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)

Adult male rats were subjected to 4 weeks' respiratory treatment with n-hexane (5000 ppm, 16h/day, 6 days/week); motor conduction velocity was significantly decreased in tail nerves at all weekly intervals and did not approach normal values in the 4 weeks following interruption of treatment. Plasma acetylcholinesterase (AChE) levels were significantly increased at all weekly intervals during treatment (25-40%); 2 weeks after the end of treatment they had returned to baseline. Oral treatment with 2,5-hexanedione (HD) (1% in drinking water) caused a similar increase in plasma levels; this increase was statistically significant also when compared with pair-fed (PF) control rats. A sucrose density gradient analysis showed only one peak of AChE activity at approximately 10 S (as in normal plasma). The levels of butyrylcholinesterase were unaltered in plasma of both n-hexane-and HD-treated rats. Both the fast-contracting EDL and the slow-contracting soleus muscles lost weight in HD-treated rats with respect to free-fed (AL) and PF controls. AChE levels responded differently to HD treatment in the two muscle types: in EDL total extracts, AChE activity increased considerably with respect to AL controls (+ 70%, p less than 0.001), while the levels of the 16 S and 4 S molecular forms were unaltered. The increased levels of AChE found in plasma of rats intoxicated with n-hexane or with its metabolite HD may originate from muscle and correspond to an increased secretion of this molecular form.
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PMID:Cholinesterases in blood plasma and tissues of rats treated with n-hexane or with its neurotoxic metabolite 2,5-hexanedione. 343 86

Molecular forms and histochemical localization of acetylcholinesterase and nonspecific cholinesterase were analysed in muscle regenerates obtained from rat EDL and soleus muscles after ischaemic-toxic degeneration and irreversible inhibition of preexistent enzymes. Regenerating myotubes and myofibres produce the 16S AChE form in the absence of innervation. The 10S AChE form prevails over 4S form with maturation into striated fibres. Although the patterns of AChE molecular forms in normal EDL and soleus muscles differ significantly no such differences were observed in noninnervated regenerates from both muscles. Two types of focal accumulation of AChE appear on the sarcolemma of regenerating muscles: first, in places of former motor endplates and, second, in extra-junctional regions. The 4S form of nonspecific cholinesterase is prevailing in regenerating myotubes whereas its asymmetric forms or focal accumulations could not be identified reliably. The satellite cells which survive after muscle degeneration probably originate from some type of late myoblasts and transmit the information concerning the ability to synthesize the asymmetric AChE forms and to focally accumulate AChE to regenerating muscle cells. Synaptic basal lamina from former motor endplates may locally induce AChE accumulations in regenerating muscles.
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PMID:Molecular forms and localization of acetylcholinesterase and nonspecific cholinesterase in regenerating skeletal muscles. 357 93

The objective of this investigation was to determine the distribution of cholinergic (acetyl-cholinesterase, AChE) and noncholinergic markers in slow-, fast-, and mixed-fiber containing muscles (soleus, SOL; extensor digitorum longus, EDL; and diaphragm, DIA, respectively). Noncholinergic markers included high-energy phosphates (adenosine triphosphate, ATP; phosphocreatine, PCr; and their metabolites), and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) and their isoenzymes and subforms. All three types of muscles had only one CK isoenzyme, CK-MM, which totally consisted of MM3 subform. Levels of these determinants were highest in EDL followed by DIA and least in SOL. Another objective was to determine alterations of these markers under the influence of acute carbofuran (1.5 mg/kg) or methyl parathion (MPTH, 5 mg/kg) toxicity. Rats receiving either insecticide showed cholinergic signs with maximal severity including muscle fasciculations and convulsions within 15-30 min that lasted for about 2 h. At 1 h postinsecticide injection, when AChE was maximally inhibited (81-96%), significant depletion of ATP and PCr was evident in muscles (DIA > SOL > EDL), and activities of CK-MM and LDH were elevated in muscles and consequently in serum. Serum CK-MM3 activity was markedly reduced with sequential increase in MM2 and MM1 subforms, probably due to induced higher carboxypeptidase activity. These findings suggested that (1) the differences in levels of biochemical constituents in muscles depend upon the fiber type, (2) anticholinesterase insecticide-induced increased muscle activity produces characteristic changes in CK and LDH isoenzymes patterns, and (3) leakage of these enzymes/isoenzymes into serum is due to depletion of ATP and PCr, which are required to maintain the cell membrane permeability.
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PMID:Cholinergic and noncholinergic changes in skeletal muscles by carbofuran and methyl parathion. 796 39

