Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 37-year-old man suffered from photosensitivity and urinary casts with serological findings of positive anti-DNA antibody, LE cells and false positive VD reaction in September of 1979. He developed general fatigue, dyspnea and diplopia with ptosis of bilateral eyelids in November of 1979, which were improved by the anti-cholinesterase drugs. In January of 1980, he had an attack of unconsciousness and his chest X-ray film showed several tumorous shadows in the anterior mediastinum and middle and lower lung fields. Treating him with chemotherapy of VEMP, the pulmonary shadows disappeared. However, he developed severe muscle weakness with an elevated CPK (430 mU/ml) and a myogenic EMG pattern along with an increased anti-acetylcholine receptor antibody (243 n Mol/l), dysphagia and eyelid-ptosis. He died in September of 1985 and his autopsy disclosed a malignant thymoma of mixed type in the anterior mediastinum and an atrophy and fibrosis with infiltration of inflammatory cells in the striated muscles.
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PMID:[An autopsy case of a patient with myasthenia gravis who showed various symptoms of collagen diseases and complicated with malignant thymoma]. 281 7

Several lines of evidence have led to the hypothesis that agrin, a protein extracted from the electric organ of Torpedo, is similar to the molecules in the synaptic cleft basal lamina at the neuromuscular junction that direct the formation of acetylcholine receptor and acetylcholinesterase aggregates on regenerating myofibers. One such finding is that monoclonal antibodies against agrin stain molecules concentrated in the synaptic cleft of neuromuscular junctions in rays. In the studies described here we made additional monoclonal antibodies against agrin and used them to extend our knowledge of agrin-like molecules at the neuromuscular junction. We found that anti-agrin antibodies intensely stained the synaptic cleft of frog and chicken as well as that of rays, that denervation of frog muscle resulted in a reduction in staining at the neuromuscular junction, and that the synaptic basal lamina in frog could be stained weeks after degeneration of all cellular components of the neuromuscular junction. We also describe anti-agrin staining in nonjunctional regions of muscle. We conclude the following: (a) agrin-like molecules are likely to be common to all vertebrate neuromuscular junctions; (b) the long-term maintenance of such molecules at the junction is nerve dependent; (c) the molecules are, indeed, a component of the synaptic basal lamina; and (d) they, like the molecules that direct the formation of receptor and esterase aggregates on regenerating myofibers, remain associated with the synaptic basal lamina after muscle damage.
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PMID:Agrin-like molecules at synaptic sites in normal, denervated, and damaged skeletal muscles. 282 88

The portion of the muscle fibre's basal lamina that occupies the synaptic cleft at the neuromuscular junction contains molecules that cause the aggregation of acetylcholine receptors and acetylcholinesterase on regenerating muscle fibres. Agrin, which is extracted from basal lamina-containing fractions of the Torpedo electric organ and causes the formation of acetylcholine receptor and acetylcholinesterase aggregates on cultured myotubes, may be similar, if not identical, to the acetylcholine receptor- and acetylcholinesterase-aggregating molecules at the neuro-muscular junction. Here we summarize experiments which led to the identification of agrin and established that the basal lamina at the neuromuscular junction contains molecules antigenically similar to agrin. We also discuss results which raise the possibility that agrin-like molecules at the neuromuscular junction are produced by motor neurones.
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PMID:Identification of agrin in electric organ extracts and localization of agrin-like molecules in muscle and central nervous system. 282 10

