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)

By the mid-1970s the autoimmune origin of myasthenia gravis had been well established. Once this feat had been accomplished, it also became apparent that myasthenic disorders occurring in a genetic or congenital setting had a different etiology. As a result, a number of distinct myasthenic syndromes have been recognized and investigated by electrophysiological and ultrastructural methods. The newly recognized disorders are conditioned by divergent causes, such as a failure of acetylcholine resynthesis or packaging, absence of acetylcholinesterase from the neuromuscular junction, abnormal gating properties of the acetylcholine receptor-associated ion channel, or an abnormality in the regulation of the density of acetylcholine receptor molecules in the postsynaptic membrane. These genetic defects either impair neuromuscular transmission directly or result in secondary derangements that eventually compromise the safety margin of neuromuscular transmission.
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PMID:Congenital myasthenic syndromes. 305 79

The role of the calcium ion Ca2+ as an agent of intracellular control in a variety of physiological processes is well established. In vertebrate skeletal muscle fibers, Ca2+ is involved in muscle contraction, modulation of membrane permeability and regulation of metabolic activity. Recently it was suggested that ion fluxes through membranes regulate the level of two cholinergic macromolecules, the acetylcholine receptor and the A12 form of acetylcholinesterase (AChE), the presumed synaptic form of the enzyme. Muscle cells paralysed by veratridine, which maintains the Na+ channel in the open state, showed an increase in total AChE and in the levels of the A12 form. The effect of veratridine on AChE was blocked in the presence of agents that block Ca2+ permeability suggesting that Ca2+ is involved in this effect. To understand whether the level of muscle AChE is related in some way to the level of free intracellular Ca2+, we analysed the variations of Ca2+ levels in rat muscle cells treated by agents which modify the ionic permeabilities. This level was determined by spectrofluorimetry using the fluorescent Ca2+ indicator: Quin 2. However no correlation between these parameters was observed in our experimental conditions.
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PMID:[Is muscular acetylcholinesterase activity correlated with the intracellular concentration of free calcium?]. 314 91

It was previously reported that the acetylcholine receptor clusters and acetylcholinesterase appear on embryonic superior oblique muscle cells developing in vivo without motor nerve contacts. The objective of this study was to examine whether some other components of neuromuscular junction also form on muscle cells developing in vivo in the absence of motor neurons. In the present study, postsynaptic specializations such as junctional folds, postsynaptic density and basal lamina were studied in normal and aneural muscles. The superior oblique muscle of duck embryos was made aneural by permanent destruction of trochlear motor neurons by cauterizing midbrain on embryonic day 7; 3 days before the motor neurons normally project their axons into the muscle. Normal and aneural muscles from embryonic days 10 to 25 were processed for electron microscopy. The results indicate that morphological specializations such as junction-like folds, postsynaptic-like density, and basal lamina also develop in the absence of motor neuron contacts. Whether the differentiation of specialized synaptic basal lamina is dependent on the presence of motor neurons was examined by utilizing a monoclonal antibody against heparan sulfate proteoglycan. Immunohistochemical studies indicate that specialized synaptic basal lamina differentiates in the absence of motor neurons. Thus, the mechanism of development of postsynaptic components of neuromuscular junction in this muscle is not dependent on motor neuron contacts. These results also suggest that the postsynaptic cell plays a more active role in synapse formation than previously realized. The results are discussed in relation to the control of synapse numbers by the postsynaptic cell.
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PMID:Development of postsynaptic-like specializations of the neuromuscular synapse in the absence of motor nerve. 322 92

Motor nerve terminal outgrowth (NTO) at neuromuscular junctions (NMJs) occurs rapidly in response to denervation changes in muscle. We have previously found that NTO can produce an elongation of the synaptic area of the NMJ as defined by cholinesterase-silver staining. In the present study, we examined the effects of NTO on a postsynaptic muscle membrane component, the usually stable cluster of acetylcholine receptors (AChRs) at the NMJ. NTO was evoked in rat soleus muscles using botulinum toxin. AChRs were demonstrated using immunocytochemistry or autoradiography of alpha-bungarotoxin binding. Our results show that NTO induces rapid elongation of the cluster of AChRs at the NMJ within 7 d of treatment with botulinum toxin. The growth in the size of the AChR clusters was accompanied by an increase in the number of AChRs/NMJ. No elongation of AChR clusters was seen following surgical denervation, suggesting that cluster growth is related to NTO and not to denervation changes in muscle per se. Growth of NMJ-AChR clusters appeared to result primarily from 2 processes: insertion of new AChRs into the NMJ membrane and, surprisingly, redistribution of preexisting NMJ-AChRs. These results show that NTO can cause rapid changes in the normally stable cluster of AChRs at the NMJ. Motor nerve terminals provide a strong and anatomically precise control of AChRs at the NMJ.
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PMID:Mechanisms of postsynaptic plasticity: remodeling of the junctional acetylcholine receptor cluster induced by motor nerve terminal outgrowth. 330 23

The formation of acetylcholine receptor (AChR) clusters can be induced by basic polypeptide-coated latex beads in cultured Xenopus muscle cells. Here we investigated the development of acetylcholinesterase (AChE) at the bead-induced AChR clusters. AChE activity began to appear at the clusters after 1 day of bead-muscle coculture and was present at all of the bead-induced clusters within 4-7 days. Electron microscopy revealed that AChE reaction products were discretely localized within the cleft and the membrane invaginations at the bead-muscle contacts. Thus, the beads can mimic the nerve in inducing a local accumulation of both the AChRs and AChE, suggesting that the development of both specializations can be effected by a common stimulus.
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PMID:Development of acetylcholinesterase induced by basic polypeptide-coated latex beads in cultured Xenopus muscle cells. 337 75

