of inhibition of human plasma cholinesterase and red cell acetylcholinesterase by antimony compounds including stibine. 958 81

Concentrations of 34 biochemical constituents of sera were determined on 998 randomly selected urban school children and adolescents aged 8-18 years from Zagreb, Croatia. Reference intervals were obtained by using non-parametric methods to estimate 2.5 and 97.5 percentiles of distribution as upper and lower normal reference intervals, according to the IFCC recommendations. These were compared to reference intervals in the healthy adult population, aged 20-30 years from the same geographical area. Serum glucose, potassium, sodium, chloride, magnesium, iron, zinc, total serum proteins and electrophoretic fractions, and amylase, did not show age or sex differences; total serum bilirubin, total calcium, phosphate, high density lipoprotein cholesterol, total iron binding capacity, unsaturated iron binding capacity, copper, aspartate aminotransferase, alkaline phosphatase, cholinesterase, creatine kinase, and lactate dehydrogenase had higher reference intervals than the adult population. Urea, creatinine, urate, alanine aminotransferase, gamma-glutamyltransferase, total cholesterol and low density lipoprotein-cholesterol, and triglycerides had lower reference intervals than the adult population.
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PMID:Pediatric reference intervals for 34 biochemical analytes in urban school children and adolescents. 967 91

The effects of possible activators of soluble guanylate cyclase were studied. Hydroxylamine and some oxime derivatives such as pyridinium aldoximes and bispyridinium dioxime (dipyroxime) were tested as possible guanylate cyclase activators. These compounds are known to be reactivators of choline esterase which has been preinhibited with phosphoorganic compounds. All the tested compounds were found to activate human platelet guanylate cyclase in the concentration range 10-6-10-3 M. The highest stimulatory affect was achieved at 10-4 M with hydroxylamine and dipyroxime: 210 +/- 10 and 320 +/- 15%, respectively. Potassium ferricyanide oxidation of these compounds under mild conditions formed nitroprusside ion, as registered by the electrochemical (polarographic) method; this is evidence that these compounds are NO donors. It is concluded that the activation of guanylate cyclase by the tested compounds is associated with their ability to generate NO during their biotransformation. The possible role of guanylate cyclase activation by oxime derivatives in the mechanism underlying the reactivation of inhibited choline esterase at the cell level is discussed.
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PMID:Role of soluble guanylate cyclase in reactivation of choline esterase inhibited by phosphoorganic compounds. 998 19

The hippocampus is importantly involved in learning and memory, and is severely impacted by aging. In in vitro hippocampal slices, both the post-burst afterhyperpolarization (AHP) and spike-frequency accommodation are reduced in hippocampal pyramidal neurons after hippocampally-dependent trace eyeblink conditioning, indications of increased cellular excitability. The AHP results from the activation of outward potassium currents, including sI(AHP) and muscarine-sensitive I(M). The AHP is significantly increased in aging hippocampal neurons, potentially contributing to age-associated learning deficits. Compounds which reduce the AHP and spike-frequency accommodation could facilitate learning in normal aging or in age-associated dementias such as Alzheimer's disease. The cholinesterase inhibitor metrifonate enhances trace eyeblink conditioning by aging rabbits and reduces the AHP and accommodation in hippocampal CA1 neurons in a dose-dependent manner. These reductions are mediated by muscarinic cholinergic transmission as they are blocked by atropine. Hippocampal neurons from metrifonate treated but behaviorally naive rabbits were more excitable and not desensitized to the effects of metrifonate since the AHP and accommodation were further reduced when metrifonate was bath applied to the neurons. These observations suggest that the facilitating effect of chronic metrifonate on acquisition of hippocampally dependent tasks is mediated at least partially by increasing the baseline excitability of CA1 pyramidal neurons. The issue of whether learning can be facilitated with muscarinic cholinergic agonists, in addition to cholinesterase inhibitors, was addressed by training aging rabbits during intravenous treatment with the M1 agonist CI1017. A dose-dependent enhancement of acquisition was observed, with rabbits receiving 1.0 or 5.0 mg/ml CI1017 showing comparably improved learning rates as those receiving 0.5 mg/ml or vehicle. Sympathetic side effects, mainly excess salivation, were seen with the 5.0 mg/ml dose. Post-training evaluations suggested that the effective doses of CI1017 were enhancing responsivity to the tone conditioned stimulus. These studies suggest that muscarinic cholinergic neurotransmission is importantly involved in associative learning; that learning in aging animals may be facilitated by enhancing cholinergic transmission; and that the facilitation may be mediated through actions on hippocampal neurons.
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PMID:Cholinergic facilitation of trace eyeblink conditioning in aging rabbits. 1006 21

