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)

There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer's disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age 65-75 years) and 15 AD patients (age 61-78 years), we studied the effects of both pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic somatostatin, on GH response to GHRH (1 microgram/kg i.v.). The GH response to PD alone was also studied. Twenty-two young healthy volunteers were studied as control group. Basal GH levels were similar in young, elderly and AD subjects (0.7 +/- 0.2, 0.8 +/- 0.2 and 0.9 +/- 0.2 microgram/l). IGF-I levels were lower (p < 0.005) in elderly (73.9 +/- 8.2 microgram/l) and in AD subjects (108.0 +/- 5.9 micrograms/l) than in young subjects (288.7 +/- 22.1 micrograms/l); however, they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD-induced GH release did not significantly differ in young, elderly and AD subjects while the GH responses to GHRH in the elderly (AUC: 297.9 +/- 49.2 micrograms/l) and in AD subjects (437.6 +/- 93.5 micrograms/l/h) were lower (p < 0.01) than in young subjects (658.6 +/- 100.1 micrograms/l/h). PD potentiated the GH response to GHRH both in elderly and in AD subjects (901.7 +/- 222.4 and 1,070.3 +/- 207.2 micrograms/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those recorded in young subjects (2,041.1 +/- 245.6 micrograms/l/h).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone secretion in Alzheimer's disease: studies with growth hormone-releasing hormone alone and combined with pyridostigmine or arginine. 813 94

Dendroaspis angusticeps (green mamba) has two toxins, fasciculins, that are non-competitive inhibitors of acetylcholinesterase. Amino groups of fasciculin 2 were acetylated with acetic anhydride. The monoacetyl derivatives of the epsilon-amino groups (Lys 25, 32, 51 and 58) retained between 28 and 43% of the initial activity and that of the alpha-amino group 72%. Acetylation of Lys 25 that has the most reactive amino group decreased the activity by 65% apparently without producing structural perturbations, since the circular dichroism spectrum was not affected. The three-dimensional structure shows a cationic cluster formed by Lys 32, 51, Arg 24 and 28. A comparison of 175 sequences of homologous toxins shows that Lys 32 is unique for fasciculin. Acetylation of lysine residues in the cluster had a large effect and reduced the activity by 72% (Lys 32) and 57% (Lys 51). This suggests an important role for the cationic cluster. Lys 25 together with Lys 32 and 51 were, therefore, assumed to be in the active site.
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PMID:Study of structure-activity relationship of fasciculin by acetylation of amino groups. 828 Jul 46

1. The AVP-like insect diuretic hormone is a biologically active antiparallel dimer present, along with its non-active monomeric form (Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-GlyNH2), in the African locust. 2. It exhibits diuretic activity by increasing fluid excretion at the level of the Malpighian tubules. 3. To date, both monomer and dimer have been assayed using a radioimmunoassay originally prepared for mammalian AVP. 4. We have developed here an original enzyme immunoassay based on the use of antibodies to insect AVP-like raised in rabbits against synthetic monomers and dimers, using acetylcholinesterase conjugate as an enzymatic tracer. 5. This enzyme immunoassay enables measurement of the dimer to be made with adequate sensitivity (0.3 nmol/l, i.e. 21 pg/well) and reproducibility while sensitivity of the monomer is somewhat lower (14 nmol/l, i.e. 480 pg/well). 6. The assay was validated by assaying native dimer and monomer throughout the different steps of purification (from a crude extract to reversed-phase liquid chromatographic fractions). 7. A good correlation was observed between radioimmunoassays and enzyme immunoassays. 8. The enzyme immunoassay was also used to measure the level of AVP-like peptides in several insect tissues not explored to date.
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PMID:Development of an enzyme immunoassay for arginine-vasopressin (AVP)-like insect diuretic hormone. 828 61

Human and rabbit paraoxonases/arylesterases were purified to homogeneity by chromatographic and gel electrophoretic/isofocusing procedures coupled with activity stains. N-terminal and peptide sequence analysis suggested retention of the secretion signal sequence and allowed design of oligonucleotide probes. The probes were used to isolate a 1294-bp rabbit paraoxonase cDNA clone, which, in turn, was used to isolate three human cDNA clones. Comparison of rabbit and human protein and cDNA sequences indicated a high degree of sequence conservation (approximately 85% identity) and verified that paraoxonase retains its signal sequence (except for the N-terminal Met). The rabbit cDNA encodes a protein of 359 amino acids and the human a protein of 355 amino acids. In situ hybridization demonstrated, as expected, that the paraoxonase gene maps to the long arm of human chromosome 7. Arginine at position 192 specifies high activity paraoxonase and glutamine low activity human paraoxonase. Variation in protein levels explains the variation of enzyme activity observed within a genetic class. Toxicity studies showed that raising rat plasma paraoxonase levels by i.v. administration of partially purified rabbit paraoxonase protected animals against cholinesterase inhibition by paraoxon and chlorpyrifos oxon. Protection correlated with the relative rates of hydrolysis of these two compounds.
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PMID:Human and rabbit paraoxonases: purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification. 839 45

