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:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The preparation of ditertiary aliphatic diamines 3 designed as drugs protecting CNS acetylcholinesterase against organophosphate inhibition, is described. Owing to the radicals at the basic nitrogen atoms, these compounds should exist in appreciable amounts both as base and as diammonium ion at biological pH's.
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PMID:[Ditertiary diamine compounds (author's transl)]. 0 84

Interaction of usual effectors with acetylcholinesterase (EC 3.1.1.7) from bovine erythrocytes was examined under conditions of high ionic strength (gamma/2 greater than or equal to 0,1). Detailed kinetic investigation of the hydrolysis of acetylcholine by acetylcholinesterase in the presence of modifiers shows that the effects produced by numerous quaternary nitrogen compounds on the enzyme can be explained on the basis of binding of the effectors to the anionic subsite of the active center. The various kinetic behaviors, that are observed, are dependent on the relative values of the deacetylation rate constant ak of the complex acetylated enzyme-modifier and of the rate constant k-2 defined by : (see article) with respect to the value of the deacetylation rate constant K of the acetylated enzyme. If a identical to [1--(k/k-2)]-1, it is shown that interaction of the enzyme with tetraethylammonium, pentamethonium, hexamethonium and gallamine ions is characterized by : a greater than a and k-2 greater than k therefore, these modifiers accelerate deacetylation. On the other hand, inhibition of acetylcholinestase by methylpyridinium, d-tubocurarine, tetra-n-propylammonium, tetra-n-butylammonium, decamethonium and succinylbischoline is consistent with one of the conditions : a less than a and k-2 greater than or equal to k or a greater than a and k-2 less than k and inhibition by tetramethylammonium, phenyltrimethylammonium, 3-hydroxyphenyl-triethylammonium, N-methylacridinium and bis (3-aminopyridinium)-1,10-decane ions agrees with one of the two previous conditions or with : (see article) consequently, the effect of these ligands on the deacetylation step is undetermined. However, the effects of choline chloride, thiazinamium methyl sulfate and thioridazine hydrochloride are not entirely consistent with this mechanism but support the existence of a functional peripheral anionic site which is distinct from the anionic subsite of the active center.
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PMID:[Acetylcholinesterase. II. Experimental aspects of interaction with reversible effectors under conditions of high ionic strength]. 0 54

The multiple cholinesterase activities in canine platelets have been investigated. Platelets were homogenized by rapid decompression under nitrogen, glass tube/Teflon pestle, and glycerol lysis techniques. Rapid decompression under nitrogen technique was found to be the most efficient and gentle method for cell disruption. Homogenates were subfractionated using sodium diatrizoate density gradients. Marker enzyme assays and pulse labeling experiments with 5-hydroxyl[14C] tryptamine and [125I] thrombin on prepared subcellular fractions confirmed that the soluble, plasma membrane and the granule-1 fractions were all in reasonably pure form. Furthermore, labeling of the plasma membrane with [125I] thrombin is cited as the first successful attempt at attaining significantly bound marker for this structure. Cholinesterase activity distributions measured in these fractions indicated that about 30% of the activity was present in the plasma membrane, 50% in granule-1 and 5% in soluble fractions. Kinetic data of cholinesterase activities obtained from intact platelets, plasma membrane preparations and platelet release supernatants indicated that they are strikingly similar.
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PMID:The subcellular distribution and partial characterization of cholinesterase activities of canine platelets. 0 47

The present study reports of three kinds of experiments of unaffected primary rejection of xenogenous kidney transplanats in the close-related fox-dog species system. The issue is whether there is a relation between the amount of grafted parenchyma and the immune induced potency, that is whether the course of rejection of transplanted single kidneys (group I a) differs from the course after en-bloc transplantation of both kidneys (group I b). In group II alterations of blood chemism and behavior of humoral antibodies are followed in dogs to which a fox kidney was transplanted, while keeping their own functioning kidneys. This experiment is to give information whether the uremic syndrome influences the development of humoral immunity, and what changes of blood chemism may primarily be related to destruction of the graft, under the condition of absent uremia. Untreated graft recipients survived for 5,4 +/- 0,49 days (n = 5) when single kidneys were transplanted (group I a), and 5,2 +/- 0,75 days (n = 5) when both kidneys were grafted en-bloc (group I b). As to the rejecting reactions, both groups are almost equal: the increasing functional failure causes a fast increase of creatinine and urea nitrogen; alkaline phosphatase and LDH show distinct alterations, related to the progress of the graft's destruction. Decrease of albumin level and loss of cholinesterase activity indicate an impaired hepatic function as reaction to uremic intoxication. Gamma-globulins and leucocytes show alterations that can be related to non-specific inflammatory reactions. The immunologically specific initial lymphopenia suggests that after revascularization these cells migrate to the graft, and later react with antigenic structures of vascular endothelium and still later with those of the organ cells. Cytotoxic antibodies appear on the 4th postoperative day in increasing amount. Post mortem histologic examination shows round cell infiltrates in the vastly necrotic renal parenchyma. When the recipient's kidneys are kept in situ and a fox kidney is transplanted (group II) uremia is avoided and the animals survive. During the 30-days period of observation, that is longer than the term of rejection, the titer of cytotoxic antibodies remains stable or tends to increase. LDH and alkaline phosphatase show characteristic changes that are considered sequels from destructed transplantate. The experiments show, aside from certain reservations, that the donor-host combination fox-dog is suitable to serve as preclinic model for human transplantation using xenogenous donors of organs, i. e. anthropoid primates.
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PMID:[The unaffected primary rejection of xenogeneic kidney transplants in the closely related fox-dog species system]. 3 59