Chronic toxicity and carcinogenicity of polyoxyethylene(10)nonylphenyl ether (NP-10) to Fischer 344 rats were investigated using 70 females per group in 4 study groups, or 280 rats in total. Diets containing NP-10 at 0, 1000, 3000 and 9000 ppm were prepared and orally administered to the animals repeatedly for 52 weeks for a chronic toxicity study and for 104 weeks for a carcinogenicity study. Observations of general condition, body weight analysis, food consumption analysis, hematologic examination, blood chemistry examination (only at Week 52 of administration), urinalysis (only at Week 52), ophthalmologic examination (immediately prior to administration and at Week 52), organ weight analysis and pathological examination were performed. The results are summarized as follows. The mean intake of the test substance was 60.5, 182 and 559 mg/kg/day in the chronic toxicity study for 52 weeks and 55.2, 166 and 520 mg/kg/day in the carcinogenicity study for 104 weeks in the 1000, 3000 and 9000 ppm groups, respectively. Mortality decreased approximately in a dose-related manner, with 28% in the control group, 26% in the 1000 ppm group, and 14% each in the 3000 and 9000 ppm groups. In general condition, there were no signs attributed to the treatment with NP-10. Body weight gain was suppressed in the 9000 ppm group throughout the administration period and in the 3000 ppm group during Weeks 21-88. Food consumption decreased in the 9000 and 3000 ppm groups. Food efficiency was lower in the 9000 and 3000 ppm groups. As a result of the hematologic examination, hematocrit value, hemoglobin value, red blood cell count, platelet count and MCV were lower and MCH and MCHC higher in the 9000 ppm group at Week 52 of administration. At Week 104, the neutrophil ratio was higher and lymphocyte ratio lower in the 3000 and 9000 ppm groups, and furthermore, hematocrit value, hemoglobin value, MCV and MCH were slightly lower in the 9000 ppm group. In the blood coagulability tests, prothrombin time was slightly shortened in the 9000 ppm group at Week 52. As a result of the blood chemistry examination, total protein and albumin values were higher and total bilirubin, uric acid and trygliceride value lower in the 3000 ppm and higher dose groups. Furthermore, the free cholesterol value was higher and the values of potassium, cholesterol ester ratio, GOT, GPT, ALP and cholinesterase were lower in the 9000 ppm group. As a result of the urinalysis, the specific gravity of urine was higher and urine pH acidic in some animals. As a result of the ophthalmologic examination, no abnormal animals were found in the 9000 ppm group. As a result of the organ weight analysis, absolute and relative weights of the liver and adrenals were higher in the 3000 and/or 9000 ppm groups as changes which were considered attributable to the test substance and, in addition, organs with a lower absolute weight and higher relative weight with the suppressed body weight gain were observed in the 9000 ppm group. The histopathological examination revealed no marked findings in necropsy observation or histology in the treated groups in the animals killed at Weeks 52, 104 as well as those killed moribund and dead animals. In the histological findings, bile duct hyperplasia of liver in the animals killed at Week 52, proliferative duct of pancreas in the animals killed at Week 104, pigment of deposit in pituitary and angiectasis of adrenals in the animals killed at moribund and dead animals were observed in a slightly larger number in the treated groups, but none of these changes were different in degree from the control and were not considered to be specific lesions. As a result of the overall study of the neoplastic lesions of all animals killed on schedule and of moribund and dead animals, no tumors were found in the treated groups which had increased in occurrence. Based on the above findings, it was determined that the no-adverse-effect level in the chronic toxicity study was 1000 ppm (
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PMID:Oral chronic toxicity and carcinogenicity test of polyoxyethylene(10)nonylphenyl ether (NP-10) in female F344 rats. 1066 63

The effects of the cholinesterase inhibitor neostigmine on the responses to vagus nerve stimulation of isolated sinus venosus/atrial preparations of the toad, Bufo marinus, were examined. In control solutions, trains of stimuli applied to the vagus nerve led to a decrease in heart rate that was susceptible to muscarinic receptor blockade. Membrane potential recordings made from sinus venosus cells showed that the responses to trains of stimuli, delivered at frequencies of less than 10 Hz, were little changed by the addition of neostigmine. However, the responses to longer trains of stimuli at 10 Hz (30 versus 10 s) were potentiated and the nature of the membrane potential changes was altered. The results suggest that, due to the activity of cholinesterases, acetylcholine (ACh) released from parasympathetic nerves normally has little access to the muscarinic receptors in the pacemaker region, which are linked to potassium channels.
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PMID:Potentiation by neostigmine of responses to vagal nerve stimulation in the sinus venosus of the toad. 1102 16

Metrifonate, a cholinesterase inhibitor, has been shown to enhance learning in aging rabbits and rats, and to alleviate the cognitive deficits observed in Alzheimer's disease patients. We have previously determined that bath application of metrifonate reduces the spike frequency adaptation and postburst afterhyperpolarization (AHP) in rabbit CA1 pyramidal neurons in vitro using sharp electrode current-clamp recording. The postburst AHP and accommodation observed in current clamp are the result of four slow outward potassium currents (sI(AHP), I(AHP), I(M), and I(C)) and the hyperpolarization activated mixed cation current, I(h). We recorded from visually identified CA1 hippocampal pyramidal neurons in vitro using whole cell voltage-clamp technique to better isolate and characterize which component currents of the AHP are affected by metrifonate. We observed an age-related enhancement of the slow component of the AHP tail current (sI(AHP)), but not of the fast decaying component of the AHP tail current (I(AHP), I(M), and I(C)). Bath perfusion of metrifonate reduced sI(AHP) at concentrations that cause a reduction of the AHP and accommodation in current-clamp recordings, with no apparent reduction of I(AHP), I(M), and I(C). The functional consequences of metrifonate administration are apparently mediated solely through modulation of the sI(AHP).
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PMID:Metrifonate decreases sI(AHP) in CA1 pyramidal neurons in vitro. 1115 31


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