Acetylcholinesterase (AcChE, EC 3.1.1.7) was isolated from the electric organ of T. nobiliana and treated with the active-site-directed alkylating agent 1-bromo-2-[14C]pinacolone ([14C]BrPin), or with BrPin, which acts initially as a competitive inhibitor, Ki = 0.18 mM, and then inactivates the enzyme, k2 = 1.8 x 10(-4) s-1. AcChE aliquots were digested with trypsin and fractionated by reversed phase high performance liquid chromatography. Inactivation caused a decrease in one absorption peak and an increase in another, identified as the peptide beginning at Ala-222 and extending to Arg-242. 5-Trimethylammonio-2-pentanone, a competitive inhibitor, isosteric with acetylcholine, retarded the inactivation and decreased the quantity of labeled peptide. On sequencing, the 14C label was found associated with Cys-231. This was confirmed by comparison with synthesized S-pinacolonylcysteine, by study of effects of blocking the sequencing by o-phthalaldehyde, and by inactivation by 2,2'-dipyridyl disulfide (2-PDS), a thiol-specific reagent that acts initially as a competitive inhibitor, Ki = 0.042 mM, and then inactivates the enzyme, k2 = 5.0 x 10(-4) s-1. This is retarded by 5-trimethylammonio-2-pentanone, and prior inactivation by 2-PDS prevents subsequent reaction of [14C]BrPin in the active site. BrPin inactivates AcChEs from Electrophorus electricus and from human erythrocyte, but 2-PDS does not. Neither reagent inactivates butyrylcholinesterases from human and horse serum.
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PMID:Labeling of cysteine 231 in acetylcholinesterase from Torpedo nobiliana by the active-site directed reagent, 1-bromo-2-[14C] pinacolone. Effects of 2,2'-dipyridyl disulfide and other sulfhydryl reagents. 841 33

People with genetic variants of cholinesterase (ChE) have been reported to have prolonged apnea with the use of myorelaxant succinylcholine. For the silent type variant ChE, two cases of mutation have been reported. In one case, the exon 2 of ChE gene was disrupted by a 342 bp insertion of Alu element. In the other case, a frame shift mutation was identified at Gly-117 (GGT-->GGAG) to create a stop codon at nucleotide 384. Dibucaine resistant ChE was examined and found to have a point mutation at nucleotide 209 (A-->G) that converted Asp-70 to Gly, and consequently reduced the affinity of ChE for choline esters. In addition, another two types of a point mutation reducing ChE activity were reported on K variant (Ala-539-->Thr) and a case of (Gly-365-->Arg) in a patient with liver cirrhosis.
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PMID:[Gene analysis of human cholinesterase variants]. 846 62

Monoclonal antibodies (mAbs) were raised against a peptide of the 10 C-terminal amino acids of human brain acetylcholinesterase (AChE): H-Tyr-Ser-Lys-Gln-Asp-Arg-Cys-Ser-Asp-Leu-OH. Two positive clones (mAbs 190-1 and 190-2) were selected and tested for their ability to distinguish between mammalian brain and erythrocyte AChEs. In a solid-phase enzyme antigen immunoassay as well as by Western- and dot-blot analysis, both antibodies showed clear binding to AChE from human and bovine brain but not to AChE from erythrocytes. MAbs 190-1 and 190-2 reacted with neither AChE from electric eel nor butyrylcholinesterase from human serum. Both antibodies were used in a quantitative assay for AChE in amniotic fluids, where AChE activity could be found only in samples from open neural tube-defect pregnancies, but not in fluids from normal pregnancies or in artificially blood-contaminated samples.
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PMID:Monoclonal antibodies against a C-terminal peptide of human brain acetylcholinesterase distinguish between erythrocyte and brain acetylcholinesterases. 856 26

