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)

Prolonged acrylamide administration produces motor nerve-terminal branch degeneration and impairs axonal outgrowth following nerve crush. It is unclear how early terminal branch degeneration is initiated and whether there is a compensatory regenerative response at the neuromuscular junction (NMJ). A modified Pestronk and Drachman silver-acetylcholinesterase strain was used to carry out a detailed morphometric analysis of the NMJ in soleus and lumbrical muscles. Rats were given 3, 5, or 10 doses of acrylamide, 35 mg/kg/day, by intraperitoneal injection, 5 days/week, and killed 4, 7, or 14 days after the first dose, respectively. Degenerating terminal branches were evident in soleus NMJ after only three doses of acrylamide. Diminished synaptic vesicle content, neurofilament accumulations and tubulo-vesicular profiles were evident after three doses. At later time points, degenerating terminals contained few synaptic vesicles and were engorged with neurofilaments. Endplate lengthening, indicative of denervation supersensitivity, accompanied degeneration. Terminal sprouting proliferated after 3 and 5 doses but was less prominent after 10 doses. Although similar changes occurred in the lumbrical muscle, they were not initiated until after 5 doses. These experiments reveal that pathological changes in terminal branches commence earlier and after a lower cumulative dose of acrylamide than previously reported and suggest that acrylamide exerts a primary effect at motor nerve-terminal branches. Early, vigorous terminal sprouting indicates that acrylamide does not prevent the initiation of regeneration, but with prolonged treatment does cause degeneration of maturing sprouts.
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PMID:Early degeneration and sprouting at the rat neuromuscular junction following acrylamide administration. 240 31

The possible involvement of calmodulin in mediating the calcium requirement for retrograde axonal transport of acetylcholinesterase was studied in vitro in bullfrog spinal nerves, with the use of the calmodulin inhibitors amitriptyline and desipramine. When nerves were preincubated with 0.2 mM amitriptyline or desipramine for 5 h, and were then ligated and incubated for an additional 17-18 h in drug-containing medium, the accumulation of acetylcholinesterase distal to the ligature was significantly reduced as compared to contralateral control nerves maintained in drug-free medium. The identical degree of transport inhibition observed for both drugs is consistent with their similar anti-calmodulin activity.
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PMID:Inhibition of the retrograde axonal transport of acetylcholinesterase by the anti-calmodulin agents amitriptyline and desipramine. 240 26

In the peripheral nerves of birds and mammals, acetylcholinesterase (AChE) exists in four main molecular forms (G1, G2, G4, and A12). The two heaviest forms (G4 and A12) are carried by rapid axoplasmic transport, whereas the two lightest forms (G1 and G2) are probably much more slowly transported. Here we report that nerves innervating fast-twitch (F nerves) and slow-twitch (S nerves) muscles of the rabbit differ both in their AChE molecular form patterns and in their anterograde and retrograde axonal transport parameters. Since we had previously shown a selective regulation of this enzyme in fast and slow parts of rabbit semimembranosus muscle, we wondered whether the differences observed in the nerve could be affected by the twitch properties of muscle. The results reported here show that in F nerves that reinnervate slow-twitch muscles, both the AChE molecular form patterns and axonal transport parameters turn into those of the S nerve. These data suggest the existence of a retrograde specific effect exerted by the muscles on their respective motoneurons.
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PMID:Retrograde effect of muscle on forms of acetylcholinesterase in peripheral nerves. 241 67

A cholinotoxin, ethylcholine mustard aziridinium ion, (AF64A) specifically and irreversibly blocks the intraaxonal transport of acetylcholinesterase in the rat. Impairment of the transport of this enzyme in the septo-hippocampal cholinergic fibres and in the sciatic nerve has been studied, using different doses of AF64A. It is demonstrated that the effect on the axonal transport is dose-dependent, but is not related to the mode of drug application. AF64A thus may exert its neurotoxic effects on cholinergic neurons at several target sites of action. In addition to the localized presynaptic mechanisms, it may also be compromising cholinergic function by inhibiting axonal transport in vivo.
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PMID:Ethylcholine mustard aziridinium blocks the axoplasmic transport of acetylcholinesterase in cholinergic nerve fibres of the rat. 241 97

The anterograde and retrograde axonal flow of acetylcholinesterase were studied in the sciatic nerve of alloxan-diabetic rats after five weeks of experimental diabetes. A slight reduction of the anterograde axonal flow of the enzyme was found in alloxan-diabetic compared to control rats. Sedimentation analysis revealed a major reduction of anterograde axonal flow of the light globular forms of the enzyme (G1 + G2), which are probably conveyed by slow transport. There was also a minor reduction of the anterograde flow of the globular form G4, while no modification of the axonal flow of the heavy asymmetric form A12 was found. Both G4 and A12 molecular forms are conveyed by fast axonal transport. In contrast, no abnormality of the retrograde axonal flow of acetylcholinesterase was observed. Ganglioside treatment antagonized the decline of the anterograde axonal flow of the enzyme in alloxan-diabetic rats. These results are consistent with the view that experimental diabetic neuropathy is associated with axonal transport defects, and suggest a protective effect of ganglioside treatment against neuronal damage(s) related to the diabetic syndrome.
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PMID:Impaired axonal transport of acetylcholinesterase in the sciatic nerve of alloxan-diabetic rats: effect of ganglioside treatment. 242 5