Agrin, a protein extracted from the electric organ of Torpedo californica, induces the formation of specializations on cultured chick myotubes that resemble the postsynaptic apparatus at the neuromuscular junction. The aim of the studies reported here was to characterize the effects of agrin on the distribution of acetylcholine receptors (AChRs) and cholinesterase as a step toward determining agrin's mechanism of action. When agrin was added to the medium bathing chick myotubes small (less than 4 micron 2) aggregates of AChRs began to appear within 2 h and increased rapidly in number until 4 h. Over the next 12-20 h the number of aggregates per myotube decreased as the mean size of each aggregate increased to approximately 15 micron 2. The accumulation of AChRs into agrin-induced aggregates occurred primarily by lateral migration of AChRs already in the myotube plasma membrane at the time agrin was added to the cultures. Aggregates of AChRs and cholinesterase remained as long as agrin was present in the medium; if agrin was removed the number of aggregates declined slowly. The formation and maintenance of agrin-induced AChR aggregates required Ca++, Co++ and Mn++ inhibited agrin-induced AChR aggregation and increased the rate of aggregate dispersal. Mg++ and Sr++ could not substitute for Ca++. Agrin-induced receptor aggregation also was inhibited by phorbol 12-myristate 13-acetate, an activator of protein kinase C, and by inhibitors of energy metabolism. The similarities between agrin's effects on cultured myotubes and events that occur during formation of neuromuscular junctions support the hypothesis that axon terminals release molecules similar to agrin that induce the differentiation of the postsynaptic apparatus.
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PMID:Regulation of agrin-induced acetylcholine receptor aggregation by Ca++ and phorbol ester. 283 19

We have examined the variation in receptor density and area among neurite-associated acetylcholine receptor patches (NARPs) induced by chick ciliary ganglion neurons on nearby myotubes in vitro. Quantitative analysis of rhodamine-alpha-bungarotoxin (RBTX) NARPs revealed that about 15% of the NARPs were "outstanding" in terms of size (greater than 60 micron 2) and fluorescence intensity (greater than 100 units on a 0-255 scale). The total number of receptors at different NARPs ranged over 3 orders of magnitude. It is likely that variation in NARP size and intensity reflects regional variation in the ability of myotubes to respond to the neuronal influence because (1) no gradient in NARP size or intensity with distance from the soma was evident; (2) the intensities and areas of uninnervated receptor clusters (hot spots) were similar to those of NARPs; (3) acetylcholinesterase was present at the same proportion of hot spots and NARPs at all times examined. We found no physiological or morphological evidence that outstanding NARPs were more effective sites of transmitter release. Outstanding NARPs were restricted to the longest neurite of individual neurons, so they may signal trophic interactions of the sort that promote neurite outgrowth and survival.
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PMID:Variation among acetylcholine receptor clusters induced by ciliary ganglion neurons in vitro. 284 86

Molecules antigenically similar to agrin, a protein extracted from the electric organ of Torpedo californica, are highly concentrated in the synaptic basal lamina of neuromuscular junctions in vertebrate skeletal muscle. On the basis of several lines of evidence it has been proposed that agrin-like molecules mediate the nerve-induced formation of acetylcholine receptor (AChR) and acetylcholinesterase (AChE) aggregates on the surface of muscle fibers at developing and regenerating neuromuscular junctions and that they help maintain these postsynaptic specializations in the adult. Here we show that anti-agrin monoclonal antibodies selectively stain the cell bodies of motor neurons in embryos and adults, and that the stain is concentrated in the Golgi apparatus. We also present evidence that motor neurons in both embryos and adults contain molecules that cause the formation of AChR and AChE aggregates on cultured myotubes and that these AChR/AChE-aggregating molecules are antigenically similar to agrin. These findings are consistent with the hypothesis that agrin-like molecules are synthesized by motor neurons, and are released from their axon terminals to become incorporated into the synaptic basal lamina where they direct the formation of synapses during development and regeneration.
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PMID:Motor neurons contain agrin-like molecules. 284 87

The effects of denervation and of direct electrical stimulation of denervated muscle upon the acetylcholine receptor (AChR) clusters and acetylcholinesterase (AChE) spots in the fast avian muscle posterior latissimus dorsi have been investigated. Denervation at day 2 after hatching leads to a disappearance of the junctional AChR clusters and to a marked decrease of AChE spots. Direct electrical stimulation of denervated muscle allows the maintenance of AChR clusters and partly prevents the loss of AChE spots. When AChR cluster and post-synaptic AChE have disappeared in a denervated muscle, muscle activity induced by direct stimulation is unable to induce their accumulation.
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PMID:Effects of denervation and direct electrical stimulation upon acetylcholine receptors and acetylcholinesterase accumulation in developing latissimus dorsi muscle of the chick. 295 9