The G2 form of butyrylcholinesterase (BChE) of mucosal cells of rat intestine is a rare amphiphilic species, which is related to class II of acetylcholinesterase. Preliminary work indicated that the enzyme can bind heparin and suggested particular properties as compared to other BChEs. Ionic properties of the G2 form BChE were studied with different ionic exchangers. Heparin-Sepharose chromatography, nondenaturing electrophoresis and sucrose gradient centrifugation were used to study heparin interaction with the G2 form BChE. The enzyme structure was modified with reagents that react specifically with amino groups (p-hydroxyphenylglyoxal and 2,4,6-trinitrobenzene sulfonic acid). The G2 form was not retained by DEAE-cellulose which was generally used to isolate BChE from human serum, but was completely bound by strong cation exchanger (Dowex 50). Heparin-Sepharose quantitatively retained the enzyme which was partially eluted only by charged compounds. Nondenaturing gel electrophoresis showed a reduction in enzyme migration with increasing concentrations of heparin and chondroitin sulfate, but not with heparan sulfate. Triton X-100 dissociated the G2 form into monomers but failed to reverse the association between the enzyme and heparin. Reagents specific to amino groups indicated that arginine and lysine residues were involved in this association. In summary, these studies demonstrate that the ionic properties of the G2 form BChE are involved in the binding with heparin. Our results rule out the possibility of amphiphilic interactions in the formation of heparin-enzyme complex and indicate that amino groups are predominately involved in this association.
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PMID:Electrostatic interactions of the butyrylcholinesterase dimer of mucosal cells of rat intestine with glycosaminoglycans. 869 3

To determine whether local cholinergic mechanisms evoke nitric oxide (NO)-mediated flow-induced vasorelaxation, canine coronary artery rings without endothelium were suspended beneath an organ chamber that contained a stainless steel tube and a femoral artery segment with endothelium. The rings were superfused at a basal rate of 1 ml/min with physiological salt solution that was bubbled with 95% O2-5% CO2 and maintained at 37 degrees C. They were stretched to optimal length and contracted with prostaglandin F 2 alpha (2 x 10(-6) M). When flow through the stainless steel tube (direct superfusion) was increased from the basal rate of 1 to 4 ml/min, coronary force did not change. Superfusion of the rings (n = 8) with effluent from the femoral segment (endothelial superfusion) at 4 ml/min to study flow-induced vasodilation caused a 67.3 +/- 10.8% relaxation. Treatment of the segment with the NO synthase blocker NG-monomethyl-L-arginine (10(-4) M) eliminated the relaxation seen during endothelial superfusion (P < 0.05 vs. control). Application of atropine (10(-6) M) to additional femoral segments (n = 8) abolished the coronary relaxation observed during endothelial superfusion at 1 ml/ min, and the flow-induced relaxation observed at 4 ml/min was reduced from 64 +/- 8.3 to 27 +/- 5.6% (P < 0.05 vs. control). In studies on additional segments and rings (n = 6), the flow-induced relaxations at 4 ml/min of endothelial superfusion were blunted from 86 +/- 10 to 28 +/- 13% after the segments were treated with acetylcholinesterase (0.00028 U/min for 20 min). These data indicate that basal- and flow-induced release of NO from the vascular endothelium can be mediated by local cholinergic mechanisms. It is possible that flow causes acetylcholine release from certain endothelial cells, which stimulates NO release from these cells or from neighboring endothelial cells.
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PMID:Local cholinergic mechanisms mediate nitric oxide-dependent flow-induced vasorelaxation in vitro. 877 18

Pontine cholinergic neurotransmission is known to play a key role in the regulation of rapid eye movement (REM) sleep and to contribute to state-dependent respiratory depression. Nitric oxide (NO) has been shown to alter the release of acetylcholine (ACh) in a number of brain regions, and previous studies indicate that NO may participate in the modulation of sleep/wake states. The present investigation tested the hypothesis that inhibition of NO synthase (NOS) within the medial pontine reticular formation (mPRF) of the unanesthetized cat would decrease ACh release, inhibit REM sleep, and prevent cholinergically mediated respiratory depression. Local NOS inhibition by microdialysis delivery of N(G)-nitro-L-arginine (NLA) significantly reduced ACh release in the cholinergic cell body region of the pedunculopontine tegmental nucleus and in the cholinoceptive mPRF. A second series of experiments demonstrated that mPRF microinjection of NLA significantly reduced the amount of REM sleep and the REM sleep-like state caused by mPRF injection of the acetylcholinesterase inhibitor neostigmine. Duration but not frequency of REM sleep epochs was significantly decreased by mPRF NLA administration. Injection of NLA into the mPRF before neostigmine injection also blocked the ability of neostigmine to decrease respiratory rate during the REM sleep-like state. Taken together, these findings suggest that mPRF NO contributes to the modulation of ACh release, REM sleep, and breathing.
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PMID:Pontine nitric oxide modulates acetylcholine release, rapid eye movement sleep generation, and respiratory rate. 898 99


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