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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)

We have studied the physicochemical properties of acetylcholinesterase (AChE) during embryonic development of normal and functionally impaired mouse skeletal muscle, focusing on the tailed asymmetric (16S) form of the enzyme. The muscle-specific 16S AChE exists in two different variants. One is associated with extracellular matrix and is high-salt soluble (HSS, also termed hydrophilic AChE), whereas the other form is anchored to cell membranes and is detergent extractable (DE, or hydrophobic AChE). Before innervation during normal embryonic development, both hydrophilic and hydrophobic 16S AChE exist in equal amounts. After muscle innervation, there was an increase (amounting three-fold on E18) in the levels of hydrophilic vs. hydrophobic 16S AChE. This alteration of the relative proportions of the two variants of 16S AChE did not occur in chronically inactive muscles either from the mouse mutant, muscular dysgenesis, or from tetrodotoxin-treated mouse embryos. Taken together with previous reports, the present results suggest that postsynaptic membrane depolarization-induced Ca2+ fluxes are important in modulating not only the synthesis of 16S AChE, but also the relative proportions of both physicochemical variants of this molecular form of AChE.
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PMID:Developmental modulation of physicochemical variants of the tailed asymmetric (16S) acetylcholinesterase by neuromuscular activity and innervation in the mouse embryo. 189 Jul 3

Calcium (Ca2+) and calcium-transporting ionophores stimulate protein secretion in many cellular systems. We demonstrate here than increases in intracellular calcium concentration induce a time- and concentration-dependent deposition of extracellular matrix and an increase in acetylcholinesterase secretion. Scanning and transmission electron-microscopy revealed that treatment with the calcium ionophore A23187, or high extracellular Ca2+ levels (5 mM to 15 mM) produce significant deposits of extracellular matrix around the myotubes, as well as a marked increase in the acetylcholinesterase reaction-product. Blocking muscle contraction was not necessary for the induction of AChE secretory activity. Sucrose density-gradients of media conditioned by muscle cells revealed 3 separate acetylcholinesterase molecular forms. However, incubation with A23187 increased only the 4.5 S and the 7.2 S molecular forms, whereas the 12.0 S form showed no significant differences from controls. Polyacrylamide gel electrophoresis, and autoradiography using [3H]diisopropyl fluorophosphate revealed a broad band at 65,000 daltons. This band was broader than for controls when medium was obtained from A23187-treated cells. Our results show that increasing intracellular Ca2+ concentration induces marked deposition of extracellular matrix and increased acetylcholinesterase secretion, with an apparent selectivity for the monomeric and dimeric acetylcholinesterase molecular forms.
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PMID:Calcium and ionophore A23187 stimulates deposition of extracellular matrix and acetylcholinesterase release in cultured myotubes. 191 83

Ganglionic effects of the histamine H2 receptor antagonists cimetidine, ranitidine and 1-nitro-2-(2-propynylamino)-2-(2-[dimethylaminomethyl-2-furanyl) methylthiol]-ethylamino)ethylene (ORF 17578) were compared in the isolated superior cervical ganglion of the rat. Extracellular recording of compound action potentials showed that the drugs caused concentration-dependent inhibition of ganglionic transmission, as indicated by depression of the postganglionic compound action potential. Cimetidine-induced inhibition of ganglionic transmission was stimulus frequency-dependent. Increasing the Ca2+ from 2.2 to 4.4 mM in the bathing solution did not significantly affect the inhibitory actions of these agents. In the series with ranitidine, pretreatment with DFP to inhibit acetylcholinesterase similarly had no significant effect on the depression of the compound action potential by ranitidine. All three agents had little or no effect on nerve conduction in isolated vagi of the rat. The results indicate that all three histamine H2 receptor blockers inhibited ganglionic transmission, but only in large concentrations. The results also suggest that the blocking effect of these drugs was unrelated to their reported anticholinesterase action or to blockade of histamine H2 receptors, which are believed to exist on the presynaptic membrane. It is suggested that the ganglion effect may be due to the action of these agents on the acetylcholine receptor-ion channel complex in the postsynaptic membrane.
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PMID:A comparative study of the actions of histamine H2 receptor antagonists on transmission in the isolated superior cervical ganglion of the rat. 197 Jan 32

Diagnostic electrocardiostimulation (ECS) of the right atrium with evaluation of the functional state of the heart conduction system and coronary reserve was carried out in 177 patients. The level of blood catecholamines, activity of cholinesterase and content of destroyed acetylcholine, cortisol, free fatty acids, glucose, insulin, thyroxine, triiodothyronine, renin, testosterone, calcium was determined before and at the height of diagnostic ECS. In cases with a tendency to bradycardia one could note compensatory tension of the sympathetic-adrenal system and mechanisms of general adaptation. In organic weakness of the sinus node with stable bradysystole there were signs of exhaustion of the adrenal reserves of catecholamines and cortisol manifested in paradoxic reduction of them in the blood in response to frequent ECS and corresponding changes of energy provision.
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PMID:[The neurohumoral regulation and energy support of the myocardium in patients with heart rhythm disorders]. 197 44