In this study, we examined 26 cases of Alzheimer's disease (AD) and 14 age-matched controls. In Brodmann area 21 cerebral cortex of the AD cases, there was no change in soluble G1 and G4 acetylcholinesterase (AChE) (EC 3.1.1.7), a significant 40% decrease in membrane-associated G4 AChE, significant 342 and 406% increases in A12 and A8 AChE, and a significant 71% decrease in choline acetyltransferase (ChAT) (EC 2.3.1.6). Our working hypothesis to account for these changes postulates that soluble globular forms are unchanged because they are primarily associated with intrinsic cortical neurons that are relatively unaffected by AD, that ChAT and membrane-associated G4 AChE decrease because they are primarily associated with incoming axons of cholinergic neurons that are abnormal in AD, and that asymmetric forms of AChE increase because of an acrylamide-type impairment of fast axonal transport in diseased incoming cholinergic axons. In the nucleus basalis of Meynert (nbM) of the 26 AD cases, there was a significant 61% decrease in the number of cholinergic neurons, an insignificant 23% decrease in nbM ChAT, a significant 298% increase in nbM ChAT per cholinergic neuron, and a significant 7% increase in the area of cholinergic perikarya. To account for the increased ChAT in cholinergic neurons and the enlargement of cholinergic perikarya, we propose that slow axonal transport may be impaired in nbM cholinergic neurons in AD.
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PMID:Molecular forms of acetylcholinesterases in Alzheimer's disease. 243 Aug 39

The effects of the calmodulin inhibitors amitriptyline, desipramine, imipramine, and clomipramine on fast axonal transport, oxidative metabolism, and density of axonal microtubules were measured in bullfrog spinal nerves in vitro. The four drugs tested inhibited the fast orthograde transport of [3H]leucine-labelled proteins and the fast retrograde transport of acetylcholinesterase at a concentration of 0.2 mM. Amitriptyline, desipramine, and imipramine were equipotent inhibitors of transport, and clomipramine was a more potent inhibitor than imipramine. The adenosine triphosphate content of the nerves was reduced by at most 19% by the compounds under study; such a reduction cannot account for the inhibition of fast axonal transport. Desipramine and imipramine had no significant effect on the density of microtubules in unmyelinated axons, whereas amitriptyline only reduced it by 18%; the inhibition of axonal transport by these three drugs can therefore not be explained by microtubule disruption. Clomipramine reduced microtubular density by 40%, and this effect may have contributed to the inhibition of fast axonal transport. The inhibition of fast axonal transport by desipramine, imipramine, and amitriptyline may be related to the inhibition of calmodulin function by these drugs. The similar potency of these three drugs as inhibitors of fast axonal transport goes in parallel with their known similar potency as calmodulin antagonists.
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PMID:Inhibition of fast axonal transport in bullfrog nerves by dibenzazepine and dibenzocycloheptadiene calmodulin inhibitors. 243 70

Previous morphological studies of the adult rat soleus neuromuscular junction (NMJ) indicate that its ultrastructure changes with age, a consequence of a dynamic, ongoing remodeling of pre- and postsynaptic elements. With aging, the balance between axonal sprouting and withdrawal appears to shift in favor of denervation. Here we have examined the extent and direction of the remodeling process during the adult life of the rat (5-111 weeks) by quantification and morphometry of NMJ structure as seen in electron microscopic composites and in cholinesterase (ChE) stained whole mounts. We have found that the net effect of axonal sprouting and withdrawal on the entire NMJ region varies with age: at 5-12 weeks there is rapid growth and maturation; at 12-48 weeks slower growth occurs, and at 48-82 weeks there is a gradual shift in direction to result in progressive loss of synaptic contact in individual NMJs; finally, at 82-111 weeks, there is loss of entire NMJs with some continued reinnervation at others. The diaphragm NMJ also exhibits continuous structural remodeling; however, between 82-111 weeks many changes in the ChE staining pattern appear abruptly.
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PMID:Aging rat neuromuscular junctions: a morphometric study of cholinesterase-stained whole mounts and ultrastructure. 243 45

The effects of increases in neuronal activity on fast axonal transport of acetylcholinesterase (AChE) in sciatic motoneurons were studied by subjecting rats to daily running or swimming training (8 weeks). Net accumulation of AChE activity proximal and distal to a ligature served to evaluate orthograde and retrograde transport. Results showed that runners had greater orthograde and retrograde transport of AChE as compared to control animals, while no changes were found in swimmers. These adaptations in the runners were caused by the long-term nature of the training regimen since an acute exercise session had no effect on AChE transport. The observed changes may be attributed to an increase in the mobile fraction of AChE in the motoneurons. Since swimming training had no effect on transport but entails a high level of neuronal activity, it is suggested that increased impulse activity is not the factor mediating the adaptations in axonal transport of AChE which resulted from running training.
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PMID:Fast axonal transport of acetylcholinesterase in rat sciatic motoneurons is enhanced following prolonged daily running, but not following swimming. 244 73

The enzyme specificity of the Karnovsky staining was examined. Tetraisopropylpyrophosphoramide made the staining difference between anterior and posterior roots clearer. Rat sciatic nerve, gluteal muscle branch and sural nerve were ligated and retrograde changes were examined histologically and histochemically. In ligated sciatic nerve, axonal degeneration similar to Wallerian degeneration occurred within 5 mm proximal to ligation while acetylcholinesterase activity decreased in more proximal portions. Sections of ligated gluteal muscle branch showed marked increase of small myelinated fibers 6 weeks after ligation and the mean cross sectional area of myelinated fibers decreased due to the new small fibers. The mean cross sectional area of myelinated axons also decreased in ligated sural nerve but myelinated fibers did not so remarkably increase in number as ligated gluteal muscle branches. Histochemical funicular orientation could be reliable if performed soon after nerve injury before retrograde changes spread in the proximal stump.
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PMID:[Histochemical study of retrograde degeneration in ligated peripheral nerves]. 244 11


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