Ten male rhesus monkeys, each weighing 3.5 kg, were divided into four groups of 3, 3, 2, and 2, and were fed daily with 100 g pelleted food containing 300, 30, 3, and 0 ppm cadmium, respectively. Urine samples were collected every 2 weeks and blood samples every 4 weeks. One monkey each of the 300 and 30 ppm groups was autopsied for pathological examination and tissue cadmium determination at the week 24 of the experiment; the remaining 8 animals were killed after 55 weeks. The lowest exposed group (3 ppm) did not show any specific biological response to cadmium over a period of 55 weeks. In the 30 ppm group, no significant changes were observed for up to 24 weeks, although cadmium concentration in the renal cortex and urine at 24 weeks were 300 mug/g wet weight and 18 mug/l., respectively. Plasma urea nitrogen and urine protein (quantitative determination) increased after 30 and 36 weeks. At 55 weeks of the experiment, qualitative tests were negative for low molecular weight proteinuria and glycosuria, and the results remained normal for renal and liver function tests and blood analysis, although cadmium concentrations in the renal cortex of two monkeys were 460 and 730 mug/g wet weight and those in the liver were 110 and 160 mug/g wet weight, respectively. In the highest exposure group (300 ppm), urine cadmium increased to 250 mug/l. by 11 weeks, and urine retinol-binding protein, plasma GOT, GPT, and LDH increased after 12 weeks. Proteinuria (quantitative determination), glycosuria, aminoaciduria (panaminoaciduria), and erythrocytopenia were observed after 16 weeks, when urine cadmium was 500-900 mug/l. Hypohemoglobinopathy and proteinuria (qualitative determination) were observed after 20 and 24 weeks, while cadmium concentrations in the renal cortex and the liver were 760 and 430 mug/g wet weight at 24 weeks, respectively. Slightly depressed tubular reabsorption of phosphate, increased urine beta(2)-microglobulin, increased plasma urea nitrogen, and increased plasma alpha(2)-globulin fraction (electrophoresis) were observed between 28 and 30 weeks of the experiment. Creatinine clearance and plasma cholinesterase decreased after 47 and 54 weeks, respectively. Cadmium concentrations in the renal cortex and the liver of two monkeys at 55 weeks were 350 and 580 mug/g wet weight and 410 and 630 mug/g wet weight, respectively. Pathological examinations revealed denaturation, destruction, and regeneration of the epithelial cells in renal proximal tubules, but no pathological changes in osseous tissues. Critical cadmium concentration in the renal cortex was estimated to be 380 mug/g wet weight for low molecular weight proteinuria and 470 mug/g wet weight for proteinuria, glycosuria, and aminoaciduria. Critical concentration in the liver was also estimated to be 210 mug/g wet weight. The apparent biological half-time of cadmium in monkeys at autopsied stage was calculated to be 0.66, 6.4, 5.2, and 22.4 years for the 300, 30, 3, and 0 ppm groups, respectively.
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PMID:Effects of dietary cadmium on rhesus monkeys. 11 86

Seven pairs of monoquaternary enantiomeric neuromuscular junction blocking agents were prepared in which the carbon asymmetry is adjacent to the quaternized nitrogen moiety. The tertiary amines from which the blocking species were obtained are carnegine, laudanosine, N-methylpavine, corydine, isocorydine, glaucine, and boldine. Curarimimetic potencies, obtained with an in vivo cat tongue-hypoglossal nerve preparation, were obtained for the enantiomeric methiodides of each of these amines. Possible contributions to activity be preferential binding to blood components or by selective inhibition of acetylcholinesterase also were studied. The combined studies indicate that there is a modest preference by the neuromuscular junction of the cat for monoquaternary blockers with the (s)-confirguation.
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PMID:Stereochemical preferences for curarimimetic neuromuscular junction blockade I: enantiomeric monoquaternary amines as probes. 12 43