In the present investigations, we used a superfusion system to study the effect of simultaneous activation of D2 dopamine receptors and so-called muscarinic "autoreceptors" on the K(+)-evoked in vitro release of [3H]acetylcholine from rat striatal tissue slices. Activation of D2 receptors with the selective agonist LY 171555 (0.01-1 microM) clearly decreased the evoked release of [3H]acetylcholine. This effect was markedly attenuated in the presence of either the selective muscarinic receptor agonist oxotremorine (3 microM) or the cholinesterase inhibitor physostigmine (1 microM). Conversely, D2 receptor activation with LY 171555 (1 microM) completely abolished the muscarinic receptor mediated inhibition of evoked [3H]acetylcholine release induced by oxotremorine (0.03-10 microM). These results show that the inhibitory effects of D2 dopamine receptor and muscarinic receptor activation on striatal acetylcholine release are non-additive and therefore are interdependent processes. In addition, we investigated some aspects of the signal transduction mechanism by which the muscarinic receptor mediates inhibition of K(+)-evoked in vitro release of [3H]acetylcholine from rat striatal tissue slices. It appeared that the effect of muscarinic receptor activation was not significantly influenced either by a lowering of the extracellular Ca2+ concentration from the usual 1.2-0.12 mM or by an increase of the intracellular cyclic adenosine-3',5'-monophosphate content. However, increasing extracellular K+ strongly decreased the inhibition of evoked [3H]acetylcholine release mediated by activation of muscarinic receptors. This set of results indicates that the muscarinic "autoreceptor" mediates the decrease of depolarization induced [3H]acetylcholine release from rat striatum to a large extent through stimulation of K+ efflux (opening of K+ channels) in a cyclic adenosine-3',5'-monophosphate independent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscarinic receptor activation attenuates D2 dopamine receptor mediated inhibition of acetylcholine release in rat striatum: indications for a common signal transduction pathway. 197 37

(1) Microsomal membranes from white rabbit muscle enriched in sarcoplasmic reticulum (SR) were used to investigate the preferential localization of acetylcholinesterase (AChE) in these membranes. (2) Integrity and orientation of the vesicles was assessed by measuring the inulin-inaccessible space of the vesicles and its calcium-loading capacity. (3) Treatment of the membranes with diisopropyl phosphorofluoridate (DFP), an irreversible inhibitor which is free soluble in lipid, produced an almost complete inactivation of AChE. The inhibition was prevented in assays performed with the non-permeant reversible inhibitor BW 284c51 (BW). (4) Similar results were obtained if echothiophate iodide (ECHO), an irreversible and poorly permeant inhibitor, instead of DFP was used. (5) Sedimentation profiles of enzyme solubilized with Triton X-100 from membranes inhibited by DFP after protection with BW showed a minor reduction in the relative proportion of a 4.5 S (G1) form. (6) Treatment of intact or saponin-permeabilized membranes with concanavalin A (ConA) produced enzyme-lectin complexes. In both cases, most of the enzyme was recovered in the sedimented complexes after centrifugation of the Triton-solubilized membranes. (7) Incubation of intact membranes with the antibody AE1 led to the formation of immuno complexes. Sedimentation analyses of the molecular forms of AChE revealed a shift in the sedimentation coefficients, whether the antibody was added before or after solubilization of the enzyme. (8) These results firmly establish an external localization of AChE in SR, most of the protein backbone facing the cytoplasmic side of the membrane.
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PMID:Acetylcholinesterase is orientated facing the cytoplasmic side in membranes derived from sarcoplasmic reticulum. 199 25

Primary cultures of avian muscle cells express both globular and asymmetric molecular forms of acetylcholinesterase (AChE) when grown in a simple defined culture medium. Under these conditions, we analyzed the role of various agents interfering with muscular activity: tetrodotoxin (TTX) and veratridine, as well as a depolarizing concentration of KCl. These treatments caused the complete cessation of contractions in mature myotubes. We observed no influence on cellular AChE activity. The paralyzing treatments induced different effects on AChE secretion: TTX increased the secretion by approximately 25%, whereas KCl and veratridine reduced it by approximately 30%. The proportions of secreted molecular forms (mostly hydrophilic G4 and G2) were not modified significantly. TTX did not affect the pattern of molecular forms of cellular AChE (in particular, the proportion of A forms was not changed). Depolarization by veratridine or KCl induced an increase in the proportion of A forms in mature myotubes by a factor of 2-3. Similar results were obtained with quail myotubes cultured under the same conditions. This study shows that, in avian muscle cultures, the ionic balance across myotube membranes, rather than muscular activity per se, can regulate the level of A forms and the rate of AChE secretion. These results do not exclude the possible involvement of other factors, such as Ca2+ and/or peptidic factors. In addition, taking together our results and data from the literature. we conclude that the expression of AChE molecular forms depends both on the species and on the culture conditions used.
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PMID:Regulation of the expression of acetylcholinesterase by muscular activity in avian primary cultures. 201 53