We performed comparative biochemical and morphological studies of trembler and control soleus muscles. In the mutant, small multiple endplates were observed on some muscle fibers. The acetylcholine receptor (AChR) concentration and the acetylcholinesterase (AChE) activity of the muscle were not modified in the mutant. Our results suggest that both AChR and AChE levels are similar in trembler and control soleus but that these molecules are localized differently in the sarcolemma of the mutant muscles.
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PMID:Acetylcholine receptors and acetylcholinesterase activity in soleus muscle of trembler dysmyelinating mutant: a cytochemical and biochemical analysis. 301 Jan 96

The development of miniature end-plate currents (m.e.p.c.s) was studied in the superior oblique and interhyoideus muscles of Xenopus laevis. An analysis of m.e.p.c. decays shows that each muscle possesses its own characteristic programme of end-plate current development. In the superior oblique, the exponential decay constants of m.e.p.c.s were initially about 3 ms; they declined within half a day to 1 ms and remained at that value for six weeks. They then gradually became longer, reaching a mean value of 1.7 ms at late metamorphosis. In the interhyoideus, m.e.p.c. decay constants were initially about 6 ms. They declined in less than one day to a mean value of 2.6 ms and remained there for the following seven weeks. Upon completion of metamorphosis, the decay constants underwent a further decrease to about 1 ms. In both muscles, the changes in m.e.p.c. decays were correlated with developmental changes in muscle contraction speeds, as measured by maximum twitch frequencies. The above changes in end-plate currents in the superior oblique and interhyoideus muscles are discussed in terms of the development of acetylcholine receptor channel gating and acetylcholinesterase activity.
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PMID:Comparative development of end-plate currents in two muscles of Xenopus laevis. 301 34

Miniature end-plate potentials (MEPPs) are increased in size by pretreatment in a hypertonic Ringer. This paper is about the treatments that increase quantal size and the evidence that it occurs by packing more acetylcholine (ACh) in the quanta. Sartorius muscles were soaked for 2 h in a hypertonic Ringer, containing 200 mM NaCl in place of the usual 120 mM, and then returned to Ringer. In the hypertonic solution the miniature frequency was above 100/s. The treatment increased the size of the miniatures, recorded with an intracellular electrode after the return to usual Ringer, by a factor of approximately 2.5, compared with paired muscles kept in usual Ringer throughout. When the hypertonic solution was made with 200 mM sodium gluconate, after the return to usual Ringer, the miniatures increased in size by a factor of approximately 3.6. The large miniatures produced by the treatment fit a log normal probability distribution function, except for a variable small fraction of the largest events that may represent multiple releases. Miniatures recorded from untreated end plates fit better to a log normal distribution function than to a normal distribution function. The effects of the hypertonic treatments on the acetylcholine receptor (AChR) were accessed by measuring, after the return to usual Ringer, ACh noise, alpha-bungarotoxin binding, and the reversal potential. None of these measurements revealed significant differences between experimental and control preparations. The increases occurred when neostigmine was present in the hypertonic and usual solutions and when it was not, so changes in acetylcholinesterase (AChE) do not appear to be involved. Both the MEPPs and miniature end-plate currents, recorded with the two electrode voltage clamp, increased in size, so the increase is not owing to an rise in the input resistance of the muscle fiber. The increase in quantal size was prevented by including 1-10 microM AH5183 in the hypertonic solution. This drug blocks ACh uptake into synaptic vesicles. Therefore, it seems likely that the treatments act by increasing the quantity of ACh/quantum. Cyclohexamide (10 micrograms/ml), an inhibitor of protein synthesis, did not affect the increase in size caused by hypertonic solutions. Size increases were detected after 15 min in hypertonic solution. Most of the increase was complete after 1 h and there was no further increase after 2 h.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pretreatment with hypertonic solutions increases quantal size at the frog neuromuscular junction. 303 13


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