The role of motor innervation in supporting and regulating muscle development was studied using aneural muscles in the hindlimb of the mouse mutant peroneal muscular atrophy (pma). This is a single-locus autosomal mutation where homozygous animals lack the common peroneal nerve, so that muscles in the anterolateral compartment of the lower leg develop entirely without innervation. In adults, these muscles are extremely atrophied, and the mice display a clubfoot deformity. The mutant animals provide a preparation in which aspects of muscle formation can be studied in muscles that have never been exposed to direct contact with somatic motor or sensory axons, without pharmacological or surgical intervention. Using quantitative electron microscopy, we found that normal numbers of primary myotubes formed in aneural pma EDL muscles, but a greater than normal proportion degenerated during the first 2 days after their formation. Secondary myotubes appeared at their normal time and position within the muscle, initially in normal numbers, so that the ratio of secondary to primary myotubes initially was greater in pma than in CF1 control strain mice. No abnormalities in ultrastructure were seen until the time of birth, when retardation in development was obvious, together with invading macrophages and degenerating myofibres. The results show that secondary myotube formation in the mouse, as in the chick (B. J. Fredette and L. T. Landmesser, Dev. Biol. 143, 19-35, 1991) is not directly dependent on innervation. In control muscles, secondary myotubes first form in the vicinity of endplates on primary myotubes. No aggregations of ACh receptors or acetylcholinesterase were present in the aneural muscles, showing that these are neurally induced in the mouse, but secondary myotubes formed in their normal position indicating that positional information related to endplate formation is present in aneural muscles.
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PMID:Formation of primary and secondary myotubes in aneural muscles in the mouse mutant peroneal muscular atrophy. 846 48

RGTA11 is a chemically substituted dextran that mimics some of the properties of heparin or heparan sulphates towards heparin binding growth factors as well as inhibits some heparin binding proteases. In vivo RGTA11 has been shown to enhance muscle regeneration after crush. We now present evidence that RGTA11 can alos favour reinnervation of fast (EDL) as well as slow (soleus) crushed muscles. Both types of muscles were injected with RGTA11 after crushing and nerve cutting. In EDL muscles, after 16 days, motor end plates were more rapidly reformed and choline acetyl-transferase activity was 2 fold higher than in controls. In soleus muscles, after 16 days, motor end plates were reformed at normal size while controls were on average 30% smaller, the 16S form of acetyl-cholinesterase and choline acetyl-transferase activity were twice those of non injected regenerating controls. In conclusion, RGTA11 favours axonal growth and synaptic differentiation, allowing a more rapid reinnervation and maturation of the regenerated fibers. RGTA may present a new family of drugs against neuromuscular degenerescence.
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PMID:[Effects of substituted dextran on reinnervation of a skeletal muscle in adult rats during regeneration]. 855 49

The influence of mechanical load on the levels of acetylcholinesterase (AChE) mRNA was studied in order to examine to which extent different loading conditions may be responsible for differences in AChE regulation between the soleus, which is an antigravity muscle, and the fast EDL muscle. Forty-eight female rats were randomly assigned to three groups: a group with hindlimb suspension producing soleus muscle unloading, a group with ablation of synergistic gastrocnemius muscle causing overload of the soleus muscle, and the control group. The soleus muscles were isolated after 8 days of treatment AChE mRNA levels were analyzed by Northern blots and evaluated densitometrically. The values were normalized with beta-actin mRNA level, and then a value of 100% was assigned to the mRNA level in the control EDL muscle. Muscle unloading did not produce a significant increase of the AChE transcript levels, but the levels were rather variable. However, a statistically significant increase of AChE mRNA levels was observed in overloaded soleus muscles. These results corroborate the hypothesis that the slow and fast patterns of activity appear more important then muscle loading for the differences in regulation of AChE mRNA levels in fast and slow muscles.
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PMID:Effect of mechanical load on acetylcholinesterase mRNA levels in the slow soleus muscle of the rat. 1100 34

Acute toxic effects of acetylcholinesterase (AChE) inhibitors on skeletal muscles are thought to involve oxidative stress with increased generation of free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Muscle hyperactivity with its increased oxygen and energy consumption appear to be the primary cause of oxidative stress. The present investigation was therefore undertaken to establish the normal levels of F(2)-isoprostanes (F(2)-IsoPs, specific markers of ROS/oxidative stress), citrulline (determinant of NO/NOS and marker of RNS), and high-energy phosphates (HEP: adenosine triphosphate, ATP and phosphocreatine, PCr) in slow (soleus) and fast (extensor digitorum longus, EDL) muscles of rats. In addition, we aimed to determine if memantine HCl (MEM), in combination with atropine sulfate (ATS), prevents carbofuran-induced changes in markers of oxidative stress. Control values were not significantly different for F(2)-IsoPs (1.142 +/- 0.027 and 1.177 +/- 0.092 ng/g) and citrulline (469.7 +/- 31.8 and 417.8 +/- 18.5 nmol/g) in soleus and EDL muscles, while the values were different for HEP (ATP, 3.66 +/- 0.11 and 5.85 +/- 0.14 micromol/g; PCr, 7.91 +/- 0.26 and 13.14 +/- 0.31 micromol/g). Rats acutely intoxicated with carbofuran (1.5 mg/kg, s.c.) showed the signs of maximal toxicity including muscle hyperactivity within 60 min of exposure. At this time, F(2)-IsoPs (177 and 153%) and citrulline (267 and 304%) levels were significantly increased, while ATP (46 and 43%) and PCr (44 and 46%) levels were decreased in soleus and EDL, respectively. Rats pretreated with MEM (18 mg/kg, s.c.) and ATS (16 mg/kg, s.c.), 60 and 15 min prior to carbofuran, respectively, showed no signs of toxicity. MEM in combination with ATS protected muscles from carbofuran-induced hyperactivity and attenuated increases in F(2)-IsoPs and citrulline, and depletion of HEP. Carbofuran-induced changes and protection by MEM and ATS were of similar magnitude in both muscles. These findings indicate that carbofuran-induced muscle hyperactivity produces oxidative stress as measured by increased ROS and RNS generation, and HEP depletion. MEM and ATS prevent the carbofuran-induced chain of events involved in oxidative stress.
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PMID:Carbofuran-induced oxidative stress in slow and fast skeletal muscles: prevention by memantine and atropine. 1566 29

