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)

p-(trimethyl ammonium) benzene diazonium difluoroborate (TDF), an affinity-labeling reagent of the acetylcholine receptor site(s), which in the normal cell acts as an irreversible inhibitor becomes a reversible activator after in vivo exposure of the electroplax to dithiothreitol (DTT), a disulfide bond reducing agent. After in vitro exposure of acetylcholinesterase to DTT, TDF becomes a reversible competitive inhibitor of the enzyme, using indophenyl acetate as the substrate. Both acetylcholinesterase and the macromolecular receptor of acetylcholine thus contain disulfide bonds. Additional experiments with DTT suggest that there might exist several different classes of receptor sites for cholinergic agents in the excitable membrane of the electroplax.
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PMID:Compared effects of dithiotreitol on the interaction of an affinity-labeling reagent with acetylcholinesterase and the excitable membrane of the electroplax. 526 Sep 26

An equilibrium dialysis technique, applied to lyophilized particulate fractions of Torpedo electroplax, gave data consistent with a single kind of macromolecular binding of muscarone, with binding constant, 7 x 10(-7)M and an amount of 1 nmole per gram original electroplax. The effects on muscarone binding of 38 drugs suggested that muscarone binding reflected acetylcholine receptor activity. Of 18 enzyme preparations, only trypsin, chymotrypsin, and phospholipase C reduced binding activity, suggesting that a phospholipoprotein was binding. Partial "solubilization" of the binding protein was achieved, but the "solubilized" activity did not migrate on electrophoresis. Additional evidence was provided that acetylcholinesterase was not responsible for this muscarone binding.
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PMID:A muscarone-binding material in electroplax and its relation to the acetylcholine receptor. II. Dialysis assay. 526 75

A term infant required intubation for respiratory depression. Examination revealed hypotonia and areflexia with intact extraocular movements. Electrodiagnostic studies demonstrated defective neuromuscular transmission characterized by borderline low motor evoked amplitudes, profound decremental responses at all stimulation rates, and moderate facilitation (50 to 740%) 15 seconds after 5 seconds of 50 Hz stimulation. Repetitive muscle action potential responses were not recorded following stimulation of nerves by single shocks. Sensory evoked responses and needle electromyographic findings were normal, as were acetylcholine receptor antibody levels. Results of muscle histochemical analyses, including acetylcholinesterase stains, were normal. End-plate histometric analyses demonstrated only a slight reduction in mean synaptic vesicle diameter compared with that in an adult control subject. In vitro muscle contractile properties, stimulating the muscle directly, were normal. Anticholinesterase medications were ineffective. Guanidine produced clinical deterioration. The amplitude of motor evoked responses progressively declined, whereas the percentage of decrement and amount of post-tetanic facilitation increased. Although the nature of the transmission defect was not identified, the data are consistent with abnormal acetylcholine resynthesis, mobilization, or storage without abnormality of release or receptors.
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PMID:Abnormal neuromuscular transmission in an infantile myasthenic syndrome. 608 19

Coexistence of neurotransmitter-synthesizing enzymes choline acetyltransferase, cysteine sulfinic acid decarboxylase, tyrosine hydroxylase, and L-glutamic acid decarboxylase was demonstrated at human and primate neuromuscular junctions with specific antibodies directed against these enzymes. Motor end plates were identified in unfixed cryostat sections by standard cholinergic markers for acetylcholinesterase and the acetylcholine receptor. Each of the four transmitter-synthesizing enzymes was localized at end plates displaying these markers. The presence of any two of the four enzymes at a given end plate was established by (i) showing immunoreaction for one enzyme followed by elution and demonstration of immunoreaction for a second enzyme, and (ii) paired immunofluorescence with simultaneous demonstration of one enzyme with a rhodamine-labeled second antibody and of the other enzyme with a fluorescein-labeled second antibody. These findings imply that motor nerve terminals have the capacity for synthesizing not only acetylcholine but also taurine, catecholamines, and gamma-aminobutyric acid. These substances, in turn, may participate in the normal regulation of nerve-muscle interaction or be significant in specific disorders involving the motor unit.
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PMID:Coexistence in human and primate neuromuscular junctions of enzymes synthesizing acetylcholine, catecholamine, taurine, and gamma-aminobutyric acid. 612 24

Acetylcholine receptor appearance rate in the presence of the phenothiazines trifluoperazine and chlorpromazine was measured in cultured embryonic chick myotubes by means of 125I-alpha-bungarotoxin. At drug concentrations of 5 to 10 X 10(-6) M, receptor appearance rate was significantly enhanced while receptor half-life, cellular protein, net protein synthesis rate, and acetylcholinesterase levels were not similarly affected. The sulfoxide derivatives were without effect. At concentrations of 3 X 10(-5) M and above, both trifluoperazine and chlorpromazine caused myotube contracture and cell loss. Drug combination experiments revealed that receptor stimulation caused by phenothiazines is overcome by low concentrations of veratridine and ryanodine, but not by membrane depolarization with 20 mM KCl. These results lend support to the role of calcium as an intracellular messenger in acetylcholine receptor synthesis regulation, but are difficult to reconcile with the notion that cytosolic calmodulin serves as the calcium receptor in this signaling pathway. Since the trifluoperazine effect resembles that caused by the calcium antagonist D-600, phenothiazines may stimulate receptor synthesis by blocking a voltage-gated calcium channel.
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PMID:Trifluoperazine stimulates acetylcholine receptor synthesis in cultured chick myotubes. 614 23

