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)

Phencylidine derivatives exhibit multiple interactions with cholinergic systems: they block nicotinic and muscarinic receptors,and inhibit both acetyl and butyrylcholinesterase. In peripheral tissue, the net pharmacological effects of the phencyclidines is antiacetylcholine activity. The dissociation constants measured in isolated smooth muscle and from competition experiments for the muscarinic high-affinity binding sites in brain homogenates (Kd = 10(-5) - 10(-6) M) are 3--4 orders of magnitude lower than those of anticholinergic glycolate esters. However, phencyclidines have comparable potency to that of d-tubocurarine in blocking the nicotinic receptor in the isolated frog rectus abdominis (Kd = 10(-6) M). Brain uptake experiments of (3H) labeled phencyclidine showed that during the time period in which central effects are observed with these drugs their concentration in brain reaches values close to the Kd (10(-5) - 10(-6) M). This finding, and the cross tolerance observed in vivo between phencyclidine and other centrally acting cholinergic drugs supports the possible involvement of cholinergic interactions in the psychotropic action of phenyclidine derivatives. Quantum chemical calculations of the interaction pharmacophores of drugs in the phencyclidine series have indicated the molecular determinants for the interaction of these drugs with the muscarinic receptor. The calculations revealed that these drugs can match the reactivity characteristics of ACh and the semi-rigid muscarinic agonist 3-acetoxyquinuclidine, but their rigid molecular frame will be conductive to antagonistic rather than agonistic activity when the drug-receptor complex is formed. The identification of a "cholinergic interaction pharmacophore" for these drugs by quantum mechanical calculations made possible the suggestion of other active phencyclidine derivatives, e.g. p-NH2 and p-OH analogs which proved to be equipotent to phencyclidine. The inactivity of the p-NO2 derivative was also predicted on this basis and served as an additional confirmation of the theoretical criterion for activity; the difference between the activities of the ethynyl and cyano derivatives was explained by the modification of the cholinergic interaction pharmacophore. On the basis of these theoretical predictions, electrophysiological studies were carried out by the others and the results prompted the suggestion that "physostigmine is of potential value in the treatment of post-operative patients emerging from ketamine anesthesia and in the treatment of phencyclidine overdosed patients".
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PMID:Some structure activity relationships of phencyclidine derivatives as anticholinergic agents in vitro and in vivo. 42 35

In order to gain insight into the possible role of the ACh-system in the smooth muscle cell, the presence of choline acetyltransferase, acetylcholinesterase and butyrylcholinesterase was studied in the longitudinal muscle of the guinea-pig ileum after the mechanical removal of Auerbach's plexus. Such treatment completely removes all nerve elements as confirmed by histochemistry and electron-microscopic examination. It was found that in the longitudinal muscle devoid of all nervous elements a substantial percentage of the activity of all three enzymes still remained. Ultrastructural localization of acetylcholinesterase and butyrylcholinesterase was observed on the sarcolemma, sarcoplastic reticulum, nuclear membrane and invaginations of the sarcolemma. The localization of cholinesterases coincides with sites which are presumably involved in calcium movements during contraction and relaxation. It is well known that the depolarized smooth muscle responds to exogenous ACh with a reversible, calcium dependent contraction and it was suggested that ACh may act by increasing the influx of calcium through the cell membrane or by liberating calcium from its bound form. The presence of choline acetyltransferase and cholinesterase activities in the muscle cell proper, as well as the localization of cholinesterases on structures connected with calcium movements, support the coexistence of an intrinsic cholinergic mechanism in the smooth muscle.
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PMID:Cholinesterases and choline acetyltransferase in the longitudinal muscle of the guinea pig ileum. 51

The effects of methylmercury chloride and other mercury compounds on cholinergic parameters were studied in vitro. Methylmercury chloride (MMC) and phenylmercury acetate inhibited choline acetyltransferase (ChA) with 20 microM of I50, and mercury nitrate (MN) with 100 microM of I50. All the three compounds had little effect on cholinesterase activity. MMC inhibited a high affinity choline uptake with 41 microM of Ki, as well as a low affinity choline uptake with 250 microM of Ki. MMC did not affect a spontaneous and potassium-stimulated ACh release from brain tissue slices incubated in eserinized Krebs-Ringer's solution up to the concentration of 100 microM. It was shown that the organic mercury compounds, such as methylmercury, were potent inhibitors of the choline uptake systems, as well as ChA activity.
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PMID:Effects of methylmercury chloride on various cholinergic parameters in vitro. 54 84