Eighteen compounds related to thiamine were assayed for their inhibitory potency against electric eel acetylcholinesterase at pH 7.00 and 8.25 by Ellman's method. Data in the form of progress curves were fitted to the integrated form of the rate equation for linear, mixed-type Michaelis-Menten kinetics. The values of Ki thus obtained were compared in order to define the loci of inhibition on the thiamine molecule. It was found that the positively charged quaternary nitrogen atom is the primary locus of inhibition, while alkyl groups in the molecule play a secondary role through hydrophobic association with the enzyme. Protonation of the inhibitors was seen to be an important factor.
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PMID:Inhibition of acetylcholinesterase by thiamine. A structure-function study. 55 74

A number of bis- and mono-N-substituted benzoquinolinium salts and their analogues were prepared and evaluated as inhibitors of acetylcholinesterase (AcChE) and butyrylcholinesterase (BuChE). These compounds were also used to help identify some of the morphologic characteristics of the surface at or near the active sites of the cholinesterases. The shape, size, configuration, and conformation of the onium moieties of the quaternary ammonium compounds were found to be the important factors in their anticholinesterase activity. A high concentration of the positive charge of the quaternary ammonium compound is not a critical factor for the cholinesterase inhibitory activity. The order of decreasing potency of cholinesterase inhibition of the benzoquinolinium compounds was found to be acridinium greater than phenanthridinium greater than 5,6-benzoquinolinium greater than 7,8-benzoquinolinium. The inhibitory activity of the monobenzoquinolinium halides against cholinesterases is influenced by the N-substituent. A bis-quaternary ammonium compound with a flexible bridge that links the two nitrogen atoms was found to be more potent in inhibiting AcChE and less potent in inhibiting BuChE than a bis-quaternary ammonium compound with a rigid bridge. The acridinium and phenanthridinium derivatives of the benzoquinolinium compounds are very potent reversible inhibitors against both AcChE and BuChE.
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PMID:Potent reversible anticholinesterase agents. Bis- and mono-N-substituted benzoquinolinium halides. 59 27

Blood from ten young adult male humans, exposed to 1 ppm or 2 ppm nitrogen dioxide (NO2) for 2.5--3.0 hr, was examined for evidence of biochemical changes. The experiments lasted three days. The subjects entered an environmental chamber, performed mild exercise, and completed a series of measurements of pulmonary physiology while breathing filtered air. Blood samples were then taken and analyzed. This regimen was repeated on the second and third day, except that the chamber atmosphere now contained 1 ppm or 2 ppm NO2. Paired group analyses were performed on the data. A statistically significant decrease was observed in the activity of the erythrocyte membrane enzyme acetylcholinesterase at both NO2 levels. Levels of peroxidized red blood cell lipids showed statistically significant elevations after inhalation of 2 ppm NO2 but not 1 ppm. Glucose-6-phosphate dehydrogenase was significantly elevated only after the second 2-ppm NO2 exposure. Small but statistically significant decreases were observed in both hemoglobin and hematocrit values after exposure to both NO2 levels. The experiment was repeated with NO2, (i.e., three days of filtered air) to detect possible effects of the experimental procedure. Decreases were again seen in hemoglobin and hematocrit, and acetyecholinesterase, although of smaller magnitude than when NO2 was inhaled. Other data showed random variations that were not additive over the three-day sham exposure period. It was concluded that significant blood biochemical changes resulted from NO2 inhalation, although the three-day experimental regimen independently produced changes that account for some of the apparent response.
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PMID:Nitrogen dioxide inhalation and human blood biochemistry. 73 16

A new cholinesteras reactivator--chlorohydrate of S-diethylaminoethyl ether p-bromo benzoylthiohydroxime acid (diethixime), containing a tertiary nitrogen atom in the molecule, was shown to produce a central effect in a dose of 20 mg/kg--1/50 LD50--in contrast to diproxime in a dose of 3 mg/kg, containing a quarternary nitrogen atom, under intoxication of albino rats and rabbits with dimethyl-dichlorynylphosphate. This effect was confirmed by the restortion of the cholinesterase activity in different parts of the rabbit brain, by the normalization of the EEGand of the functional stateof motor neurons of the rat spinal cord.
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PMID:[Effect of a new cholinesterase reactivator, diethixime, on the central nervous system]. 85 30


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