In adult vertebrate striated muscle, the nicotinic acetylcholine receptor (AChR) is almost exclusively localized in the postsynaptic membrane of the neuromuscular junction. Using in situ hybridization, we show that, in two different chicken muscles [the slow multi-innervated anterior latissimus dorsi (ALD) and the fast singly innervated posterior latissimus dorsi (PLD)], the AChR alpha-subunit mRNA is detected at discrete regions on myofibres and that these regions co-localize (80% correspondence) with neuromuscular junctions identified by histochemical staining for acetylcholinesterase. Moreover, autoradiographic grains densely accumulate on and around subsynaptic nuclei. In contrast, hybridization with an actin probe results in a strong signal distributed over the entire length of the myofibres. Denervation increases the level of AChR alpha-subunit mRNA both in the PLD and to a lesser extent in the ALD. By in situ hybridization we observe that, although a perinuclear pattern is maintained, the labelled nuclei appear randomly distributed among approximately 10% of the nuclei. These results are discussed in a model of AChR gene expression in vertebrate striated muscle fibres.
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PMID:Detection of the nicotinic acetylcholine receptor alpha-subunit mRNA by in situ hybridization at neuromuscular junctions of 15-day-old chick striated muscles. 339 33

After denervation in vivo, the frog cutaneus pectoris muscle can be led to degenerate by sectioning the muscle fibers on both sides of the region rich in motor endplate, leaving, 2 wk later, a muscle bridge containing the basal lamina (BL) sheaths of the muscle fibers (28). This preparation still contains various tissue remnants and some acetylcholine receptor-containing membranes. A further mild extraction by Triton X-100, a nonionic detergent, gives a pure BL sheath preparation, devoid of acetylcholine receptors. At the electron microscope level, this latter preparation is essentially composed of the muscle BL with no attached plasmic membrane and cellular component originating from Schwann cells or macrophages. Acetylcholinesterase is still present in high amounts in this BL sheath preparation. In both preparations, five major molecular forms (18, 14, 11, 6, and 3.5 S) can be identified that have either an asymmetric or a globular character. Their relative amount is found to be very similar in the BL and in the motor endplate-rich region of control muscle. Thus, observations show that all acetylcholinesterase forms can be accumulated in frog muscle BL.
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PMID:Globular and asymmetric acetylcholinesterase in frog muscle basal lamina sheaths. 348 6

In the frog nerve, 3H-bungarotoxin and 3H-acetylcholine binding increased whereas the acetylcholinesterase activity decreased in rhythmic stimulation. The enhancement of 3H-bungarotoxin binding to nerve during the rhythmic stimulation seems to stem from transformation of "inactive" forms of acetylcholine receptor of glial membrane to "active" ones.
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PMID:[Binding of 3H-bungarotoxin by nerve trunks of the frog during excitatory conduction]. 348 69

Rats treated intravenously with an organophosphorus anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7 sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucose as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8 LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2 hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50% in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.
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PMID:Cerebral metabolic effects of organophosphorus anticholinesterase compounds. 350 39

Numerous studies have shown that the acetylcholine receptor (AChR) is inserted in the plasma membrane of the muscle fiber, and that it is focalized at the site of neuromuscular junctions, as an effect of neural influence. In contrast, acetylcholinesterase (AChE) may be presynaptic or anchored in the basal lamina, as well as postsynaptic at neuromuscular junctions. We investigated the origin of the junctional enzyme, particularly the collagen-tailed asymmetric A12 forms, by studying the AChE contents of heterologous rat and chicken neuromuscular cocultures by immunohistochemical and biochemical methods. We found that the overall content of AChE, in the neuromuscular cocultures, including the A12 form, was essentially identical to the sum of the contents of separate myotube and motoneuron cultures. The sedimentation coefficients of the rat and chicken asymmetric forms are sufficiently different to clearly differentiate these enzymes in sucrose gradients: 16 S for rat, 20 S for chicken A12 AChE. Sedimentation analyses of AChE in cocultures thus showed that the A12 form was of muscular origin. In the case of aneural cultures of myotubes, histochemical staining of AChE activity or immunohistochemical staining with specific antibodies showed only very scarce, faint concentrations of enzyme. Some patches of acetylcholine receptor (AChR) were, however, visible in these cultures. Neuromuscular contacts are readily established in cocultures of myotubes with embryonic motoneurons from spinal cords. In the presence of motoneurons, the myotubes presented a larger number of AChR patches. The most remarkable feature of neuromuscular cocultures was the presence of numerous intense AChE patches which always coincided with AChR clusters. By specifically staining nerve terminals with tetanus toxin, we could show an excellent correlation between neuromuscular contacts and the presence of AChE-AChR patches. We found that the AChE patches in heterologous cocultures could be stained exclusively by the anti-myotube AChE antiserum. The focalized enzyme is therefore exclusively, or very predominantly, provided by the myotube.
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PMID:Presynaptic or postsynaptic origin of acetylcholinesterase at neuromuscular junctions? An immunological study in heterologous nerve-muscle cultures. 352 79


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