Specific and non specific cholinesterase activities were demonstrated in the ABRM of Mytilus edulis L. and Mytilus galloprovincialis L. by means of different techniques. The results were found identical for both species: neuromuscular junctions "en grappe"-type scarely distributed within the ABRM, contain AChE. According to the histochemical inhibition tests, (a) the eserine inhibits AChE activity of the ABRM with a level of 5-10(-5) M or higher, (b) the ChE non specific activities are inhibited by iso-OMPA level between 5.10(-5) to 10(-4) M. The histo- and cytochemical observations were completed by showing the existence of neuromuscular junctions containing small clear vesicles: they probably are the morphological support for ACh presence. Moreover, specific and non specific ChE activities were localized in the glio-interstitial cells. AChE precipitates were developed along the ABRM sarcolemma, some muscle mitochondria and in the intercellular spaces remain enigmatic.
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PMID:[Innervation of the anterior byssus retractor muscle (ABRM) in Mytilus edulis L. and in Mytilus galloprovincialis Lmk. V. Cytochemical localization of cholinesterase activities (author's transl)]. 64 Aug 63

25 iodomethylates of acetic, propionic, butyric, isobutyric and valeric esters of N-(beta-hydroxyethyl)-derivatives of ephedrine (I) pseudo-ephedrine (II), salsoline (III), salsolidine (IV) and cytisine (V) are studied as substrates and inhibitors of acetylcholine esterase (EC 3.1.1.8) from human erythrocytes and butyrylcholine esterase (EC 3.1.1.8) from horse serum. Butyrylcholine esterase found to increase the hydrolysis rate of all the alkaloid esters studied with the increase of acyl radical either to valerates (for ephedrine and pseudo-ephedrine derivatives), or to butyrates (for the rest alkaloids) and then it did not considerably change under further elongation of carbon chain up to valerate. Isobutyrates were observed to be similar to propionates in their hydrolysis rates. Acetylcholine esterase hydrolyzed acetates with the highest rate, while butyrates of ephedrine and pseudoephedrine derivatives were hydrolyzed by the enzyme 2,5-3-fold as slow as acetates. The rate of choline esterase hydrolysis decreased in the row: ephedrine--salsoline--cytisine with the volumetric increase of the cationic group. The decrease was almost 10-fold for butyrylcholine esterase, while a transition from "poor" substrates to reversible inhibitors was observed for acetylcholine esterase (3 of 5 cytisine esters were reversible inhibitors of the enzyme). The data obtained are compared with literary data on other cyclic choline esterase substrates; they are discussed from the viewpoint of unproductive binding hypothesis and on the basis of the structure of active centres of acetyl- and butyrylcholine esterases.
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PMID:[Ephedrine, salsoline and cytisine derivatives as substrates and inhibitirs of cholinesterases]. 69 1

Four methods for measuring serum cholinesterase activity have been applied to sera of normal individuals and of patients shown to be sensitive to short-acting muscle relaxants of the succinyldicholine type. They have been assessed according to their ability to differentiate between sensitive and insensitive individuals on the basis of enzyme activity measurements alone. The method described, based upon that of Dietz et al. [Clin. Chem. 19, 1309 (1973)], in which propionylthiocholine is used as substrate, is best for this purpose, being capable of identifying over 90% of affected individuals with no false positives. Acetylcholine and butyrylthiocholine are slightly inferior substrates in this respect, and benzoylcholine gives little useful information.
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PMID:Is serum cholinesterase activity a predictor of succinyl choline sensitivity? An assessment of four methods. 69 86

Acetylcholine (ACh) content of the central nervous system in the sipunculid P. japonicum was estimated by application of extracts from the nervous tissue to dental retractor of the sea urchin using ACh solutions with known concentration as a standard. It was shown that the nervous tissue contains 46 (from 41 to 51) microng of ACh (calculated as cation) per 1 g of wet material. In the presence of the nervous homogenate from Physcosoma, 880 micronM of ACh are hydrolyzed by 1 g of wet tissue per 1 hour. The content of ACh and the activity of cholinesterase are comparable with those in the brain of molluscs, arthropods and mammals. Anticholinesterase drugs (physostigmine and neostigmine) evoked spontaneous contractions of the proboscis retractor when applied to the nervous cord and enhanced the response of this muscle to electrical stimulation of this cord. Cholinolytics (arpenal and pentaphen) also caused spontaneous muscle contractions, but prevented the increase in muscular activity in response to electrical stimulation in presence of physotigmine. The data obtained suggest cholinergic nature of the transmission in the central nervous system of sipunculids.
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PMID:[Cholinergic mechanisms in the central nervous system of the sipunculoid Physcosoma japonicum]. 86 96