Actinomycin D (ACT-D), an inhibitor of transcription, was added to chick muscle cultures to study its effect on the synthesis of acetylcholine receptor (ACHR) and acetylcholinesterase (ACHE, EC 3.1.1.7). Doses of ACT-D (1.85-18.5 nM), which inhibited uridine incorporation up to 80%, increased ACHR, ACHE, and creatine kinase (CK, EC 2.7.3.2) levels without affecting general cell protein. Degradation of ACHR was slower in ACT-D treated cultures than controls, resulting in a twofold increase in receptor half-life. Uridine incorporation was inhibited by ACT-D in both mononucleated cells and myotubes and [3H]uridine nuclear grain distribution were shifted to values lower than controls. The results indicate that posttranscriptional effects of ACT-D increase levels of ACHR, ACHE, and CK and that decreased degradation could account for the increase in the number of surface ACH receptors.
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PMID:Alteration of acetylcholine receptor and acetylcholinesterase metabolism by actinomycin D in cultured muscle cells. 617 Apr 4

The appearance of acetylcholinesterase (AChE) at newly formed nerve-muscle synapses depends on synaptic transmission. Synapses form when cultures are grown in the presence of acetylcholine receptor antagonists, but AChE does not accumulate at these synapses. The important component of transmission seems to be muscle activity. Treatment with dibutyryl cyclic GMP mimics muscle activity, directly inducing synaptic AChE appearance.
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PMID:Regulation of acetylcholinesterase appearance at neuromuscular junctions in vitro. 624 95

The acetylcholine receptor is a protein that contains certain critical disulfide bonds. Experiments were designed to determine the role such bonds might play in the physiological activity of the receptor. Modification of the receptor with sodium bisulfite and diamide produced an increase in the time constants of the miniature endplate current without changes in the single-channel properties of the receptor. Controls were done to determine that this change in the miniature endplate current was not due to an effect on acetylcholinesterase at the endplate. These data are interpreted to mean that the reagents increase the time acetylcholine is bound to the receptor before the channel opens and is most probably due to a change in receptor affinity brought about by chemical modification of the receptor protein.
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PMID:Changes in neuromuscular junction endplate current time constants produced by sulfhydryl reagents. 627 90

1. Basic features of the elementary bioelectric signals such as miniature-endplate-potentials are molecularly interpreted on the basis of relaxation kinetic data of isolated acetylcholine receptor and acetylcholinesterase. Electrophysiological and molecular data suggest an essentially sequential processing of acetylcholine by receptor and esterase. 2. Flux measurements with sealed biomembrane fragments containing acetylcholine receptor show that the ion-transporting conformation of the receptor-channel is a short-lived metastable state. In the presence of neuroactivators the receptors inactivate. The description of the flux-inactivation requires a cyclic reaction scheme similar to the desensitization scheme of KATZ and THESLEFF (1957). 3. The recently introduced concept of integrated flux rate coefficients permits us to derive gating mechanisms from flux data under well-defined experimental conditions: sealed biomembrane vesicles, activator concentration, type of transported ion. 4. With respect to activation and inactivation and the metastability of the ion-conducting conformation, there are fundamental similarities between the axonal Na+ ion channel and the acetylcholine receptor-channel.
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PMID:Ion flow gating by the acetylcholine system: kinetics of isolated receptor and esterase and of receptor-mediated ion flux. 628 56

Five familial cases (in two families) and one sporadic case of a new congenital myasthenic syndrome were investigated. Symptoms arise in infancy or later life. Typically, one finds selective involvement of cervical, scapular, and finger extensor muscles, ophthalmoparesis, and variable involvement of other muscles. There is a repetitive muscle action potential to single nerve stimulus in all muscles and a decremental response at 2 to 3 Hz stimulation in clinical affected muscles. Microelectrode studies reveal markedly prolonged end-plate potential (epp), miniature end-plate potential (mepp), and miniature end-plate current; normal quantum content of the epp; and a smaller than normal or low-normal mepp amplitude. Light microscopy demonstrates predominance of type I fibers, small groups of atrophic fibers, tubular aggregates and vacuoles near end-plates, abnormal end-plate configuration, and nonspecific myopathic changes. Abundant acetylcholinesterase activity is present at all end-plates, and the activity and kinetic properties of this enzyme in muscle are normal. Calcium accumulated at the end-plate in one patient. Quantitative electron microscopy shows decrease in the size of nerve terminals, increase in the density of synaptic vesicles, and reduction in the length of postsynaptic membranes. There is focal degeneration of junctional folds with corresponding loss of acetylcholine receptor, most marked in cases with the lowest mepp amplitude. There are no immune complexes at the end-plate. Fiber regions near end-plates display dilation, proliferation, and degeneration of the sarcoplasmic reticulum; nuclear, mitochondrial, and myofibrillar degeneration; and vacuoles resembling those found in periodic paralysis. A prolonged open time of the acetylcholine-induced ion channel is considered to be the basic abnormality and may account for the physiological, morphological, and clinical alterations.
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PMID:A newly recognized congenital myasthenic syndrome attributed to a prolonged open time of the acetylcholine-induced ion channel. 628 11


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