We have investigated effect of a representative of the novel class of selective acetylcholinesterase inhibitors A 1,3-bis[5(diethyl-o-nitrobenzyl ammonio) penthyl]-6-methyluracildibromide (compound 547) on duration and rhythm of sequence of right atrial action potential (AP) as well as on kinetics of acetylcholinesterase catalyzed reaction in homogenates of skeletal muscle (m. extensor digitorum longus) and cardiac muscle in the rat. We have shown that contrary to classical acetylcholinesterase inhibitors armin and proserin none of studied concentrations (1, 10 and 100 nM) of compound 547 exerted significant effect on AP configuration and rate of sinus rhythm. Compound 547 belongs to noncompetitive type with K1(heart)=3.6 x 10(-4) M and K1(EDL)=1.3 x 10(-8) M. Proserin exerts comparable inhibitory action on reaction in the heart and skeletal muscle, its K1(heart)=0.73 x 10(-5) M and K1(EDL) = 0.4 x 10(-5) M. Thus low sensitivity of myocardium to compound 547 in electrophysiological experiments is not related to lesser availability of synaptic acetylcholinesterase in the heart compared with acetylcholinesterase in skeletal muscles but reaction catalyzed by cardiac acetylcholinesterase is actually to a substantial degree less prone to inhibition by compound 547.
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PMID:[The study of effects of a novel acetylcholinesterase inhibitor on electrical activity of the heart]. 1916 1

We undertook a longitudinal study of the histological and biochemical changes at the neuromuscular junction (NMJ) in muscles of SOD1-G93A mice. We also assessed these functions in mice treated with a known heat shock protein inducer, arimoclomol. Tissue samples of treated and untreated mSOD mice were analysed for AChE and ChAT enzyme activities as markers of neuromuscular function. Sections of hindlimb muscles (TA, EDL and soleus) were also stained for succinate dehydrogenase and silver cholinesterase activities as well as for immunohistochemistry. Hsp70 levels were also measured from muscle samples using ELISA. Results showed that denervation and nerve sprouting were present at symptom onset in fast muscles, although slow muscles remained fully innervated. Cholinergic enzyme activities were reduced prior to denervation and declined further with disease progression. Reduction of endplate size, a slow to fast shift in muscle phenotype was also observed. Treatment with arimoclomol delayed the appearance of these changes, increased innervation, cholinergic enzyme activities and endplate size and reversed muscle fibre transformation. These beneficial effects of arimoclomol in muscles were accompanied by an increase in Hsp70 expression. In conclusion, our results indicate that pharmacological targeting of muscles at early stages of disease may be a successful strategy to ameliorate disease progression in ALS.
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PMID:Treatment with a coinducer of the heat shock response delays muscle denervation in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. 2259 Nov 94

The influence of mechanical load on the levels of acetylcholinesterase (AChE) mRNA was studied in order to examine to which extent different loading conditions may be responsible for differences in AChE regulation between the soleus, which is an antigravity muscle, and the fast EDL muscle. Forty-eight female rats were randomly assigned to three groups: a group with hindlimb suspension producing soleus muscle unloading, a group with ablation of synergistic gastrocnemius muscle causing overload of the soleus muscle, and the control group. The soleus muscles were isolated after 8 days of treatment. AChE mRNA levels were analyzed by Northern blots and evaluated densitometrically. The values were normalized with beta-actin mRNA level, and then a value of 100% was assigned to the mRNA level in the control EDL muscle. Muscle unloading did not produce a significant increase of the AChE transcript levels, but the levels were rather variable. However, a statistically significant increase of AChE mRNA levels was observed in overloaded soleus muscles. These results corroborate the hypothesis that the slow and fast patterns of activity appear more important then muscle loading for the differences in regulation of AChE mRNA levels in fast and slow muscles.
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PMID:Effect of mechanical load on acetylcholinesterase mRNA levels in the slow soleus muscle of the rat. 2800 3


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