In order to investigate whether a fibrin-fibronectin-containing matrix of a peripheral regeneration chamber could promote the growth of central nervous system neurons, hippocampal and septal slices were co-cultured in the presence of this acellular substrate. In introducing the peripheral matrix into a 2-mm-long tube between hippocampal and septal slices, a spatio-temporal sequence of cell migration and axonal growth was described by light and electron microscopy. Axons were able to elongate directly into the flocculent material constituting the matrix and a possible neurite-promoting activity was implicated in this process as axonal growth was not detected in direct contact with rat plasma coagulated with calcium, or chicken plasma coagulated with thrombin, used as control matrices. However, in the 3 different substrates tested, astrocytes were able to migrate and dilated astroglial processes containing intermediate filaments were detected. Axonal processes were observed growing on the glial cell surface. GFAP-positive phagocytic cells, that could be of the same origin as astrocytes, were involved in matrix removing. Neuronal growth and glial migration arose from hippocampal and septum slices and acetylcholinesterase-containing fibers were seen in the bridging structure suggesting that cholinergic axons were able to progress to the hippocampal slice. This technique appeared to provide a model in which axonal growth and cell migration can be studied 'in vitro' in a 3-dimensional environment.
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PMID:Axonal growth and glial migration from co-cultured hippocampal and septal slices into fibrin-fibronectin-containing matrix of peripheral regeneration chambers: a light and electron microscope study. 205 10

The effects of oxotremorine, arecoline and muscarine on neuromuscular transmission of mouse or rat phrenic nerve-diaphragm were investigated. For some studies of endplate potentials (e.p.p.s) the preparation was immobilized by cutting muscle fibers. Oxotremorine (0.3-10 microM) depolarized endplate membranes, reduced miniature e.p.p. amplitudes but increased frequency, induced spontaneous neural discharges and muscle fasciculations, and produced contracture of denervated mouse diaphragm. In mouse and young rat preparations pretreated with Mn2+, Co2+, Ni2+, Cd2+ or low Ca2+ Tyrode to depress evoked acetylcholine release, oxotremorine 0.3-1 microM increased indirect twitches as well as amplitudes and quantal contents of e.p.p.s. These increases were not observed when the synaptic transmission was not depressed, nor in adult rat preparations. The augmentation by oxotremorine of evoked acetylcholine release persisted in preparations pretreated with neostigmine (1 microM) and tetrodotoxin (20 nM), which inhibited acetylcholinesterase and oxotremorine-induced spontaneous neural discharges. These effects of oxotremorine were mimicked by arecoline but not by muscarine and were antagonized by tubocurarine (0.3 microM) but not by atropine (0.1-10 microM). Atropine alone did not affect indirect twitches, synaptic transmission, tetanic responses evoked by direct stimulation of diaphragms, nor the durations of muscle action potential. The direct twitch responses were only slightly increased by oxotremorine at 2-3 microM. Oxotremorine at high concentrations (greater than 2 microM), depressed indirect twitches and e.p.p. amplitude, and accelerated the run-down of trains of e.p.p.s. The IC50 on indirect twitches was reduced by pretreatment with diltiazem or proadifen, which are known to promote receptor desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nicotinic actions of oxotremorine on murine skeletal muscle. Evidence against muscarinic modulation of acetylcholine release. 207 79

In primary cell cultures of rat superior cervical ganglia (SCG) the tailed asymmetric 16S molecular form of acetylcholinesterase (AChE) possesses hydrophilic (high-salt soluble, HSS) and hydrophobic (detergent extracted, DE) variants. Hydrophobic tailed acetylcholinesterase is associated with membranes through a glycolipid anchor. In the presence of tunicamycin, an antibiotic which inhibits protein glycosylation, the cellular amount of the hydrophobic DE 16S AChE is increased. Exposure of the cells to the calcium ionophore A 23187 leads to a decrease in DE 16S AChE and a correlated increase in hydrophilic HSS 16S AChE. These results suggest the existence of an endogenous processing of tailed AChE, transforming the hydrophobic variant into an hydrophilic one controlled through glycosylation and intracellular calcium.
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PMID:Cell modulation of hydrophobic tailed 16S acetylcholinesterase by intracellular calcium in rat superior cervical ganglion neurons. 209 23


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