The morphology of motor end-plates in rabbits immunized with Torpedo nicotinic acetylcholine receptor (nAChR) has been studied by light and electron microscopy. Rabbits were studied either after one period of paralysis, some in parallel with electrophysiological recordings of MEPPs and EPPs and of Naja naja alpha-neurotoxin binding properties or after recovery followed by a second paralysis. Changes in the sub-neural apparatus were noted after cholinesterase staining only in the latter group. Ultrastructurally, however, most end-plates in both groups contained a wide range of abnormalities. Many were similar in appearance to those observed in human myasthenia gravis (MG). This further supports the theory that immunized rabbits can be used as a model for myasthenia gravis. In the rabbits with 1 period of paralysis an acute stage of influence on the neuromuscular junction seemed to be present while simplified motor end-plates typical for human MG were mostly found in rabbits with 2 periods of paralysis. Short post-synaptic folds in conjugation with thickeneed membrane-bound vesicles at their tops, inside the basement membrane, were frequently observed. These were interpreted as if the crests of the folds containing nAChR had degenerated and had been budded off. If so, a large number of receptor sites had been lost which would be one possible explanation for the lowered capacity of the muscles to bind Naja naja alpha-neurotoxin. Membrane thickenings with projections and striations were interpreted as reflecting ACh receptors and were observed in the post-junctional membrane without proximity to the nerve terminal. The degeneration of the top of the post-synaptic folds and the occurrence of receptors at other locations within the motor end-plate will result in a widened distance between the nerve terminal and the receptors, which can explain previous interpretations of a presynaptic defect in MG.
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PMID:Morphological observations on motor end-plates in rabbits with experimental myasthenia. 97 17

The effect of eight monoquaternary and bisquaternary pyridine aldoxime cholinesterase reactivators was tested on isolated guinea-pig heart atria. 2. Acetylcholine and methylfurthretonium in concentrations ranging from 10(-7) M to 10(-5) M have negative inotropic effects in the electrically stimulated atria and negative chronotropic effects in the spontaneously beating atria. 3. In the presence of higher concentration of cholinesterase reactivators alone, the parameters of heart muscle contractility are significantly altered. 4. Cumulative dose-response curves of methylfurthretonium in the presence of reactivators in the range of concentrations from 10(-5) M to 10(-3) M are shifted parallelly to higher concentrations of the agonist.
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PMID:The effects of some cholinesterase reactivators on contractility of the isolated guinea-pig heart atria. 98 15

1. Rabbit retinas were isolated and superfused with a physiological medium. Ganglion cell activity was recorded during stimulation with focused light, and receptive fields were mapped. Receptive fields were identical to those found in vivo and did not change during a 6-h incubation. After the receptive field of a ganglion cell had been identified, acetylcholine or related agents were introduced singly or in combination into the medium, and their effect on the cell's spontaneous and light-evoked activity was observed. 2. Ganglion cells with on-center or directionally selective receptive fields were excited when ACh was added to the medium. The response to exogenous ACh was prevented by cholinergic antagonists. 3. These cells' spontaneous activity and response to light were enhanced by anticholinesterase and depressed by cholinergic antagonists. Antagonists varied in their ability to block the light-evoked response, with dihydro-beta-erythroidine the most effective. 4. Thresholds for ACh or the related agents were low, ranging from 1 to 40 muM; their effects were rapidly and completely reversed when the retina was returned to control medium. 5. In retinas incubated in medium containing 20 mM Mg2+ and 0.2 mM Ca2+, ganglion cells lost completely both their spontaneous and light-evoked activity, but retained their ability to generate action potentials in response to elevated K+. Ganglion cell activity rapidly returned to normal when the retina was returned to medium containing normal electrolytes. On-center and directionally selective cells were excited by ACh in retinas where synaptic transmission had been inhibited by 20 mM Mg2+ and 0.2 mM Ca2+. 6. The responses of on-center and directionally selective cells to ACh, to anticholinesterase, and to cholinergic antagonists in control medium indicate that the retina contains one or more synapses using ACh as a neurotransmitter. The response to ACh in retinas exposed to 20 mM Mg2+ and 0.2 mM Ca2+ suggests that at least one such synapse in on the ganglion cell itself. 7. Off-center cells were inhomogenous in their response to ACh. Although some responded just as the other classes of cell, the majority responded quite weakly and a subgroup was encountered which was entirely unaffected by even 1 mM ACh, by levels of physostigmine which inactivate virtually all retinal acetyl-cholinesterase, or by high concentrations of cholinergic antagonists. Only 2 of 20 off-cells tested in the presence of 20 mM Mg2+ and 0.2 mM Ca2+ were excited by ACh. Apparently ACh is not a primary transmitter for most off-cells.
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PMID:Responses to acetylcholine of ganglion cells in an isolated mammalian retina. 99 29


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